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22 Purkinje Cells
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Stellate Cells
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SiqiongJuneLiu andChristopheJ.Dubois
23
Abstract
Stellate cells are inhibitory GABAergic interneurons
located in the molecular layer of the cerebellar cortex.
Stellate cells receive excitatory glutamatergic inputs from
parallel bers (PF) and climbing bers, as well as inhibitory GABAergic input from other stellate cells and
Purkinje cell axon collaterals (Witter et al. Neuron
91:312–319, 2016). These inhibitory interneurons suppress the activity of Purkinje cells through feed-forward
inhibition. A variety of mechanisms regulate GABA
release at inhibitory synapses in the cerebellar cortex and
consequently alter cerebellum-dependent motor and nonmotor functions.
Keywords
Inhibitory interneurons · Stellate cells · Synaptic
plasticity · AMPA receptors · GABA release · Behavior
23.1 Introduction
The cerebellum plays a central role in motor control and
motor learning. Research using a variety of genetic
approaches to modify inhibitory transmission has revealed
that cerebellar interneurons are critical in both motor coordination and motor learning. In vivo studies show that selectively increasing GABAergic signaling onto Purkinje cells
triggers decits inlocomotor behaviors (Wulff etal. 2007;
Jelitai etal. 2016) and that enhancing GABA release from
S. J. Liu (*)
Department of Cell Biology and Anatomy, LSU Health Sciences
Center, New Orleans, Louisiana, USA
Southeast Louisiana VA Healthcare System, New Orleans,
Louisiana, USA
e-mail: sliu@lsuhsc.edu
C. J. Dubois
Univ. Bordeaux, CNRS, RMSB, Bordeaux, France
stellate cells causes type 1 episodic ataxia (Herson et al.
2003). Genetic deletion of GABA receptors on Purkinje cells
impairs the consolidation of vestibulocerebellar motor learning (Wulff etal. 2009). Cerebellar activity is also required
for associative fear conditioning and eye-blink conditioning.
These two forms of associative learning both enhance interneuron activity and GABA release, a change that is reversed
by extinction training (Scelfo etal. 2008; Dubois etal. 2020;
Dubois and Liu 2021). Given the importance of inhibitory
transmission in cerebellar function, GABA release at inhibitory synapses in the cerebellum is closely regulated.
23.2 Stellate Cells andSynaptic
Transmission
23.2.1 Excitatory Synaptic Transmission
Stellate cells are electrically compact and can be activated by
a single excitatory input, triggering GABA release onto
Purkinje cells at stellate cell to Purkinje cell synapses.
Because PFs also innervate Purkinje cells, feed-forward
inhibition via stellate cells gives rise to a delayed inhibition
and thereby restricts the glutamatergic excitation of Purkinje
cells to the onset of excitatory input. Excitatory transmission
at the PF to stellate cell synapse is mediated by postsynaptic
AMPA receptors. Receptors at proximal dendrites lack
GluA2 subunits and are permeable to Ca2+, whereas AMPA
receptors that contain GluA2 subunits are present at distal
dendrites and are not permeable to Ca2+ (Savtchouk et al.
2016). Excitatory postsynaptic currents (EPSCs) via GluA2-
lacking receptors display rapid kinetics and an increased current amplitude when activated by two consecutive stimuli,
allowing stellate cells to respond to high-frequency excitatory inputs, such as that occurs during sensory stimulation
(Chadderton et al. 2004; Chen et al. 2017). Ca2+ entry via
AMPA receptors triggers the release of endocannabinoids
from stellate cells, and these retrograde transmitters reduce
glutamate release from PFs (Soler-Llavina and Sabatini
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
D. L. Gruol et al. (eds.), Essentials of Cerebellum and Cerebellar Disorders, https://doi.org/10.1007/978-3-031-15070-8_23
163
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S. J. Liu and C. J. Dubois
2006). Consequently, this lowers the excitatory drive for
feed-forward inhibition in the cerebellar circuit.
NMDA-type glutamate receptors are present at extrasynaptic sites and are activated by glutamate spillover during
trains of presynaptic parallel ber or climbing ber stimulation (Carter and Regehr 2000; Szapiro and Barbour 2007).
The NMDAR response requires the presence of neuroligins,
which are postsynaptic cell-adhesion molecules (Zhang and
Südhof 2016). These NMDARs contain GluN2B and 2D
subunits, and exhibit slow kinetics (Dubois et al. 2016).
Therefore, stellate cells receive glutamatergic inputs from
parallel bers and can also be activated by “spillover” of glutamate released from climbing bers (Arlt and Häusser
2020). Thus, stellate cells are a site of modulation during
associative learning or during the co-activation of parallel
and climbing bers.
23.2.2 Regulation ofPostsynaptic Glutamate
Receptors
Synaptic AMPA receptors in stellate cells undergo dynamic
changes in response to presynaptic activity. Repetitive stimulation of PFs triggers a long-lasting increase in synaptic
GluA2 content, which replaces GluA2-lacking AMPA receptors in stellate cells (Liu and Cull-Candy 2000). This not
only reduces the amplitude and prolongs the decay time of
EPSCs but also lowers the level of Ca2+-permeability of
AMPA receptors, producing a qualitative change in synaptic
transmission. The switch is triggered by activation of synaptic AMPA or extrasynaptic NMDA receptors, and requires a
Ca2+-rise that activates PKC, leading to a PICK-dependent
insertion of GluA2-containing receptors (Liu and CullCandy 2000; Sun and Liu 2007). Activation of metabotropic
glutamate receptors (mGluRs) can also induce a switch in
AMPA receptor subtypes via a mechanism that requires
protein synthesis (Kelly etal. 2009). The switch in synaptic
AMPA receptor phenotype reduces the ability of sensory
stimulation to evoke multiple action potentials in stellate
cells and thereby weakens the feed-forward inhibition.
Stimulation of climbing bers also evokes excitatory synaptic response in stellate cells. Co-stimulation of these two
excitatory inputs invivo induces a lasting increase in excitatory postsynaptic potentials (EPSPs) at the PF-stellate cell
synapse, which is reversed by stimulation of PFs alone
(Jörntell and Ekerot 2003). An AMPA receptor subtype
switch in stellate cells may mediate this invivo.
Acute stress can enhance gene transcription of GluA2in
stellate cells (Liu etal. 2010). Release of norepinephrine in
the cerebellum activates β-adrenergic receptors and elevates
cAMP levels. This increases Ca2+ entry during action potentials, activates ERK pathways, and promotes GluA2 transcription in stellate cells. Consequently, the elevated GluA2
expression prolongs the synaptic current duration (i.e.,
EPSC) and enhances the ability of each synaptic input to
evoke an action potential and thus the feed-forward inhibition (Savtchouk and Liu 2011). Therefore, acute stress can
induce a lasting change in activity and computation within
cerebellar circuitry.
23.2.3 Modulation ofInhibitory Synaptic
Transmission by NMDA Receptors
Interneurons innervate each other to form inhibitory networks and provide the inhibitory inputs to Purkinje cells.
Enhanced GABA release by the inhibitory interneurons is
thought to promote synchronous activity of the interneuron
network and suppress Purkinje cell activity. Glutamate
released from PFs and Purkinje cell dendrites enhances the
release of GABA from stellate cells (Duguid and Smart
2004; Liu and Lachamp 2006), altering the balance between
excitatory and inhibitory transmission. A train of PF stimulation triggers glutamate spillover which activates NMDA
receptors located at the presynaptic terminals of stellate
cells, inducing a lasting increase in GABA release from
these interneurons via a mechanism that requires PKA and
an active zone protein, RIM1α (Lachamp etal. 2009; Dubois
etal. 2016). This alters the pattern and reduces the frequency
of action potential ring in synaptically connected stellate
cells. While repetitive PF activation triggers a lasting increase
in GABA release in naïve mice, this stimulation paradigm
induces a sustained decrease in GABA release after fear conditioning. NMDA receptors that contain GluN2D subunits
drive this form of presynaptic long-term depression (Dubois
and Liu 2021). Thus, learning can alter the direction of
NMDA receptor-dependent synaptic plasticity at cerebellar
inhibitory synapses, inducing a form of metaplasticity of
GABA transmission. Activation of extrasynaptic NMDA
receptors also strengthens GABAA receptor-mediated transmission via a NOS-cGMP-PKC pathway, and this requires a
GABA receptor-associated protein (Larson et al. 2020).
Therefore, NMDA receptors regulate both GABA release
from presynaptic terminals and postsynaptic GABAA receptors, controlling inhibitory transmission from stellate to
Purkinje cells and between stellate cells, changing the balance between excitatory and inhibitory transmission in the
cerebellum.
23.2.4 Presynaptic Regulation by
Neuromodulators
Endocannabinoids are critically involved in learning and
extinction, and dysregulation of endocannabinoid metabolism leads to cerebellar ataxia in PHARC disease
(Fiskerstrand etal. 2010). In the cerebellar cortex, depolarization of Purkinje cells and interneurons triggers the release
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of endocannabinoids which activate G-protein coupled CB1
receptors at the presynaptic terminals of interneurons
(Yoshida et al. 2002; Beierlein and Regehr 2006; Dubois
etal. 2020). This decreases GABA release and reduces action
potential ring in stellate cells (Kreitzer et al. 2002). The
axons of interneurons extend over several hundred micrometers in the parasagittal plane and inhibit neighboring
Purkinje cells, producing lateral inhibition. Thus, inhibition
of interneuron ring can lead to lateral excitation in the cerebellar cortex.
Associative fear conditioning induces a lasting increase in
GABA release (Scelfo etal. 2008; Dubois etal. 2020; Dubois
and Liu 2021). The potentiation of the inhibitory transmission results from a decrease in the degradation of 2-AG, the
major endocannabinoid in the cerebellar cortex. This leads to
a sustained decrease in the level of the endocannabinoid,
2-AG, and dis-inhibits (and therefore enhances) GABA
release (Dubois etal. 2020). This learning-induced decrease
in endocannabinoid signaling in the cerebellum is critical for
the formation of associative fear memory. Other neuromodulators, including noradrenaline (Llano and Gerschenfeld
1993) and neuropeptide Y (Dubois etal. 2012) also induce a
sustained increase in GABA release.
23.3 Gap Junctions
Interneurons are connected via gap junctions allowing current ow between neighboring cells. These electrical connections play a key role in the temporal synchronization of
neuronal activity (Mann-Metzer and Yarom 1999; Hoehne
etal. 2020). Each stellate cell is directly connected to one
neighboring interneuron in the sagittal plane (Alcami and
Marty 2013). Thus, changes in membrane potential can
spread among interneurons. The pattern of connections
(Rieubland etal. 2014) contributes to the spatial convergence
onto Purkinje cells where seven interneurons form functional
synapses onto a single Purkinje cell (Kim et al. 2014).
Therefore, electrical networks spatially and temporally coordinate interneuron activity and ultimately inuence the convergence of synaptic inhibition onto Purkinje cells, the only
output neurons in the cerebellar cortex. In conclusion, both
Fig. 23.1 Schematic drawing of GAP junctions and synaptic connections between two molecular layer interneurons and between interneurons
and Purkinje cells
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S. J. Liu and C. J. Dubois
chemical and electrical synapses are critical in shaping the
activity of Purkinje cells and controlling information processing in the cerebellum (Fig.23.1).
23.4 Intrinsic Excitability
Voltage-gated ion channels in stellate cells control action
potential waveform, enable spontaneous action potential ring, and inuence the neuronal response to synaptic inputs.
Action potentials in stellate cells are brief in duration and
this results from activation of large-conductance of Ca2+ activated K+ channels (Liu etal. 2010, 2011). A transient outward K+ current (IA) prolongs the latency of action potential
ring in response to depolarizing current injection, but activation of a transient inward Ca2+ current, IT, shortens its
latency (Molineux et al. 2005). These voltage-gated ion
channels determine the timing and pattern of action potential
ring in response to an excitatory postsynaptic potential at
parallel ber synapses and are involved in feed-forward inhibition onto Purkinje cells. Cerebellar stellate cells exhibit
spontaneous activity in the absence of synaptic input, which
is modulated by two channels that are activated at resting
potentials. The frequency of spontaneous action potentials is
elevated by a hyperpolarization-activated cation current, but
suppressed by a G protein-activated inward rectier K+ current (Kreitzer etal. 2002). Action potentials spread passively
from soma to dendrites and elevate dendritic Ca2+ levels.
Dendritic Ca2+ signals can evoke endocannabinoid production from these interneurons and suppress presynaptic neurotransmitter release (Myoga etal. 2009).
Several voltage-gated ion channels are present in the presynaptic terminals of cerebellar inhibitory interneurons. Of
these channels, inhibition of Kv1 potassium channels
enhances GABA release, whereas an Ih antagonist reduces
GABA secretion. Kv3 potassium channels located at presynaptic boutons (Rowan etal. 2016) promote action potential
repolarization and limit the Ca2+ rise in presynaptic terminals
(Tan and Llano 1999). Therefore, voltage-gated ion channels
at axon terminals of cerebellar interneurons play a central
role in regulating neurotransmitter release.
23.5 Stellate Cells inMotor andNon-motor
Behaviors
23.5.1 Motor Behaviors
Motor coordination is one of the primary functions of the
cerebellum and strongly depends on the pattern of action
potential ring in Purkinje cells (Walter etal. 2006; Alviña
and Khodakhah 2010). Inhibitory interneuron activity controls the spike pattern in Purkinje cells and is critically
involved in motor coordination. Selective enhancement of
inhibitory transmission reduces the regularity of action
potential ring in Purkinje cells and causes decits in motor
performance on a rotarod test (Wulff etal. 2007). Mutations
in the Kv1.1 potassium channel that enhances GABA release
from stellate cells also impair rotarod performance and cause
type 1 episodic ataxia (Browne et al. 1994; Herson et al.
2003). Several studies have used chemogenetic and optoge-
netic approaches to increase and suppress the activity of cerebellar inhibitory interneurons and determine their role in
motor movement. Suppression of interneuron activity
reduces lick rate and alters tongue movements (Gafeld and
Christie 2017), whereas stimulation of these neurons evokes
eyelid closure and orofacial movements (Heiney etal. 2014).
Therefore, the activity of cerebellar interneurons regulates
motor movement perhaps through their synchronized activity shown during motor behavior (Astorga etal. 2017) and by
controlling Purkinje cell action potential ring.
23.5.2 Motor Learning
Inhibitory transmission onto Purkinje cells is critical for the
vestibulo-ocular reex (VOR), a form of cerebellumdependent motor learning. Selective deletion of GABAA
receptors in Purkinje cells alters the temporal pattern of
action potential ring in Purkinje cells to become more regular. Mutant mice show impairment both in VOR phase reversal learning and in their ability to consolidate gain adaptations
(Wulff et al. 2009), demonstrating the importance of feedforward inhibition in motor learning.
23.5.3 Associative Learning
23.5.3.1 Classical Eye-Blink Conditioning
Cerebellar circuits play a central role in a well-characterized
associative learning process, classical eye-blink conditioning
(McCormick and Thompson 1984). Following repeated pairing, a conditioned stimulus (a tone or forelimb stimulation)
with an air puff to the eye, animals learnt to blink in response
to the conditioned stimulus alone. The conditioned response
is associated with acquisition of an increased ring frequency in inhibitory interneurons and an inhibitory response
in Purkinje cell activity to the conditioned stimulus and this
is reversed by extinction training (Hesslow and Ivarsson
1994; Jirenhed etal. 2007). Disruption of inhibitory trans-
mission by deletion of GABAA receptor subunits or the
potassium-chloride co-transporter KCC2 in Purkinje cells
impairs conditioned eyelid responses (ten Brinke etal. 2015).
Learning alters the inhibitory interneuron response to the
conditioned stimulus. Thus, inhibitory transmission is critical for the conditioned response.
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23.5.3.2 Associative Emotional Memory
Cerebellar outputs project to non-motor brain regions important for emotional regulation (Bostan etal. 2013) and clinical
studies show that the cerebellum is critical for cognitive and
affective behaviors (Schmahmann 2010). Associative fear
conditioning is an animal model for emotional learning and
memory and reversible inhibition of cerebellar activity after
fear conditioning impairs memory consolidation (Sacchetti
etal. 2002, 2004). This learning paradigm reduces endocannabinoid signaling and thereby induces a long-lasting
increase in interneuron activity and GABA release in vermal
lobules V/VI (Dubois etal. 2020). Chemogenetic activation
of Gq in Purkinje cells evokes production of endocannabinoids, suppresses GABA release, and impairs memory consolidation (Dubois et al. 2020). The latter is prevented by
administration of an endocannabinoid receptor antagonist.
Thus, a learning-induced increase in cerebellar interneuron
activity and GABA release is likely to promote the formation
of associative fear memory.
23.5.4 Receptive Field Plasticity
Cutaneous sensory stimulation activates cerebellar inhibitory interneurons in the C3 zone (Garwicz etal. 1998). The
size of the cutaneous parallel ber receptive elds can be
expanded by conjunctive parallel ber and climbing ber
activation, and is associated with a lasting potentiation of
synaptic currents at the parallel ber to interneurons synapse. In contrast, stimulation of parallel bers alone reduces
the size of the cutaneous receptive elds (Jörntell and Ekerot
2002, 2003). Thus, synaptic plasticity at parallel ber to
interneuron synapses leads to a change in the receptive eld.
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Basket Cells
https://t.me/medicina_free
MasahikoWatanabe
24
Abstract
Basket cells are GABAergic interneurons located in the
basal one-third of the molecular layer of the cerebellum.
Basket cells receive excitatory inputs from granule cells
and cast feed-forward inhibition to Purkinje cells, the sole
output neuron of the cortical region of the cerebellum.
Inhibition of Purkinje cells by basket cells is achieved
chemically by release of the inhibitory transmitter GABA
at somatic synapses and electrically via ephaptic inhibition
in unique structures called by pinceau, which form around
the axon initial segment. This chapter summarizes basic
information on the structure and function of basket cells of
the cerebellum.
Keywords
GABA · Stellate cell · Purkinje cell · Pinceau formation ·
Electrical inhibition
24.1 Introduction
A denitive description of the basket cells of the cerebellum
was provided by Santiago Ramón y Cajal. Ramón y Cajal
discovered a characteristic terminal plexus of basket cells
around Purkinje cell somata, naming this the pericellular
nest or nid. This was the rst clear observation of an axon
terminal in the central nervous system; the discovery cultivated his ideas that nerve cells need only be in contact, not in
continuity, with one another to transmit nerve impulse, and
that the ow of the impulse is directed from the axon of one
cell to the cell body of another. These ideas later came to
fruition as his Neuron Doctrine (Palay and Chan-Palay
1974).
M. Watanabe (*)
Department of Anatomy, Hokkaido University Graduate School of
Medicine, Sapporo, Japan
e-mail: watamasa@med.hokudai.ac.jp
Basket and stellate cells are often collectively called
molecular layer interneurons. Both are GABAergic interneurons that cast feed-forward inhibition to Purkinje cells share
similar developmental, molecular, and ring proles and are
thought to represent a gradually varying cellular continuum
(Zhang and Goldman 1996; Sultan and Bower 1998).
Nevertheless, basket and stellate cells have been distinguished neuroanatomically (Ramón y Cajal 1911; Palay and
Chan-Palay 1974). Basket cells are situated in the basal onethird of the molecular layer and target the soma and axon
initial segment of Purkinje cells (Fig.24.1). In comparison,
stellate cells reside in the supercial two-thirds of the molec-
Fig. 24.1 Golgi staining of cerebellar basket cells in adult mice.
Basket cells are situated in a basal one-third of the molecular layer and
extend moderately straight dendrites (Dn) in the parasagittal plane (this
plane). Basket cell axons (Ax) originate from the soma or from one the
major dendrites of basket cells. Gr granular layer, Mo molecular layer,
PC Purkinje cell layer
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
D. L. Gruol et al. (eds.), Essentials of Cerebellum and Cerebellar Disorders, https://doi.org/10.1007/978-3-031-15070-8_24
169
170
https://t.me/medicina_free
M. Watanabe
ular layer, and target Purkinje cell dendrites. Reecting their
distinct geometrical targeting, the basket-type somatic inhibition powerfully and rapidly inuences on Purkinje cell
spiking output, while the stellate-type dendritic inhibition
counterbalances the parallel ber excitation inlocal regions
of Purkinje cell dendrites (Bower 2010).
24.2 Cytology
The dendrites of basket cells are arborized in the parasagittal plane, and thus they are parallel to those of Purkinje
cells and at right angles to the direction of parallel bers
(Fig.24.1). The axons of basket cells also traverse in the
parasagittal plane, and give off descending axon collaterals.
Axon collaterals originating from 3 to 7 basket cells form
GABAergic perisomatic synapses on individual Purkinje
cells and further embrace the Purkinje cell axon initial segment by constructing the pinceau formation (Sotelo and
Llinas 1972).
24.3 Inputs
The soma and dendrites of basket cells receive excitatory
inputs from parallel bers, the bifurcated axons of granule
cells. Parallel ber–basket cell synapses are formed mostly
on dendritic shafts and occasionally dendritic spines (Palay
and Chan-Palay 1974). Parallel ber–basket cell synapses
show a unique form of long-term synaptic plasticity by
changing postsynaptic AMPA receptors from GluA2lacking (Ca2+-permeable) to GluA2-containing (Ca2+impermeable) receptors (Liu and Cull-Candy 2000).
Parallel ber–basket cell synapses also express the deltatype glutamate receptor GluD1, which strengthens the connectivity of this synapse (Konno etal. 2014). Basket cells
also receive inhibitory inputs from basket and stellate cells,
Lugaro cells, and recurrent Purkinje cell axons (Miyazaki
etal. 2021).
Although several studies reported the presence of
climbing ber-interneuron synapses, their contact lacks
any kind of conventional synaptic specialization (Kollo
etal. 2006). When stimulating climbing bers, no excitatory postsynaptic currents are elicited in molecular layer
interneurons, but interneurons are activated via glutamate
spillover from nearby climbing bers (Szapiro and
Barbour 2007). In turn, molecular layer interneurons send
climbing ber-driven feed-forward inhibition to Purkinje
cells to prolong the post- complex spike pause (Mathews
etal. 2012).
24.4 Outputs
Basket cells form a number of symmetrical synapses on the
soma of Purkinje cells, but such synapses are rare along the
axon initial segment of Purkinje cells (Palay et al. 1968;
Somogyi and Hámori 1976; Iwakura etal. 2012). Molecules
for GABA synthesis and transport are highly concentrated in
basket cell terminals synapsing on Purkinje cell somata, but
are loosely organized in the pinceau formation (Iwakura
etal. 2012). Likewise, GABAA receptor α1 and neuroligin-2,
a synaptic adhesion molecule selective at inhibitory synapses, are highly accumulated on the postsynaptic membrane
of perisomatic basket cell synapses, but virtually lacking in
the axon initial segment (Iwakura etal. 2012). This distinct
organization strongly suggests that the major target of
GABAergic inhibition by basket cell outputs is the soma of
Purkinje cells.
From around birth, climbing bers constitute a dense
plexus around Purkinje cell somata and innervate perisomatic spine-like protrusions or thorns (Ramón y Cajal 1911;
Larramendi 1969). By the end of the second postnatal week
of a rodent’s life, mono-innervation by single climbing bers
is established in most Purkinje cells by dendritic translocation of single “winner” climbing bers and subsequent elimination of perisomatic climbing ber synapses (Hashimoto
etal. 2009). Simultaneously, axon collaterals of basket cells
descend to form inhibitory perisomatic synapses (Larramendi
and Victor 1967) and further construct the pinceau formation
in the third postnatal week (Ango etal. 2004). A subcellular
gradient of the cell adhesion molecule neurofascin guides
basket cell axon collaterals to the specic sites (Ango etal.
2004).
During the reorganization of perisomatic synapses, a considerable fraction of somatic spines innervated initially by
climbing bers are succeeded by basket cell axons and
Bergmann glia, and the switching of postsynaptic receptor
phenotypes from glutamatergic to GABAergic proceeds
under the coverage of basket cell axons (Ichikawa et al.
2011). The establishment of perisomatic basket cell synapses
inuences climbing ber-induced Ca2+ transients in the soma
of Purkinje cells, and regulates the elimination of surplus
climbing ber synapses from Purkinje cell somata
(Nakayama etal. 2012).
24.5 Pinceau Formation
The pinceau formation is composed of nger-like processes
of basket cell axons and astrocytes. Given the strategic location and similarity to the axon cap of teleost Mauthner cells,
24 Basket Cells
https://t.me/medicina_free
171
the pinceau formation is thought to control the ultimate output of Purkinje cells, through either GABAergic inhibition,
electrical inhibition by imposing a passive hyperpolarizing
potential on the axon initial segment (Korn and Axelrad
1980), or both. Unique features of the pinceau formation
have been taken to support the hypothesis of electrical inhibition, an inhibition of action potential generation via the
electrical eld surrounding the Purkinje cell axon initial
segment. The lack of Na+ channels (Laube etal. 1996) and
dense localization of Shaker-type K+ channels KV1.1 and
KV1.2, together with their scaffolding protein PSD-95
(Laube etal. 1996), may prevent active impulse conduction
in the pinceau formation. Similarly, septate-like junctions,
which should create a partially isolated compartment and
provide the pinceau formation with high resistance (Sotelo
and Llinas 1972; Faber and Korn 1989), may allow currents
to preferentially channel into the axon initial segment, thus
leading to passive hyperpolarization. An high-temporal
electrophysiological study demonstrates that the pinceau
formation exerts ultra-rapid axon-axonic ephaptic inhibition, in which electrical elds generated by basket cell
axons alter the excitability of Purkinje cell axon initial segment in a highly compartmentalized structure (Blot and
Barbour 2014). The role of the potassium channel clustering
in ephaptic control over PC spiking has been evidenced
from analysis of Adam11 mutant mice, where Kv1 clusters
are selectively lost from the pinceau formation, not perisomatic axon terminals, and ultrarapid electrical signaling, not
GABAergic chemical signaling, is selectively impaired
(Kole etal. 2015).
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