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Golgi Neurons
https://t.me/medicina_free
StéphaneDieudonné
25
Abstract
The Golgi cell is an essential cellular component of the
cerebellar cortex and the only source of inhibition to the
billions of granule cells forming the cortical input layer.
Golgi cells are part of feed-forward, feedback, and associative inhibitory circuits onto granule cells. Golgi cells
are thus ideally placed to control the gain and temporal
pattern of granule cell discharge in response to afferent
mossy bers activity. Although several theoretical frames
have been proposed, the impact of Golgi cell activity on
the granular layer encoding capacity is still debated.
Keywords
Interneuron · GABA · Glycine · Inhibitory transmission
Feed-forward inhibition · Feed-back inhibition · Gain
control · Oscillations
25.1 Golgi Cells Within theCerebellar
Microcircuit
25.1.1 Golgi Cell Morphology andDiversity
Golgi cells of the cerebellum, rst described by Camillo
Golgi in 1874 (Golgi 1874), are the main inhibitory interneuron of the granular layer (Eccles et al. 1964; Simat et al.
2007). Golgi cells are the only source of inhibition for bil-
lions of granule cells, which receive on average one inhibitory synapse per dendrite, inside the glomeruli (Jakab and
Hamori 1988). Golgi cells are characterized by their extensive axonal plexus conned to the granular layer (Golgi
1874), with an estimated divergence of 104. Golgi cell axons
S. Dieudonné (*)
Paris, France
e-mail: dieudon@biologie.ens.fr
overlap extensively and many Golgi cell axons converge in
one glomerulus.
Golgi cells are multipolar neurons with four to ten dendrites emerging from their soma. During their course through
the GCL, these basolateral dendrites remain relatively thick
and contorted (Dieudonné 1998). Eventually, one to four
dendrites reach the Purkinje cell layer and divide into thin
apical branches rising through the molecular layer toward
the pial surface (Dieudonné 1998). Apical dendrites may not
cross the boundaries of parasagittal Purkinje cell zebrin-like
bands (Sillitoe etal. 2008), suggesting a modular organization of Golgi cells in the cerebellar microcircuit.
Golgi cells are neurochemically diverse. The majority of
Golgi cells stain for the two inhibitory amino acids GABA
and glycine but about 20% contain GABA Gammaaminobutyric acid (GABA) only (Simat etal. 2007). Golgi
cells can exert functional mixed GABA Gamma-aminobutyric
acid (GABA)/glycine inhibition on one of their minor target,
the Unipolar Brush Cell (Dugué 2005), but granule cells
express only GABA-A receptors (Brickley etal. 1996), questioning the role of glycine at this synapse. Immunostainings
for various markers have further highlighted the diversity of
Golgi cells (Geurts et al. 2003). Strikingly, neurogranin
labels all Golgi cells expressing the GABA synthesis enzyme
GAD67, while mGluR2 is expressed in all glycinergic Golgi
cells (Simat et al. 2007). The neurochemical diversity of
Golgi cells provides evidence for the complexity of granule
cell’s inhibitory control.
25.1.2 Excitatory Synaptic Inputs toGolgi
Cells
Golgi cells receive three types of excitatory inputs. Mossy
bers (MF) contact the basolateral dendrites of Golgi cells
within the glomeruli (Palay and Chan-Palay 1974; Cesana
et al. 2010), forming a feed-forward inhibitory circuit on
granule cells. The ascending axons of granule cells make
© 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_25
173
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S. Dieudonné
synapses on the somata and dendrites of Golgi cells, on their
way to the molecular layer (ML) (Cesana etal. 2010). These
numerous contacts provide the anatomical substrate for a
feedback inhibitory circuit, whereby granule cells can evoke
fast retroactive inhibition from local Golgi cells. Finally, the
parallel bers of distant granule cells contact the apical dendrites of Golgi cells in the molecular layer (Cesana et al.
2010; Palay and Chan-Palay 1974). This associative circuit
could coordinate the level of activity among distant parasagittal modules along parallel ber beams (Vos etal. 1999a).
Climbing bers do not contact Golgi cells (Galliano et al.
2013).
All three excitatory synapses on Golgi cells contain
AMPA and NMDA receptors (Dieudonné 1998; Cesana
etal. 2010; Kanichay and Silver 2008). Glutamate spillover
generates a slow component of the AMPA excitatory postsynaptic currents (EPSCs) (Kanichay and Silver 2008;
Cesana et al. 2010) at morphologically complex MF synapses within the glomerulus. AMPA receptors at ascending
axon synapses decay with a single fast component
(Dieudonné 1998; Cesana etal. 2010), but distal PF EPSCs
are passively ltered by the thin apical dendrites of Golgi
cells (Dieudonné 1998; Vervaeke etal. 2012).
granular layer to match ongoing MF activity (Marr 1969;
Billings et al. 2014). The activity of Golgi cells is indeed
modulated with brain state and sensorimotor performance
(Edgley and Lidierth 1987; Prsa et al. 2009; Heine et al.
2010) invivo.
25.2.2 Combinatorial Pattern Enrichment
The overlap and convergence of many Golgi cells in the
granular layer creates in the granule cell population a rich
combination of possible inhibitory inputs, which could
enrich granule cells activity patterns (Mapelli etal. 2010).
The presence of receptive elds for Golgi cell responses supports this hypothesis (Edgley and Lidierth 1987; Prsa etal.
2009; Heine et al. 2010; Vos et al. 1999b). Computational
models have attempted to extend this hypothesis to the temporal domain (Yamazaki and Tanaka 2007). This temporal
hypothesis is supported by the complex time course of Golgi
cell responses to peripheral stimulations (Holtzman 2006;
Vos etal. 1999b).
25.1.3 Inhibitory Synaptic Inputs toGolgi Cells
Lugaro cells provide a major inhibitory input to Golgi cells
via their parasagittal and longitudinal axonal plexus in the
ML (Dumoulin etal. 2001; Lainé and Axelrad 1996). Mixed
inhibitory transmission is the rule at this synapse in the rat
(Dumoulin et al. 2001). Lugaro cell synapses are ideally
placed to shunt Golgi cells apical dendrites and could participate to the synchronization of Golgi cells along PFs observed
invivo (Vos etal. 1999a). Surprisingly, Golgi cells are neither contacted by Purkinje cells nor by ML interneurons.
However, they contact each other with a probability of 20%
(Hull and Regehr 2012).
25.2 Golgi Cell Function
The main function of the granular layer is to expand and
separate the patterns of mossy ber activity (Marr 1969).
Golgi cells, the ablation of which causes ataxia (Watanabe
et al. 1998), have been proposed to participate in several
ways in the enrichment of granular layer patterns.
25.2.3 Temporal Windowing andOscillations
Finally, Golgi cells may sharpen the temporal response of
granule cells to MF inputs by providing feed-forward and
feedback inhibition (D'Angelo and De Zeeuw 2009). This
temporal windowing may occur on the slower timescale of
theta/beta oscillations, for which Golgi cells show resonance
thanks to their gap-junction connections (Dugué etal. 2009)
and intrinsic excitability (Solinas etal. 2007).
25.3 Conclusion
While our knowledge of the connectivity of Golgi cells
within the cerebellar microcircuit has greatly improved,
much remains to be understood of the functional role of
Golgi cells. The putative existence of multiple Golgi subtypes is of particular interest for future investigations.
Acknowledgements This work was supported by the ANR grant
INNET to S.D.
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Lugaro Cells
https://t.me/medicina_free
MoritoshiHirono
26
Abstract
Lugaro cells, which have typical spindle-shaped cell
bodies, were discovered in the cerebellar granule cell
layer more than 100years ago. Although their electrophysiological properties have recently been investigated,
Lugaro cell characteristics have not been well established. This chapter will review the morphological and
electrophysiological characteristics of Lugaro cells and
globular cells, a subgroup of Lugaro cells. A Lugaro/
globular cell- incorporated microcircuit, which could
contribute to cerebellar motor coordination, will also be
introduced.
Keywords
Globular cell · Calretinin · Serotonin · Noradrenaline
Axon collateral · Microcircuit
26.1 Introduction
Characterizing individual cells and their synaptic connections in the cerebellum helps to understand the mechanisms
underlying cerebellar motor coordination (Ito 2011). The
canonical neuronal network of the cerebellar cortex consisted of only ve types of neurons: Purkinje cells (PCs),
granule cells, Golgi cells, basket cells, and stellate cells.
However, recent evidence suggests that inhibitory interneurons in the cerebellar cortex are more heterogeneous than
those named in traditional classication (Lainé and Axelrad
1994, 2002; Melik-Musyan and Fanardzhyan 2004; Crook
etal. 2006; Simat etal. 2007; Schilling etal. 2008; Prestori
et al. 2019; Kozareva et al. 2021). The Lugaro cell is an
example of such interneurons. Lugaro cells were rst
M. Hirono (*)
Department of Physiology, Wakayama Medical University,
Wakayama-shi, Wakayama, Japan
e-mail: mhirono@wakayama-med.ac.jp
described in the cat cerebellum as a unique morphologically
distinct interneuron located underneath the PC layer or
within the granule cell layer (Lugaro 1894).
26.2 Morphological Characteristics
ofLugaro/Globular Cells
Typical Lugaro cells have spindle-shaped cell bodies with
dendrites extending from both sides of the soma (Lugaro
1894; Fox 1959; Fig.26.1a), and axons extending into the
molecular layer, along the mediolateral direction parallel to
the parallel bers (Palay and Chan-Palay 1974; Lainé and
Axelrad 1996). Lugaro cells are glycinergic/GABAergic
interneurons that express the calcium-binding protein, calretinin, at a relatively higher level than other cerebellar neurons. Hence, an anti-calretinin antibody has been used for
immunohistochemical characterization of Lugaro cells
(Rogers 1989; Arai etal. 1991). There are a small number of
Lugaro cells in the cerebellar cortex (Sahin and Hockeld
1990) and the ratio per PC is 1:15in the rat cerebellar cortex
(Dieudonné and Dumoulin 2000). In the rat vermis, Lugaro
cell bodies are distributed more abundantly in the posterior
lobules (VII–X) and are often identied in the sulcus
between the lobules, but rarely at the apex of the lobules
(Dieudonné 2001). Lugaro cells are divided into two subgroups based on their cell body morphology: fusiform
Lugaro cells and globular cells, which have a small and
globular-shaped cell body (Lainé and Axelrad 2002; Simat
et al. 2007; Schilling et al. 2008; Hirono et al. 2012).
Although specic chemical markers for Lugaro/globular
cells have not yet been identied, antibodies against Rat303,
Kv4.3, mGluR1α, SMI311, and chondroitin sulfate proteoglycan have been used for their detailed anatomical studies
(Sahin and Hockeld 1990; Geurts etal. 2001; Hsu et al.
2003; Víg etal. 2003; Crook etal. 2007; Hirono etal. 2021).
A recent transcriptomic study suggested the combined
expression of markers for putative Lugaro cells (Htr2a and
© 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_26
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a b
M. Hirono
Fig. 26.1 Morphology of the Lugaro cell and Lugaro/globular cellincorporated microcircuit. (a) A typical fusiform Lugaro cell (arrow) in
a sagittal cerebellar slice derived from a GAD67
expressing GFP (green uorescent protein) specically in the
GABAergic neurons. Scale bar, 50μm. (Modied from Ito 2011). (b) A
schematic diagram of the microcircuit including Lugaro/globular cells.
+/GFP
knock-in mouse
Edil3) and putative globular cells (Aldh1a3 and Slc6a5)
(Kozareva etal. 2021). Additionally, neurochemical differences in Lugaro/globular cells between species have been
reported. Avian Lugaro cells lack calretinin but express a
different calcium-binding protein, secretagogin (Craciun
etal. 2019). Lugaro cells contain atrial natriuretic peptide
(ANP) in the human cerebellum (McKenzie etal. 2001) and
nicotinamide adenine dinucleotide phosphate-diaphorase
(NADPH-d), which is a surrogate marker for neuronal nitric
oxide synthase (nNOS) in the cerebellum of rabbits and
teleost sh (Okhotin and Kalinichenko 2000; Pushchina and
Varaksin 2001). These results suggest that ANP and NO
released from Lugaro cell dendrite terminals that contact
microvessel walls may contribute to the dilation of cerebellar microvessels (Kalinichenko and Pushchin 2018),
whereas expression of NADPH-d in Lugaro cells is not conserved among other mammals and birds (Craciun et al.
2019). The comparative morphology of Lugaro cells in
large-brained mammalian species has demonstrated that
Lugaro cells in the elephant cerebellum are disproportionately larger than those in other species (Jacobs etal. 2014),
suggesting that elephant Lugaro cells with dendrites extending longer in the sagittal plane could receive more local synaptic inputs and integrate them, leading to inhibit their
targets located at farther distances.
The Lugaro/globular cells receive excitatory synaptic inputs from the
mossy bers (MF), climbing bers (CF), and the axons of the granule
cells (GrC). Serotonin elicits robust ring in both the Lugaro cells (LC)
and globular cells (GlC), while noradrenaline induces ring only in the
GlCs. PC Purkinje cell, BC basket cell, SC stellate cell, GoC Golgi cell.
(Modied from Hirono etal. 2012)
26.3 Physiological Characteristics
ofLugaro/Globular Cells
Due to the small number of Lugaro cells present, it is difcult to identify the soma of these cells under Nomarski optical microscopy. Moreover, the size of their cell bodies is
similar to that of Golgi cells, which have a similar location in
the cerebellar cortex. Whole-cell patch-clamp recordings
were nally applied to Lugaro cells in rat acute cerebellar
slices to observe the electrical responses to serotonin
(5-hydroxytryptamine, 5-HT) (Dieudonné and Dumoulin
2000). Electrophysiological characterization of Lugaro/
globular cells showed robust ring, elicited by 5-HT, while
they were normally silent at rest (Dieudonné and Dumoulin
2000; Dumoulin etal. 2001; Dean etal. 2003; Hirono etal.
2012). This suggests that Lugaro/globular cells are the pri-
mary targets of 5-HT released from serotonergic axon terminals in the cerebellar cortex. The 5-HT-induced robust ring
could be mediated by the activation of 5-HT2 and 5-HT6
receptors (Dieudonné 2001). In the case of globular cells,
action potential ring is elicited by an agonist for 5-HT2A but
not 5-HT2C or 5-HT6 receptors (Hirono et al. 2017).
Furthermore, unlike fusiform Lugaro cells, globular cells
show ring facilitation by another monoamine, noradrenaline (NA) (Hirono etal. 2012).
26 Lugaro Cells
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Lugaro/globular cells display higher inhibitory synaptic
activity than Golgi cells (Dieudonné 2001; Hirono et al.
2012; Eyre and Nusser 2016). Since the somata and proxi-
mal dendrites of Lugaro/globular cells are surrounded by the
axon collateral terminals of PCs, labeled by the calbindinantibody, Lugaro/globular cells likely receive recurrent PC
axon collaterals (Lainé and Axelrad 2002; Crook etal. 2007;
Simat etal. 2007). Experiments using electrophysiology and
optogenetics have demonstrated that PCs make functional
GABAergic synaptic contacts with Lugaro/globular cells,
suggesting that outputs from several PCs converge on a
Lugaro/globular cell in the cerebellar cortex (Hirono etal.
2012; Witter etal. 2016). These contacts are not attenuated
by the activation of presynaptic cannabinoid receptors compared to their blocking effect on GABAergic transmission
between basket/stellate cells and PCs (Witter et al. 2016;
Hirono and Yanagawa 2021). Lugaro cells express α1
subunit- containing GABAA receptors, while Golgi cells
express α3 subunits. Lugaro/globular cells show fast decay
times of miniature inhibitory postsynaptic currents, which
are enhanced by zolpidem, a selective positive allosteric
modulator for α1 subunit-containing GABAA receptors
(Hirono etal. 2012; Eyre and Nusser 2016). Thus, GABAergic
input-mediated dendritic ltering of Lugaro/globular cells is
distinct from that of Golgi cells. The 5-HT and NA released
in the cerebellar cortex can suppress the strong PC-mediated
inhibition onto Lugaro/globular cells through the activation
of presynaptic 5-HT1B receptors and α2 adrenoceptors,
respectively (Hirono etal. 2017). This monoaminergic disinhibition could make the neurons more burst ring when
5-HT is released to Lugaro/globular cells and NA to globular
cells. Minor inhibitory synaptic transmission from Golgi
cells and Lugaro/globular cells to Lugaro/globular cells has
been also demonstrated morphologically (Simat etal. 2007;
Miyazaki etal. 2020).
In contrast, Lugaro/globular cells receive a small number
of fast glutamatergic excitatory synaptic inputs (Dieudonné
2001; Hirono etal. 2012). The excitatory synaptic inputs in
globular cells do not show paired-pulse facilitation but
paired-pulse depression only at short interpulse intervals
(<100ms). These results are similar to those observed at synapses between mossy bers and Golgi cells or mossy bers
and granule cells (Xu-Friedman and Regehr 2003; Kanichay
and Silver 2008), and are different from those at synaptic
connections of climbing ber PCs (Dittman and Regehr
1998). These ndings indicate that Lugaro/globular cells
receive mossy ber inputs (Hirono et al. 2012). Although
immunouorescence and immunoelectron microscopy have
suggested that climbing bers and granule cell axons also
form contacts with the soma and dendrites of Lugaro cells
(Miyazaki etal. 2021), these excitatory synaptic connections
with Lugaro/globular cells have not been well established
physiologically. In vivo two-photon calcium imaging of
Lugaro/globular cells was performed using genetically
encoded calcium indicators and demonstrated that facial airpuff stimulation increased the calcium concentration of
Lugaro/globular cell somata and dendrites to a greater extent
than in Golgi cells in awake mice (Kuhn etal. 2012). The
calcium signals showed steep increases and continued to
increase after the puff offset until it reached a plateau, followed by a slow decrease. Compared to the responses of
Lugaro/globular cells, the calcium signals in Golgi cells
showed a small and slow rise during airpuff stimulation with
an immediate decrease just after the puff offset. To elucidate
the physiological roles of Lugaro/globular cells in cerebellar
local networks and motor coordination, a combination of
electrophysiology and imaging recordings is required.
The parasagittal axonal plexus of Lugaro/globular cells
contact basket/stellate cells, and the long transverse branches
(~2mm) of Lugaro/globular cells make functional connections with Golgi cells (Lainé and Axelrad 1998, 2002;
Dieudonné and Dumoulin 2000; Dumoulin etal. 2001; Simat
etal. 2007; Schilling etal. 2008; Fig.26.1b). One Golgi cell
receives inhibitory synaptic inputs from approximately 10
Lugaro cells. Moreover, each Lugaro cell presumably makes
synaptic contacts divergently with around 150 Golgi cells
(Dieudonné and Dumoulin 2000; Dieudonné 2001;
Dumoulin et al. 2001). Thus, there is a possibility that
Lugaro/globular cells can synchronize activity among Golgi
cells. Although Lugaro/globular cells have also been proposed to synaptically inhibit PCs (Dean etal. 2003), the possibility has been denied by a recent morphological study
(Miyazaki etal. 2021).
26.4 Possible Physiological Meanings
Lugaro/globular cells form a cerebellar transverse microcircuit that involves not only PC-Lugaro/globular cell pairing
but also the other connections between Lugaro/globular
cells and basket/stellate cells and Golgi cell-granule cell
pairs (Dieudonné 2001; Simat et al. 2007; Hirono et al.
2012). The basal ring of PCs can regulate the membrane
excitability of Lugaro/globular cells through the PC-Lugaro/
globular cell feedback loop. The ring of Lugaro/globular
cells, elicited by excitatory synaptic or monoaminergic
inputs, therefore, recties the ring of PCs (Strahlendorf
etal. 1984). The transversal inhibitory outputs from Lugaro/
globular cells may consequently synchronize the activity of
PC clusters in different microzones. In awake and active
animals, the ring of serotonergic neurons in the raphe
nuclei and of noradrenergic neurons in the locus coeruleus
is more facilitated. Thus, the monoaminergic excitatory
effects on Lugaro/globular cells could contribute to cerebellar motor coordination through the optimization of multiple
muscle activity.
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M. Hirono
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Unipolar Brush Cells
https://t.me/medicina_free
MarcoMartina andGabriellaSekerková
27
Abstract
The unipolar brush cells (UBCs) are excitatory interneurons in the granule cell layer of the cerebellar cortex.
They represent a relay station that amplies extracerebellar inputs from vestibular origin as well as other
inputs whose origin remains the focus of ongoing
research. In adult animals, the UBCs are broadly classied into two functionally and chemically distinct subclasses. Type I UBCs, characterized by calretinin
expression, are regularly ring, express type 2 metabotropic glutamate receptors (mGluR), and are located in
lobules IX and X.Type II UBCs are characterized by the
expression of mGluR1α, which mediates a long-lasting
excitatory response to mossy ber inputs. Type II UBCs
are burst ring and are present throughout the cerebellar
cortex, although their expression is greatly enriched in the
vestibulocerebellum. Both UBC types show peculiarly
slow glutamatergic currents in response to synaptic activation. This electrophysiological property suggests a critical role for these cells in determining the timing of the
response of the cerebellar cortex to peripheral inputs.
Recent data also suggest that dysfunction of cerebellar
UBCs has a pathogenic role in a subset of cerebellar ataxias and represents a potential cellular substrate for the
generation of tinnitus.
Keywords
Vestibulocerebellum · Ataxia · Tinnitus · Microcircuitry ·
Mossy bers
M. Martina (*) · G. Sekerková
Department of Neuroscience, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA
e-mail: m-martina@northwestern.edu;
g-sekerkova@northwestern.edu
27.1 Morphology andSpatial Distribution
UBCs are small excitatory interneurons of the cerebellum
and cochlear nuclear (CN) complex (Bell et al. 2008;
Mugnaini etal. 2011). Morphologically, they are dened by
one short dendrite terminating in a brush of ne dendrioles,
which form a specialized giant synaptic junction with a single mossy ber terminal. Each UBC axon terminates in several mossy ber rosettes so that UBC axons generate a web
of intrinsic mossy bers superimposed on the canonical
extrinsic mossy ber system (Nunzi and Mugnaini 2000;
Mugnaini etal. 2011). Thus, the morphological properties of
UBCs are well suited to amplify input signals that can be
transmitted through their extended intrinsic mossy ber network to downstream granule cell clusters and create a feedforward amplication system for sensory afferents. UBCs
are already present in Teleostei and are virtually unchanged
in all mammals, including humans (Mugnaini etal. 2011).
Intriguingly, their density increases with phylogenetic evolution as the density of these cells is considerably higher in
monkeys compared to rodents (Takács etal. 1999).
27.2 UBC Subtypes
Even though recent gene expression shows continuous variation in gene expression among UBCs (Kozareva etal. 2021),
the UBC population can be broadly classied into two chemically and functionally distinct subclasses, calretinin-positive
type I and mGluR1α-positive type II UBCs (Kim etal. 2012;
Sekerková etal. 2014). The topographical distributions of
the two UBC subtypes overlap only in part, as type II cells
are widely distributed across cerebellar lobules while expression of type I UBCs is mostly limited to the vestibulocerebellum (Fig.27.1; Mugnaini etal. 2011; Sekerková etal. 2014).
A study in acute cerebellar slices examined the electrophysiological properties of the two UBC subclasses (Kim etal.
2012). This study showed that type I UBCs are intrinsically
© 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_27
181
182
ab
cd
ef
https://t.me/medicina_free
M. Martina and G. Sekerková
Fig. 27.1 Distribution of the cerebellar UBCs. (a, b) Density map of
type I (a) and type II (b) UBCs distribution in mouse cerebellum based
on calretinin and mGluR1α immunostaining, respectively. Insets show
immunolabeling of the UBCs with these antibodies. (c, d) Images from
of mouse cerebellar cortex illustrate the absence of type I UBCs in lob-
ule V (c). Type II UBCs are also rare in this lobule (d, arrowheads). (e,
f) In contrast to the mouse, the cerebellar cortex of Rhesus monkey
contains UBCs in all lobules and at higher density. For comparison with
mouse cerebellum lobule V is shown. Several type I (e) and type II (f)
UBCs are indicated by arrowheads
27 Unipolar Brush Cells
https://t.me/medicina_free
183
ring and show a nearly monotonic input/output function
over a relatively large input range and thus can provide a
ne-tuned, linear amplication of the vestibular inputs. In
contrast, type II UBCs are often silent and exhibit burst ring
when stimulated (Diana etal. 2007, Kim etal. 2012); therefore, any input large enough to cross the threshold will lead
to a burst of action potentials, potentially enhancing the
downstream signal. These ndings suggest that UBC diversity is likely critical for appropriate network function. In line
with this suggestion, more recent data show that, based on
their differential response to glutamatergic inputs, type I and
type II UBCs may be considered functional equivalents of
“OFF” and “ON” retinal cells, respectively (Borges-Merjane
and Trussell 2015).
27.3 UBC Connectivity
Although the different electrophysiological properties suggest that the two UBC subclasses have different functional
roles, knowledge of the inputs and outputs of the UBC subtypes remains incomplete (Fig.27.2). Because type I UBCs
are selectively expressed in the vestibulocerebellum
(Sekerková etal. 2014), and their distribution is in register
Fig. 27.2 UBC circuitry in the vestibulocerebellum. In the classical
cerebellar circuitry (orange, illustrated on the far left side of the schematic) extrinsic mossy ber terminals connect with granule cells (Gc),
which in turn relay the input to Purkinje cells. UBCs modify the classical circuitry by introducing a further node between afferent bers and
granule cells (reviewed in Mugnaini etal. 2011). Moreover UBCs provide a parallel unconventional intrinsic mossy ber system (dashed
arrows) superimposed on the extrinsic system. The schematic illustrates
both known vestibulocerebellar (green- and red-colored UBCs) and
hypothesized (grey- colored UBCs) circuitries. Yellow UBCs represent
second order UBCs. Type I (“OFF”) UBCs are shown in red, and type
II (“ON”) in green. Throughout the schematic, black dots represent
(inhibitory) inputs from Golgi cells
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