J Physiol 595.

1 (2017) pp 11–27 11

TO P I C A L R E V I E W
Neuroscience

Cerebellar physiology: links between microcircuitry

properties and sensorimotor functions
Henrik Jörntell
Neural Basis of Sensorimotor Control, Department of Experimental Medical Science, Lund University, Sweden

Movement
command
The Journal of Physiology

Final
Sensory
sensorimotor
readout
command

Abstract Existing knowledge of the cerebellar microcircuitry structure and physiology allows
a rather detailed description of what it in itself can and cannot do. Combined with a known
mapping of different cerebellar regions to afferent systems and motor output target structures,
there are several constraints that can be used to describe how specific components of the cerebellar
microcircuitry may work during sensorimotor control. In fact, as described in this review, the
major factor that hampers further progress in understanding cerebellar function is the limited
insights into the circuitry-level function of the targeted motor output systems and the nature of
the information in the mossy fiber afferents. The cerebellar circuitry in itself is here summarized

Henrik Jörntell received his PhD degree in Neurophysiology from Lund University. He is currently employed as a senior
lecturer at Lund University where he heads the lab ‘Neural Basis for Sensorimotor Control’ at the Department of Experimental
Medical Science. His interests are the neurophysiological analysis of neuronal microcircuits involved in movement control,
spanning cerebellar, spinal, brainstem and neocortical circuitry as well as models of how these structures interact during
movement performance and motor learning.


C 2016 The Authors. The Journal of Physiology 
C 2016 The Physiological Society DOI: 10.1113/JP272769
12 H. Jörntell J Physiol 595.1

as a gigantic associative memory element, primarily consisting of the parallel fiber synapses,
whereas most other circuitry components, including the climbing fiber system, primarily has
the role of maintaining activity balance in the intracerebellar and extracerebellar circuitry. The
review explores the consistency of this novel interpretational framework with multiple diverse
observations at the synaptic and microcircuitry level within the cerebellum.
(Received 9 May 2016; accepted after revision 29 June 2016; first published online 8 July 2016)
Email: henrik.jorntell@med.lu.se

Abstract figure legend The cerebellar neuronal circuitry is here summarized as a gigantic associative memory, consisting
of multiple functional subunits working in parallel, by which useful contingencies between diverse types of information
can be stored. The sources of information are the multiple mossy fiber systems that inform the cerebellum about
original motor commands/motor plans and sensorimotor information at different levels of abstraction. The output of
each functional subunit of the cerebellum is refining the ongoing movement command by linking learnt appropriate
sensorimotor functions for the particular context or state. Because of its size, the memory element can house the
appropriate associations, translatable to synaptic weights, relevant for all contexts or states that the individual can be
expected to experience during a lifetime. It follows that a key component necessary to further improve our understanding
of cerebellar function is a precise knowledge of the types and formats of information that reaches the cerebellum via the
vast variety of mossy fiber pathways, a subject area that has long been neglected. In parallel, a large part of the cerebellar
circuitry is proposed to be devoted to regulating the activity balance in the circuitry. The set points of the balances are
internal to the cerebellar neuronal circuitry but influence the excitability of the extracerebellar motor structures so that
the drive on individual muscles, for example, is not exaggerated or fall below operative excitation level.

Abbreviations DCN, deep cerebellar nuclei; DSCT, dorsal spinocerebellar tract; LTD, long-term depression; LTP,
long-term potentiation; MLI, molecular layer interneuron; PC, Purkinje cell; SCT, spinocerebellar tract; SRCT,
spino-reticulocerebellar tract.

Introduction intertwined with the massive sensory feedback with which

Over the last 10–15 years, several foundations for how we
understand the function of the cerebellum have changed.
Apart from an overall scientific progress, in particular the
capacity in several labs to record from the smaller neuron
types in the cerebellar cortex in vivo, the birth of new
neuroscience methods to explore the cerebellum and the
development of theories of global network function have
contributed to these advances. In the cerebellum, as in
other brain structures, function is determined both by
the physiology of the cellular and synaptic elements and
the structure of the neuronal network, where the latter
is being shaped as a result of another neurophysiological
process, synaptic plasticity or learning. Therefore, these
two aspects will be the focus of this review. The review
will also have a bias towards the somatic sensorimotor
functions and less focus on eye and neck motor functions
and on higher order neocortical (‘mental’) functions. It
is assumed, however, that many principles described here
will apply also to the latter. The review will start with a
brief résumé of the connectivity structure at the macro-
and microcircuitry level of the cerebellum, present some
recent insights in the details of the connectivity structure
and physiology of the microcircuitry and then mainly
focus on cerebellar physiology in a wider functional sense,
including the constraints for cerebellar function imposed
by the systems that the cerebellum is connected with.
The motor control of the brain is assumed to be deeply
it is provided, and neural representations of sensorimotor
functions at different levels are the main platforms from
which this discussion takes its origin.
Before considering the physiology of the cerebellum
at a more detailed level it is important to be clear
about the mode of coding that is assumed. In contrast
to the original formulations in the classical ideas of
Marr–Albus, and many alternative theories, it is assumed
here that sparse coding, and other forms of coding
that depend on low firing rates and isolated spikes
generated with millisecond precision, do not apply. A
long range of theoretical arguments and experimental
observations support the idea that the cerebellum and
its afferent mossy fibre pathways instead operate using a
coding mode that is more reminiscent of dense code or
high-resolution, time-modulated rate code. These issues
have been extensively covered in a recent theoretical
paper (Spanne & Jörntell, 2015), but some of the
main arguments will be restated later in this review.
Changing the assumption with respect to the coding
away from sparse and spike-time dependent coding has
fundamental consequences for the functionality in the
cerebellar neuronal circuitry, not least with respect to
the crucial interplay between the Purkinje cells and the
neurons of the cerebellar nuclei. Similarly, cerebellar
contributions to ongoing movements can be explained
by simply considering high-resolution, time-modulated
rate code outputs in a population of Purkinje cells making


C 2016 The Authors. The Journal of Physiology 
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J Physiol 595.1 Cerebellar physiology 13

functionally specific connections to the cerebellar nuclear

neurons (Herzfeld et al. 2015). The behavioural control
by the cerebellar cortex can hence be explained without
A
considering synchrony in the activation of the Purkinje B
cells or climbing fibres, and potential effects of neural C1
C2
synchronization are therefore not considered here. C3

D1
Primary
fissure
Anatomical macro-organization helps understanding
of regional function
Midline
Beneath the largely regularly foliated surface of the Anterior lobe
cerebellum hides an intricate but repeatable neural Sagittal zones of the cerebellar cortex
connectivity pattern. The most useful feature with
which to understand the macro-organization of the A B C1 C2 C3 D1-DN
cerebellar neuronal network has proven to be the external
connections of the cortex, especially the climbing fibre
projections from the inferior olive to the cerebellar cortex Cerebellar
and the Purkinje cell projections from the cerebellar Fastigial Vestibular
Interpos. Interpos.
Lateral/dentate
and
posterior anterior vestibular
cortex to the cerebellar and vestibular nuclei. The sagittal nuclei
zonal divisions of the cortex that are defined by the
anatomical organization in these two connections, often
Cerebral cortex
referred to as the olivocerebellar and the corticonuclear
connectivity, have been reviewed many times, for many Corticospinal
species (Oscarsson, 1973, 1979; Armstrong, 1974; Voogd
& Glickstein, 1998; Apps & Garwicz, 2005), and will not
be reviewed in detail here. But from a physiological point
Reticulo- Vesticulo- Tecto- Rubro-
of view it is interesting to note that the olivocerebellar spinal spinal spinal spinal
and the corticonuclear connections may be examples
of genetically pre-programmed connectivity (Altman &
Bayer, 1997; Leto et al. 2015), which draws up the main line
of circuitry organization before other connections grow
in and distribute themselves according to the framework
established. For example, the distribution pattern of Spinal circuitry
Spinal cord
mossy fibres is closely related to that of the climbing grey matter
fibres (Pijpers et al. 2006; Ruigrok, 2011; Reeber et al.
2013), and experimental scrambling of the topographical
climbing fibre organization in the cortex is paralleled by Movement

a scrambling in the topography of the ingrowing mossy
fibres (Reeber et al. 2013). The zonal organization is likely
to be a universal anatomical-organizational feature of
the cerebellum across many species (Voogd & Glickstein,
1998).
The zonal connectivity structure defines a functional
structure. This was first described for the vermis and
intermediate part of the cerebellar anterior lobe, where
a number of sagittal zones could be defined solely on
the basis of by which spino-olivocerebellar pathways the
climbing fibres received their peripheral input (Oscarsson,
1973; Andersson & Eriksson, 1981). The specificity in
the corticonuclear connectivity (Voogd & Glickstein,
1998; Apps & Garwicz, 2005), where individual zones
target specific cerebellar or vestibular nuclei (Fig. 1), also
provides for a functional specificity of the output of the
zones. This is because specific nuclei target specific motor
Figure 1. Schematic illustration of the cerebellar sagittal
zonation and efferent connections
Upper panel, 3-D image of the anterior lobe of the cat cerebellum,
with zones in the vermis and the pars intermedia on one side of the
midline indicated. For clarity, the X and Y zones (Ekerot & Larson,
1982) are omitted from the display. DN indicates that there may be
multiple D zones not yet identified in the hemispheres of higher
animals such as primates. Lower panel, main output connections of
the cerebellar sagittal zones. The connections from the cortex to the
nuclei are well organized (Voogd & Bigaré, 1980; Trott & Armstrong,
1987a,b). For illustration purposes, only the main connections of the
output nuclei are indicated although some overlap in the targeted
motor structures may occur between them. All cerebellar nuclei also
target the neocortex via thalamic innervation. Connectivity based on
Hirai et al. (1982), Ito (1984), Gibson et al. (1987), Zwergal et al.
(2009) and Bostan et al. (2013). Targeted motor structures in turn
overlap in their innervation of the spinal interneuronal motor
circuitry (Jankowska, 1992; Bortoff & Strick, 1993; Hultborn, 2001;
Hammar et al. 2011; Jankowska et al. 2011a; Shrestha et al. 2012;
Spanne & Jörntell, 2013).


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14 H. Jörntell
systems in the brainstem (Ito, 1984), and to some extent
specific regions of the cerebral cortex via the thalamus
(Jörntell & Ekerot, 1999; Bostan et al. 2013). Hence,
although the general network structure within the cortex
follows the same basic plan across the cerebellum, the zonal
regions are likely to be primarily targeting specific motor
output systems in the brainstem. Regional localization
then becomes important as it can be expected that the
details of the connectivity within the cortex are locally
adapted to the specific control function of the motor
output system to which the zone is connected.
Whereas the macro-organization described above
mostly originates from work made decades ago, the
discovery that the expression of different molecular
markers such as aldolase C and excitatory amino acid
transporter 4 (EAAT4 ) are topographically congruent
with the sagittal zonal structure (Sugihara & Shinoda,
2004; Apps & Hawkes, 2009; Ruigrok, 2011; Reeber et al.
2013) suggest that a very fine molecular map parallels
the zonal functional structure. Under different names,
such as zebrins, these molecular markers are currently
emerging as a widely used tool for reference to localization.
As localization within the topographical structure has a
functional relevance (Fig. 1), it is a useful tool for the
physiologist.
The cerebellar cortical network as an adaptive
association layer
Most of the cerebellar information processing is carried
out by the main pathways of the cortical circuitry, which
were established almost 50 years ago (Eccles et al. 1967)
and mostly modified in the details over the years that
have passed since. They have been described numerous
times (Ito, 1984, 2006; Dean et al. 2010), and will only be
briefly summarized here. The main flow of information
in the cerebellar cortex is between the mossy fibres and
the Purkinje cells, where the mossy fibres make excitatory
synapses with granule cells, which in turn issue parallel
fibres that make excitatory synapses on the Purkinje cells.
The mossy fibre–granule cell information can also reach
the Purkinje cells as an inhibitory signal by means of the
parallel fibre synapses on the molecular layer interneurons
(MLIs; stellate and basket cells; Jörntell et al. 2010),
which in turn make inhibitory synapses on the Purkinje
cells. At least in regions involved in somatic sensori-
motor processing, these four types of neural elements can
be expected to carry out almost all of the information
processing that the cerebellar cortex is responsible for
during ongoing motor control, whereas in other regions
the unipolar brush cells may also be expected to contribute
(Dino et al. 1999).
Some recent studies have examined the properties of the
cortical intrinsic connections at a higher level of detail than
previously possible. A long-standing enigma has been the
J Physiol 595.1
physiology of the basket formation around the Purkinje
cell bodies, formed by the axon terminals of the basket
cells but also the stellate cells (Jörntell et al. 2010). It
seems clear that this formation does not form a regular
inhibitory synapse. Instead, it may rely on ‘ephaptic’ trans-
mission (Blot & Barbour, 2014), i.e. transmission of the
electrical field generated by the spike between closely
apposed neuronal membranes. How this non-regular form
of neuronal communication influences the mode of MLI
inhibition of Purkinje cells as a whole is not clear. However,
since the transmission of inhibitory inputs to Purkinje
cells in vivo in general appears to be smooth and without
rapid transients (Blazquez & Yakusheva, 2015), it seems
at the moment reasonable to assume that it does not
confer any functionally different effect compared to the
overall inhibitory signalling from MLIs. Other advances
include deepened insights into the rebound potentiation
of the MLI synapses on the Purkinje cells (Tanaka et al.
2013) and a more detailed decomposition of the molecular
components of this inhibitory connection (He et al. 2015).
A factor that has redefined how we understand the
intrinsic connectivity of the cerebellar cortex are the
findings of several forms of synaptic plasticity in addition
to the classical long-term depression (LTD) of the
parallel fibre synapses on Purkinje cells. In particular the
long-term potentiation (LTP) of parallel fibre synapses
on Purkinje cells and the LTP and LTD of parallel
fibre synapses on the molecular layer interneurons have
important consequences for the establishment of the
intrinsic connectivity of the cerebellum (Dean et al. 2010).
Whereas the firing behaviour of the individual neuron
types follow certain patterns, these plasticity mechanisms
can completely change the physiological ‘connectome’,
i.e. the patterns of synaptic weights between neurons.
Also other forms of plasticity in the cerebellar cortex
were described in the past decade. As discussed elsewhere
(Jörntell, 2016), the network position of these plasticity
effects do not have the same potential for functional
change as the parallel fibre synapses. They do, however,
have a natural position for maintaining the balance
of neuronal activity across the cerebellar network, as
discussed later.
Cerebellar nuclear neurons: inhibitory cortical output
integrated with excitatory drive
For all zones and functional regions of the cerebellum, the
relationship between the mossy fibre–granule cell-driven
Purkinje cell inhibition of the neurons of the deep
cerebellar nuclei (and relevant vestibular nuclei) and the
mossy fibre-driven excitation of the same neurons is a
critical step towards understanding cerebellar function
(Bengtsson & Jörntell, 2014). The Purkinje cells output
a time-varying inhibitory signal, defined by the cortical
processing, to the deep cerebellar nuclei (DCN). The

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J Physiol 595.1
balance between this inhibition, the intrinsic spontaneous
firing of the DCN neurons, and the time-varying
excitatory mossy fibre inputs to the DCN neurons
determines the cerebellar output. As there are many
Purkinje cells and many DCN neurons active under any
movement, there will be a spatiotemporal pattern of
Purkinje cell activation and a resulting spatiotemporal
pattern of DCN neuron output. Whereas the temporal
aspect of the Purkinje cell output pattern depends on the
processing in the cortex, its spatial distribution follows
not only the zonally specific topographical rule shown in
Fig. 1, but also the finer microzonal organization within
a zone is to some extent preserved in the connectivity
from the Purkinje cells to the cerebellar nuclear neurons
(Andersson & Oscarsson, 1978; Garwicz & Ekerot, 1994).
By using artificial inputs that synchronize the climbing
fibre activation of the Purkinje cells, this fine cortico-
nuclear organization can, in the experimental situation,
be used to identify the receptive field of the climbing
fibre input to the Purkinje cells that inhibits a particular
DCN cell (Andersson & Oscarsson, 1978; Bengtsson et al.
2011). This inhibitory climbing fibre receptive field, in
turn, is a functional tag for the DCN cell as it is indicative
of the type of movement it contributes to (Bengtsson &
Jörntell, 2014). In this experimental setting, the external
sources that drive the mossy fibre input to DCN cells show
some degree of relationship to those driving the climbing
fibre input (Bengtsson & Jörntell, 2014). Although a
comparatively weak relationship, its presence suggests
the involvement of synaptic plasticity also in shaping
the mossy fibre to DCN cell connection, possibly during
development, or also in adult life.
Whereas the above studies focused on the projection
neurons of the DCN, the cerebellar nuclei also contain
neurons that provide inhibitory feedback to the inferior
olive (Andersson et al. 1988; Chaumont et al. 2013)
as well as local inhibitory interneurons (Husson et al.
2014). The feedback control of the inferior olive by
the nucleo-olivary projection neurons provides a good
substrate for maintaining the overall activity balance
in the cerebellar cortex, as discussed below. The role
of the local, glycinergic inhibitory interneurons, and
the nucleo-cortical glycinergic neurons that innervate
primarily Golgi cells (Ankri et al. 2015), are less clear,
although a role in regulating overall activity balance lies
close at hand also for these neurons.
Mossy fibres carry most of the information used
in cerebellar processing
Among the two afferent systems to the cerebellar cortex
and the DCN, the mossy fibres exist in high numbers,
typically have a wide dynamic range of firing (Van Kan
et al. 1993; Garwicz et al. 1998; Jörntell & Ekerot, 2006;
Arenz et al. 2008; Prsa et al. 2009) and, due to their

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Cerebellar physiology 15
extensive branching (Wu et al. 1999; Quy et al. 2011),
each mossy fibre can potentially provide information to a
very high number of Purkinje cells. Although the climbing
fibres have a powerful effect on the Purkinje cell output,
their firing during behaviour typically does not reach
above 2 Hz, and since, for example, during a reaching
movement they fire less than once per movement (Horn
et al. 2004), they cannot carry a substantial amount of
information for the guidance of such movements. Hence, it
must be assumed that the mossy fibres are the main carriers
of information about ongoing movements and movement
commands to the cerebellum. Therefore to understand
the cerebellum a fundamental step is to understand the
nature of the information that is carried by the multitude
of mossy fibre systems.
Mossy fibre information defines cerebellar
microcircuitry function
What is the type of information that the cerebellum
would need, and what type of information can the central
nervous system provide? The answers to these questions
require detailed insights into how the brain operates
during movement, i.e. which sensorimotor circuitries are
engaged and what particular functions these circuitries
may have. In particular, one of the most difficult problems
in the analysis of any brain area is to understand how
information is represented in the system under study. It is
often implicitly assumed that the mode of representation
directly correlates with a particular set of arbitrary physical
parameters such as force, acceleration or skin indentation,
and that such parameters are coded for at the level of
each individual neuron. However, brain operation may be
organized using much more abstract representations of
the physical world. Whereas physical parameters may or
may not be explicitly represented in the peripheral sensors,
any central neuron will integrate this information with
internal brain representations. Hence, explicit neuronal
representation of any arbitrary physical parameter cannot
in general be expected to occur in central neurons, even
though correlations with such parameters may always be
possible to find. Instead, it is likely that any piece of
information represented in the brain is distributed across
a large set of neurons, and that each individual neuron
carries only bits and pieces of that information (Herzfeld
et al. 2015) at an abstracted level. Hence, the link between
the physical world and the neural abstractions thereof
needs to be understood.
Primarily since all subcortical sensorimotor systems
and all parts of the neocortex seem to be engaged under
movement, and therefore probably participate in the
representation of relevant sensorimotor information, at
least a number of basic constraints can be drawn. A
first essential principle is that because of the structure
of the nervous system, it is unlikely that a ‘pure’ motor
16 H. Jörntell J Physiol 595.1

A
Meissner (dorsal root ganglia)
Skin (Ab)
Merkel
Pacini
Hair follicle Primary sensory
signals

Tendon organ
(Ib)
(force sensor) Motor signals

Muscle spindle sensors (Ia)

(dynamic length)
Spinal interneuron
(II)
Spinal grey matter
Sensor activation

Motor nuclei
(α-motoneurons)
Movement

B
Cerebral cortex
Mossy fibres
Corticospinal
PCT
Pons
CCT
Rubrospinal
Tectospinal

Cun
Direct
path LRN
Reticulospinal
Vestibulospinal

DSCT

RSCT

*
VSCT

Figure 2. The sensorimotor circuitry of the brain and the spinocerebellar neurons
A, overview of peripheral and spinal circuitry being engaged during voluntary movement commands. B, some main
mossy fibre systems for somatic sensorimotor control. The connections from the spinal grey matter (outlined shape)
and brainstem nuclei of the spinocerebellar and spino-reticulocerebellar tracts/systems (SCT and SRCT, respectively)
as well as the connections of the cuneocerebellar and pontocerebellar systems are illustrated. Connectivity based
on Alstermark et al. (1981), Cheema et al. (1983), Kosinski et al. (1988), Ekerot (1990), Matsuyama & Drew
(1997), Jankowska et al. (2011a), Shrestha et al. (2012) and Geborek et al. (2013a). VSCT, ventral spinocerebellar
tract; DSCT, dorsal spinocerebellar tract; RSCT, rostral spinocerebellar tract; SRCT, spino-reticulocerebellar tract;
PCT, pontocerebellar tract; CCT, cuneocerebellar tract; Cun, main cuneate and external (accessory) cuneate nuclei;
LRN, lateral reticular nucleus; Pons, pontine nuclei. ∗ indicates that the VSCT pathway crosses the midline at the
spinal segmental level and then recrosses in the brainstem to enter the cerebellum ipsilaterally, which is omitted
in the illustration for clarity.


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J Physiol 595.1
command signal exists in the brain. This is because
any motor command that results in muscle activation
will inevitably also lead to sensory feedback (Fig. 2A)
that affects the activity of the motor output neurons at
all levels of the brain. Our bodies are equipped with
a very high-density sheet of sensors distributed across
skin, muscles, tendons and other connective tissue. These
sensors are the filter through which the brain ‘sees’ the
physical world. As even activation of a single muscle will
result in changes in tendon forces, muscle lengths and
skin strain patterns, it can be assumed that any kind
of movement will be accompanied by a very rich set
of sensor feedback patterns (Spanne & Jörntell, 2013).
Importantly, these sensor feedback patterns impinge on
spinal interneurons (Jankowska, 1992), which are also
the main final pathway of motor commands generated by
other structures of the brain (Santello et al. 2013). Hence,
the final motor command, i.e. the final spatiotemporal
structure of the activation of the α-motoneurons and
thereby the muscles, is a sum or a product of all the motor
command signals issued and the pattern of sensory feed-
back that they are associated with. For the cerebellum to
regulate ongoing movements, tapping off what is going
on in the population of spinal interneurons is a very
important source of information. This is precisely what
the numerous spinocerebellar pathways focus on.
Spinocerebellar pathways have their origin in the spinal
interneuron pool, and mediate combined sensory and
motor information (Fig. 2B). Some of the spinocerebellar
tract (SCT) neurons appear to be specialized neurons that
do not form part of the spinal interneuron circuitry but
sample information from the circuitry and project directly
to the cerebellum. An example of such an organization is
the Clarke’s column, containing neurons that form part
of the dorsal spinocerebellar tract (DSCT). However, a
more common principle appears to be that the neurons
that are part of a spinocerebellar system are also directly
participating in the spinal interneuronal circuitry, i.e.
some of the spinal interneurons not only form part of a
sensorimotor processing circuitry, they also send off axon
branches that travel all the way up to the cerebellum. Many
of the ventral spinocerebellar tract (VSCT) and rostral
spinocerebellar tract (RSCT) neurons seem to be of this
type. In fact, it is possible that even many DSCT neurons
fall into this category – a recently described pool of DSCT
neurons are located outside Clarke’s column and have
a location in the spinal grey matter that is no different
from that of regular spinal interneurons (Shrestha et al.
2012). A final category in this group of carriers of sensori-
motor information is the spino-reticulocerebellar tract
(SRCT). Similar to the spinocerebellar pathways, the SRCT
is made up of spinal interneurons that project towards the
cerebellum. However, rather than entering the cerebellum
directly, this pathway has an additional synaptic relay in the
lateral reticular nuclear neurons (Alstermark & Isa, 2012).

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Cerebellar physiology 17
SCT and SRCT neurons show a range of temporal
dynamics in their spike output pattern relative to an
ongoing movement (Arshavsky et al. 1978a,b; Fedirchuk
et al. 2013). That is, as a population they can
temporally signal the transitions between different phases
of movements, where each individual neuron can signal
one or several transitions. As they are driven in part by
inputs from specific sensors, the relationship between
their activation across different contexts or states (i.e.
different types of movements/phases of movements) will
follow certain patterns, as the activation of the sensors
are determined by the local biomechanics. Hence, each
SCT/SRCT neuron in principle describes a function
between a component of the motor command (sampled
from a variety of motor control structures; Oscarsson,
1973; Jankowska et al. 2011a; Shrestha et al. 2012) and
the resulting sensory feedback, and it can be expected
to do so across all possible motor contexts (Spanne &
Jörntell, 2013). But given the number of sensors in the
body and the number of ‘upper’ motoneurons, there are
so many possible functions that it is not reasonable to
assume that they are all represented in the brain (Spanne
& Jörntell, 2013). Instead, useful sensorimotor functions
could be laid out in the spinal sensorimotor circuitry from
early development, as an effect of early motor learning
(Spanne & Jörntell, 2013). Hence, the cerebellum is,
via the SCT/SRCT systems, provided with information
about ongoing activity in specific sensorimotor functions
and can, by specifically routing them through its inter-
nal network, primarily via plasticity in the molecular
layer, link specific functions to each other in specific
phase transitions and in specific states/motor contexts.
In other words, if the incoming mossy fibre information
is viewed as reflections of functions of sensorimotor
relationships approximated in extracerebellar circuitry,
then the pattern of connectivity within the cerebellar
cortex and with the DCN cells determines which of
these functions are associated with each other and
in which patterns these functions will influence the
neuronal networks of the extracerebellar structures from
which the functions originate (Bengtsson & Jörntell,
2014).
Although the description above is focused on somatic
motor control, and the specific support it has from
the spinocerebellar systems, similar circuitry constructs
for tapping off equivalent information also seem to be
present for ocular motor control systems (Porrill et al.
2004). It seems likely that such ‘recurrent’ circuitry
architecture exists also in cerebro-cerebellar systems of
the cerebellar hemispheres and the dentate nucleus (Kelly
& Strick, 2003; Bostan et al. 2013) where they could
be used for linking mental representations into learnt
‘spatio’-temporal patterns of neural activation. Such
mental representations could, for example, be internal
models of the relationship between the self and the
18 H. Jörntell
external world (Kawato et al. 2003; Ito, 2008), which
would be useful for motor planning. Conceivably, this
could form a substrate for linking thought processes and
mental associations to each other, although there is a long
way to go before we have a chance to understand the
spatiotemporal structure of the neural representation of
a thought. In this context, recent evidence indicating that
the dentate nucleus also projects, via the thalamus, to the
basal ganglia (Bostan et al. 2013; Chen et al. 2014), is also
likely to play an important role although that role is at
present unclear.
Climbing fibres regulate overall neuronal activity
and synaptic plasticity
In relation to the description of the circuitry structure
of the SCT/SRCT mossy fibre systems, it is interesting
to first note that the spinal contribution to the input
to the various parts of the inferior olive originates from
the same spinal circuitry components (Fig. 3). In fact,
it is even conceivable that they originate from the same
spinal neurons. Hence, for the parts of the cerebellum
concerned with somatic movement control, the mossy
fibre input and the input to the inferior olive originate
from functionally similar sources of information (Figs 2B
and 3), which are expected to be extensively engaged by any
type of somatic movement (Prut & Fetz, 1999). But what
does the climbing fibre system do for the function of the
cerebellum?
The climbing fibre synapse on the Purkinje cell had
already been identified as a uniquely powerful synapse of
the central nervous system 50 years ago (Eccles et al. 1967).
It was assumed that the activation of such a powerful
synapse was a teaching or an error signal informing the
Purkinje cells when they needed to re-learn their responses
to other (parallel fibre) input occurring at the same time
(Marr, 1969; Albus, 1971). Activation of the climbing
fibre synapse was originally thought to lead to long-term
potentiation (LTP) of the simultaneously activated parallel
fibre synapses, but it was soon discovered that it instead
was long-term depression (LTD) that was induced (Ito
et al. 1982; Ito, 1984). Nevertheless, the overall strong
agreement between the theoretical considerations and the
novel experimental data led to this form of cerebellar LTD
being considered synonymous with cerebellar learning
since then. Therefore, it has had profound influences on
our concepts of cerebellar function.
Cerebellar LTD is a powerful phenomenon, easily
demonstrable in experimental preparations using
localized activation of parallel fibres or local chemical
activation of AMPA receptors (Ito et al. 1982; Launey
et al. 2004). Indeed, in the adult state, most parallel fibre
synapses are silent, i.e. they have close to zero synaptic
efficacy (Ekerot & Jörntell, 2001; Isope & Barbour, 2002;
Jörntell & Ekerot, 2002, 2003). However, in the long
J Physiol 595.1
run, any system using synaptic plasticity as the learning
mechanism needs to have the means to change synaptic
weights in both directions. By gradually modifying the
synaptic weights, the connectivity of the system changes
and the response in a given context can be gradually
improved (Spanne & Jörntell, 2015). In this process,
however, the synapses that were initially given a low weight
may at a later stage of more mature synaptic weight
distributions gradually become useful to the system again.
Therefore, it is necessary that the parallel fibre synapses on
Cerebellar A B C1 C2 C3 D1-DN
cortex
Inferior olive cMAO cDAO rDAO rMAO PO
? ? Cun
Brainstem
(prim. aff.)
DF
DLF
LF
Spinal cord Motor
signals
VF
Figure 3. The spino-olivocerebellar pathways for activation
of climbing fibres
The connections from spino-olivocerebellar pathways (SOCPs) to the
climbing fibres of the cerebellar cortex, via specific parts of the
inferior olive, are illustrated. VF, ventral funiculus (for the VF-SOCP);
LF, lateral funiculus; DLF, dorsolateral funiculus; DF, dorsal funiculus;
Cun, main cuneate nucleus; cMAO, caudal medial accessory olive;
cDAO, caudal dorsal accessory olive; rMAO, rostral medial accessory
olive; rDAO, rostral dorsal accessory olive; PO, principal olive.
Connectivity based on Oscarsson (1969), Armstrong et al. (1973),
Oscarsson & Sjölund (1977), Ekerot & Larson (1979), Andersson &
Eriksson (1981), Voogd & Glickstein (1998), Shrestha et al. (2012),
Flavell et al. (2014) and Koutsikou et al. (2015). Cerebellar cortical
zones are indicated as in Fig. 1, with DN indicating that there may be
multiple D zones not yet identified in the hemispheres of higher
animals such as primates, which have different specific
functions/targets in regulating the neocortex (Bostan et al. 2013).
Note that, similar to the brainstem mossy fibre pathways in Fig. 2B,
the inferior olive also receives direct motor command signals
(McCurdy et al. 1992), which are omitted for clarity. Question marks
indicate that some of the SOCPs pass through synaptic relays in the
brainstem that are yet to be identified.

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J Physiol 595.1
the Purkinje cell can also be potentiated. Indeed, several
experimental studies indicate the presence of postsynaptic
LTP in this synapse (Jörntell & Ekerot, 2002; Lev-Ram et al.
2002; Coesmans et al. 2004), and that the requirements
of this process are essentially a mirror image of the
requirements for LTD: low as opposed to high calcium, no
climbing fibre activation vs. the presence of simultaneous
climbing fibre activation, phosphatase inhibitor activity
as opposed to phosphatase activity (Jörntell & Hansel,
2006).
As both LTD and LTP of the parallel fibre synapses
on Purkinje cells can participate in shaping the synaptic
weight distribution, i.e. in shaping the connectivity of
the network, an important question is what is the
synaptic weight distribution among these synapses in early
development, before major learning events have started
taking place? At least as compared to rats as early as
postnatal day 17–21, the synaptic weight distribution in
the adult state is more skewed in that there are a few
synapses with much higher weights as well as a clearer
tendency for the majority of the parallel fibre synapses to
have a very low weight (Valera et al. 2012). This would
suggest that parallel fibre synapses from the beginning are
given low, but non-zero, weights and that the effect of
learning is to enhance a few and depress a majority of the
synapses.
In addition to inducing LTD of active parallel fibre
synapses on Purkinje cells, climbing fibre inputs also
exist to MLIs (Jörntell & Ekerot, 2002, 2003; Szapiro &
Barbour, 2007) where they induce LTP of active parallel
fibre synapses (Jörntell & Ekerot, 2002, 2003; Rancillac &
Crepel, 2004; Jörntell & Ekerot, 2011), i.e. the opposite
effect as compared to the parallel fibre synapses on
Purkinje cells. Parallel fibre input without climbing fibre
input leads to LTD of the parallel fibre input to the
interneurons (Jörntell & Ekerot, 2002, 2003; Rancillac &
Crepel, 2004; Jörntell & Ekerot, 2011). At least partly as a
consequence of this anti-parallelism in the parallel fibre
plasticity mechanisms, the temporal firing modulation
of Purkinje cells and their afferent interneurons can be
mirror images of each other in cyclic motions (Jörntell &
Ekerot, 2002; Barmack & Yakhnitsa, 2008). Indeed, when
the pattern of firing of the climbing fibre input changes
due to a re-routing of the ingrowth of climbing fibres to the
cerebellar cortex, the patterns of firing modulation during
such cyclic motions change accordingly in the Purkinje
cells and interneurons but remain mirror images of each
other (Badura et al. 2013).
Climbing fibres may hence have a strong governing
role for the shaping of the overall firing modulation
in relation to cyclic motions in Purkinje cells, which
can be explained by the parallel fibre synaptic plasticity
(Jörntell & Hansel, 2006) and the similarity of the
information that drives the mossy fibres and the climbing
fibres (Figs 2B and 3). However, as described above, the

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Cerebellar physiology 19
discharge rate of climbing fibres, their apparent active
suppression during movement (Horn et al. 2004), as well
as the wide temporal window for inducing LTD around
a climbing fibre discharge (Safo & Regehr, 2008; Jirenhed
et al. 2013), suggest that climbing fibre-governed plasticity
is insufficient to generate connectivity patterns with the
high degree of specificity that would be needed for the
integration of information and the coordination of more
complex, high-dimensional systems. In contrast, parallel
fibre LTP in Purkinje cells and interneurons could be
sufficiently temporally specific to solve this problem even
though that remains to be shown.
The cerebellar microcircuitry: associative
and activity-balancing subsystems
In a scenario where spike times are non-deterministic
(Spanne et al. 2014b) and sparse coding is not a
main organizational principle, but the cerebellum is
instead considered responsible for forming and linking
models in a regressor-like fashion with a high capacity
for generalization (Spanne & Jörntell, 2015), the main
function of the cerebellar cortex becomes that of a giga-
ntic associative element. In this associative machine,
mossy fibre input/information can contribute to driving
or suppressing the Purkinje cell spike output depending
on whether the information is mediated directly via the
parallel fibre or indirectly via the parallel fibre–inhibitory
interneuron. The central point of the cerebellar cortex
then becomes to learn which parts of the incoming mossy
fibre information should be associated with each other,
and with what relative weights (where even negative
weights are hence allowed), in relation to the functional
contribution of the Purkinje cell (Fig. 4). The inhibitory
effect of the Purkinje cell is exerted on the cerebellar
nuclear neuron, which in itself can be excited by direct
mossy fibre inputs. Hence, if the Purkinje cell is inhibited
by inhibitory interneurons during a particular phase of
a movement, the cerebellum can in principle generate
net excitation of downstream motoneurons, even though
that net excitation is dependent on activity in the spino-
cerebellar neurons that is driven by motor centres. As
will be argued below, depending on the complexity of
the system controlled, a straightforward function for
the cerebellum to find and store useful associations
between sensorimotor functions within a very rich set of
information is sufficient to achieve complex functionality
at the same time as it may still be possible to survive
without its contribution, i.e. at least in humans in modern
society where the full range of the behavioural repertoire
made possible with an intact cerebellum may not be
necessary for survival.
For the control of one-dimensional systems, like the
vestibulo-ocular reflex where individual microzones may
control eye movements in one dimension (one muscle)
20 H. Jörntell J Physiol 595.1

A Cerebellum - ‘function’ circuitry and activity balancing circuitry with input from the vestibular organ as a main driver
IO
of the motor output cells in the vestibular nuclei (Ito,
1984; Jörntell & Hansel, 2006), the function of the
cerebellum becomes that of a relatively simple gain control.
ii
GoC i Firing
The mossy fibre inputs that are relevant for the gain
MLI
Firing PF synapse of the movement dimension controlled are specifically
grc potentiated or depressed in order for the reflex to work
mf PC
appropriately (i.e. controlling the gain of the reflex
pathway so that the retinal image does not slip as the
head moves).
DCN For multi-dimensional systems, like whole-body or
whole-limb control, the range of possibilities becomes
much wider. A key element is the interaction between
the muscle output and the biomechanics of the body.
B Cerebellum ‘function’ circuitry The biomechanics is the ‘filter’ that determines in which
spatiotemporal pattern the sensors become activated for
Plasticity/learning:
changing the matrix
a given muscle output (Spanne & Jörntell, 2013). The
MLI patterns of sensor activation represent the readout of the
effect of the motor command on the body. The pool of
PC spinal interneurons, which have a key position in somatic
Mossy fibres ?
Monitoring sensorimotor population inf. motor control and are activated by a combination of
motor command signals and the sensor feedback, carries
DCN this information (Fig. 2B). At the same time as this
information is used to activate the α-motoneurons, parts
Effect on motor output population code
of it are also forwarded to the cerebellum through the
axon branches of these spinal interneurons via the SCTs
and the SRCTs. However, the spinocerebellar information
C Cerebellum ‘effective function’ circuitry is decomposable into smaller functional units, i.e. the
information carried by the individual spinal interneurons.
PC (+MLI) Spinal interneurons are by means of their branching
patterns natural synergy controllers, i.e. they individually
Mossy fibres control multiple muscles (Jankowska, 1992; Santello et al.
Monitoring sensorimotor
population inf. DCN 2013). What could be achieved via the cerebellum is that
different sets of synergy controllers can be linked to each
other to form more well-composed synergies (Bengtsson &
Effect on motor output population code
Jörntell, 2014), or chains of synergies linked to each other
in a particular temporal sequence. Thereby, smoother,
faster, more complex and probably also more precise
movements can be achieved than what would have been
Figure 4. Proposed division into functional and activity possible to achieve without the cerebellum.
balancing circuitry in the cerebellum
A, cerebellar circuitry with the major cellular components, including
the feedback control of the inferior olive (IO) from the deep
cerebellar nucleus (DCN). Mossy fibres (mf) provide the main driving weights in the matrix of the mossy fibre-to-Purkinje cell connections.
input of the circuitry and synapse with the granule cells (grc) and the Plasticity at other types of synapses contributes primarily to the
DCN cells. The grcs are under inhibitory control from the Golgi cells activity balancing of the circuitry. C, assuming that the main function
(Goc). grc information is forwarded to the molecular layer of MLIs is to make it possible to invert the polarity of the mf–grc
interneurons (MLI) and the Purkinje cells (PC), where the latter input, the MLIs can be eliminated from the ‘effective function’
provide the output of the cortex in the format of inhibitory input to circuitry if one assumes that the mf–grc synaptic input can be
the DCN cells. The DCN cells in turn provide the output of the assigned both positive and negative weights in learning processes.
cerebellum, the route by which effects on various motor command The circuitry hence becomes much simplified, but can still achieve
structures are exerted. The IO provides the cerebellar cortex with complex functions due to the fact that each PC receives input from a
climbing fibres, which have a very powerful synapse on the PCs, but massive population of mfs with a wide spectrum of information and
also contact MLIs and Gocs. B, in the proposed interpretation, the patterns of temporal activation (matrix to the left). Also the output
functional components of the circuitry can be limited to the MLIs, of the cerebellum should likewise be considered as a massive
PCs and DCN output neurons, where the mossy fibre input (via population of outputs (matrix to the right), where each individual
granule cells in the case of the MLIs and the PCs) is the main plastic DCN neuron only carries a fragment of the information necessary for
component that can mediate functional change by altering the the control of the motor output structures.


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J Physiol 595.1
The conclusion from this reasoning is that for the
aspects of motor function that we normally associate with
the cerebellum, it is probably sufficient to assume that
its role is to link the appropriate combinations of mossy
fibre inputs with each other on a Purkinje cell-by-Purkinje
cell basis. The specification of what mossy fibre inputs are
relevant for a particular Purkinje cell should depend on its
function, i.e. its contribution to ongoing movements via
the DCN cells. This function is determined by the motor
output structures that the DCN cell targets (Fig. 1), and
what particular spinal interneurons it influences via the
population of neurons contacted in those output targets.
Here it is important to realize that a Purkinje cell is never
activated alone. All motor output can be expected to result
in a very large number of Purkinje cells, DCN cells and
spinal interneurons being activated together alongside all
of the motor command structures of the brainstem and
motor cortex. Therefore, the effect that the output of any
single Purkinje cell will have depends on in which context,
i.e. sensorimotor state, the output occurs. An essential
contribution from the mossy fibre systems therefore will
be to signal the state. As a very high number of states
are possible (Spanne & Jörntell, 2015), a main task of the
Purkinje cell will be to keep track of which state applies
at the moment and to learn which types of mossy fibre
signals it should associate with that state. At the same
time, the synaptic weight of a mossy–parallel fibre synapse
can take only one value, which applies across all states,
and if a Purkinje cell is to be able to contribute to motor
control across all states it needs to find a set of synaptic
weight distributions for all mossy–parallel fibre inputs
that applies across all states. This is a very demanding
task that requires an enormous memory storage capacity,
which may explain why the Purkinje cell dendritic tree has
assumed such enormous proportions.
A major issue is how the learning of such multiple
states can be achieved at the cellular level. First, it is
important that the mossy fibre–parallel fibre system does
not follow sparse coding principles. This is because the
ability to make learned circuitry structures generalizable,
i.e. to be useful across multiple states or contexts, is most
effectively provided by a system with a more dense coding
strategy. In the case of the cerebellum, this would translate
to many or all granule cells participating in all contexts,
although each individual granule cell does so with a fine
graded signal that depends on the state and where also
zero activity counts (Spanne & Jörntell, 2015). Second, it
is known that the parallel fibre synaptic inputs to both
Purkinje cells and their afferent molecular layer inter-
neurons are bi-directionally plastic, i.e. they can both
be potentiated or depressed (Jörntell & Ekerot, 2002;
Rancillac & Crepel, 2004; Jörntell & Hansel, 2006; Dean
et al. 2010; Jörntell et al. 2010). In this context, climbing
fibres are expected to play an important role, since their
activation is a signal for the parallel fibre synapses on the

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Cerebellar physiology 21
Purkinje cells to become depressed (LTD) and those on
the molecular layer interneurons to become potentiated
(LTP). However, the activity of the climbing fibre system
is typically depressed during active movement (Horn et al.
2004) and the time of activation of individual climbing
fibre discharges is widely stochastic (Bengtsson & Jörntell,
2009a) and does not seem to have the temporal precision in
relation to movement execution that would be required of
a system carrying the main responsibility for the formation
of the high precision synaptic weight distributions that
could support the performance of that movement at any
level of detail. However, it is essential with a powerful
system for down-regulating the efficacy of synaptic weights
in the cerebellum: if all granule cells, i.e. all mossy
fibre–parallel fibres, participate in the signalling of all
states, the complexity of the learning required becomes
very high unless a majority of the parallel fibre synapses
are kept silent, i.e. given near-zero synaptic weight (Spanne
& Jörntell, 2015). The climbing fibre induced LTD of
parallel fibre synaptic input to the Purkinje cells fulfils this
criterion: it is a low-threshold, powerful form of synaptic
plasticity (Launey et al. 2004), which is induced across a
wide time-window relative to the occurrence of climbing
fibre input (Safo & Regehr, 2008; Jirenhed et al. 2013)
and appears to leave most parallel fibre synapses silent
(Ekerot & Jörntell, 2001; Isope & Barbour, 2002; Valera
et al. 2012). Finally, although the context that applies at
any given moment is likely to be primarily signalled by
the mossy fibre systems, it is also possible that the tonic
Golgi cell inhibition of granule cells can participate in this
signalling, by regulating the excitability of the granule cells
according to state (Spanne & Jörntell, 2013).
Rationale for the need of an activity balancing system in
the cerebellum. Both Purkinje cells and their target DCN
neurons are firing perpetually. During behaviour, their
firing can be deeply modulated, but never ceases for any
longer duration of time. Since the cerebellum has a pivotal
role in motor output, by direct connections to all of the
major motor output structures, it becomes important to
make sure that this output does not transgress outside
an overall range of activity over time. As a practical
example, this is likely to be useful to avoid overexcitation of
muscles, or to avoid muscles and α-motoneurons having
an excitability too low to become instantly activated
when motor command signals arrive. Indeed, a clinical
manifestation of stroke lesions in the cerebellum appears
to be an altered excitability in peripheral motor axons
(Huynh et al. 2014).
Hence, many aspects of the cerebellar neuronal
circuitry, in particular the Golgi cells and their inhibition
of granule cells, but also the low rate, spontaneous
activation of climbing fibre synapses on Purkinje cells
could serve as a regulatory system that keeps the over-
all activity of the tonic output of the cerebellar cortex and
22 H. Jörntell
nuclei within operative range (Jörntell, 2016). The main
arguments for this view is that unlike very young animals
(Brickley et al. 1996; Duguid et al. 2015), in the adult
state the Golgi cell to granule cell inhibition appears to
be almost entirely tonic with little or no fast IPSP effects
(Brickley et al. 1996; Jörntell & Ekerot, 2006; Bengtsson
et al. 2013). Thereby, they cannot substantially contribute
to fast cortical processing, but they can regulate granule
cell excitability from one context to another (Spanne &
Jörntell, 2013). Golgi cells are by themselves regulated by
an inhibitory input from Lugaro cells, which are in turn
regulated by serotonin (Dieudonne & Dumoulin, 2000).
For the climbing fibre synapses on Purkinje cells, it is
clear that apart from contributing to the LTD of parallel
fibre synapses, and thereby reducing the overall amount
of excitatory synaptic input, they also directly regulate
Purkinje cell simple spike output over longer time scales
(Bengtsson et al. 2004; Cerminara & Rawson, 2004). Such
regulation could, for example, involve the expression of
metabotropic glutamate channels at the sites of the parallel
fibre synapses activated in conjunction with the climbing
fibre synapse (Johansson et al. 2015). Because of the feed-
back via the inhibitory control of the inferior olive from
specific cells in the cerebellar nucleus (Svensson et al. 2006;
Chaumont et al. 2013), the output of the Purkinje cells
can be used to control their own overall level of firing.
Perturbing this feedback control system leads to severe
problems. Inactivation of the inferior olive, which can be
expected to result in a dramatic increase in the firing of
the Purkinje cells being contacted by the corresponding
climbing fibres (Bengtsson et al. 2004; Cerminara &
Rawson, 2004), leads to severe loss of muscle tone control
and motor deficits (Horn et al. 2010, 2013), with the
specific deficit being dependent on which particular part of
the inferior olive (i.e. which sagittal zones that are affected,
Fig. 1) is inactivated.
Cerebellar coding and granule cell function
The circuitry structure portrayed above provides limited
opportunity to perform advanced operations to trans-
form the information that the cerebellum receives from
the numerous mossy fibre pathways. In particular the
absence of dominant intrinsic recurrent connectivity
within the cerebellar cortex in principle excludes any other
possibility than that of a pure associative function of
this network. This arrangement arguably makes sense,
since the information that is provided at least by the
spinocerebellar systems (Jankowska et al. 2011b; Shrestha
et al. 2012; Spanne & Jörntell, 2013), and also the
cuneocerebellar system (Jörntell et al. 2014), represents
relatively precise and specific information that it may not
be wise to transform to a substantial extent. The fact
that the Purkinje cell firing pattern in some cerebellar
areas correlates with predictions of limb kinematics
J Physiol 595.1
across multiple behavioural contexts (Pasalar et al. 2006)
could, for example, be explained by these Purkinje cells
combining specific information from the SCT/SRCTs. The
huge potential for associative function in the cerebellar
cortex, and in particular the Purkinje cells, was also
one of the first potential functions recognized by early
investigators (Eccles et al. 1967; Marr, 1969; Albus, 1971).
However, in addition, the very high numbers of granule
cells were historically assumed to imply that some major
transformation of the mossy fibre information was carried
out at this level. In particular, Marr (1969) proposed that
a random combination of mossy fibre inputs occurred at
the level of the granule cells. Given that each granule cell
receives only in the order of four mossy fibre synaptic
inputs, the chances that each granule cell could be
given a unique condition of activation would be high in
this scenario. Further diversification of the granule cell
signalling was predicted to be achieved by the Golgi cell
inhibition of the granule cells. The idea of the granule
cell layer as an expansion recoding unit, i.e. where mossy
fibre information from different sources is combined
to generate a new and richer set of information, fitted
the likewise early idea of the output Purkinje cell as a
‘perceptron’ (Albus, 1971). As a perceptron is an element
with a binary activation function, each Purkinje cell was
expected to be activated by a unique combination of
granule cell input patterns. Because of the uniqueness of
the input, each Purkinje cell was expected to be activated
primarily during a particular phase of the movement and
thereby contribute to motor control. For discriminative
functions such as this, where the cerebellum is assumed
to work as a classifier of contexts and use that as a means
to control motor programme activation, it is important to
have as diverse a set of inputs as possible to the associative
layer.
Due to the fact that granule cells for many decades
remained impossible to record from, these ideas became
highly influential. However, over the last decade granule
cell recordings in the cerebellum in vivo have emerged
(Chadderton et al. 2004; Jörntell & Ekerot, 2006; Arenz
et al. 2008; Bengtsson & Jörntell, 2009b) and major
revelations have followed. Clearly, the initial ideas of each
granule cell being activated by a unique event and then
only firing in a sparse coding mode has proven incorrect
(Jörntell & Ekerot, 2006; Ozden et al. 2012; Powell et al.
2015; Spanne & Jörntell, 2015). Furthermore, a binary
activation function of a perceptron in the Purkinje cells
is in principle impossible to defend given what we now
know of the firing patterns in which the Purkinje cells are
normally activated (Pasalar et al. 2006; Hewitt et al. 2011).
However, the idea of each granule cell being activated by a
unique combination of mossy fibre inputs still lingers.
It has recently been supported in a couple of studies,
which report that different mossy fibre systems converge
in a single granule cell (Huang et al. 2013; Chabrol

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et al. 2015). Against these stand directly contradicting
observations on the absence of integration of different
types of information in the granule cells (Jörntell & Ekerot,
2006; Bengtsson & Jörntell, 2009b), and a fundamentally
different type of observation, i.e. that input from single
mossy fibre pathways are sufficient to activate Purkinje
cells (and, naturally, granule cells) (Ekerot & Jörntell,
2001; Geborek et al. 2013b, 2014). There are two possible
ways to reconcile these observations. One is to assume
that the convergence between different types of mossy
fibre information at the granule cell layer results in too
much of a loss of information in systems devoted to the
control of multi-dimensional systems (Jörntell & Ekerot,
2006; Bengtsson & Jörntell, 2009b; Geborek et al. 2013b,
2014), whereas in the more low-dimensional system, such
as in eye movement control (Chabrol et al. 2015), this
loss can be afforded and could even lead to advantages.
The other explanation is that the specific structures that
have been labelled for anterograde mossy fibre tracing in
the anatomical studies (Huang et al. 2013; Chabrol et al.
2015) are not functionally different, i.e. they convey in
principle equivalent information. In the study of Huang
et al. (2013), the convergence of the basilar pontine
nucleus and the external cuneate nucleus mossy fibres on
granule cells may not necessarily mean that they represent
functionally different information as the external cuneate
nucleus projects to the pontine nuclei, and both structures
receive cerebral input (Fig. 2B). Likewise, Chabrol et al.
(2015) studied inputs from the medial vestibular nucleus,
the vestibular ganglion and the prepositus hypoglossi
nucleus (PrH), where the latter was described as being
a system mediating visual inputs. However, similar to the
former two systems, PrH is also directly involved in the
control of eye movements and hence all three inputs may
correspond to motor commands (McFarland & Fuchs,
1992).
Assuming that the main activation of the granule cells
comes from mossy fibres containing the same type of
information from SCTs (Fig. 2B), a simulation predicting
how granule cells may respond under locomotion (Spanne
et al. 2014a) has striking qualitative similarities with actual
granule cell responses during this condition in awake mice
(Powell et al. 2015). Hence, current understanding of the
granule cells is sufficient to approximately predict how
they will be activated under behaviour, given that a general
idea of how the afferent spinocerebellar mossy fibres are
activated is available.
Concluding statement
For the functional description at the neuronal circuitry
level, the present-day understanding of the cerebellum is
arguably unsurpassed in the mammalian brain. Due to
the library of knowledge of cellular and synaptic physio-
logical properties, as well as of the overall rules of plasticity

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Cerebellar physiology 23
that shape the patterns of synaptic connectivity, it is today
theoretically possible to compute how the circuitry would
respond and adapt to virtually any spatiotemporal pattern
of mossy fibre information. However, this is also where
today’s challenge lies: the cerebellum receives information
from a vast set of mossy fibre systems and the nature
and spatiotemporal format of that information in relation
to different types of behaviour need to be known in
order to tell exactly what the cerebellum does in a given
situation and in a given region. This issue is related to
the larger issue of how information in the brain arises in
the first place and how it is represented in the brain once
generated.
Hence, for future advances of the field of cerebellar
physiology a better characterization of the information
forwarded by the different mossy fibre systems is urgent.
The realization that most mossy fibre systems can be
expected to be activated across many motor contexts,
and that cerebellar learning therefore requires synaptic
weights to become applicable across these contexts, is also
a factor that needs to be taken better into account for any
model of cerebellar circuitry function. The division of the
cerebellar circuitry into activity balancing and associative
components that is proposed here also awaits further
experimental testing. Finally, an exciting future prospect
is that the emerging understanding of how the sensori-
motor mossy fibre information is formatted in order to
be processed by the cerebellar circuitry will also lead to
insights regarding the format of information from mental
processes that is processed in other subdivisions of the
cerebellum using a similar generic circuitry structure.
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Additional information
Competing interests
None declared.
Funding
The author is supported by Vetenskapsrådet (Swedish Research
Council; K2014-63X-14780-12-3).
Acknowledgements
The author wishes to thank Professor Gerald E. Loeb for valuable
suggestions and comments.