The proto-oncogene receptor tyrosine kinase Kit (aliases c-Kit, CD117; human gene symbol KIT, mouse gene symbol Kit) is an evolutionarily conserved, loss-of-function intolerant, gene that is enriched in specific neuron populations and tentatively associated with rare cases of neurological dysfunction (pLI = 0.98 and LOEUF of 0.17) (Figure 1—figure supplement 1A and B; Chen et al., 2022; Bernstein et al., 1990). It is perhaps unsurprising that loss-of-function Kit mutations in humans are rare; Kit is highly pleiotropic, supporting diverse cell populations, including melanocytes, hematopoietic stem/progenitor cells, germ cells, masts cell, and interstitial cells of Cajal (Yarden et al., 1987). Thus, Kit mutations can result in diverse conditions such as hypo- or hyperpigmentation or melanoma, anemia or leukemia, infertility, mastocytosis, and impaired gut motility or gastrointestinal tumors (Kit biology reviewed Bernstein et al., 1990; Lennartsson and Rönnstrand, 2012).

The activation of Kit is stimulated by Kit Ligand (KL) (human gene symbol KITLG, mouse gene symbol Kitl, herein KL), a single-pass transmembrane protein having an extracellular active domain that induces Kit dimerization and kinase activity. Across several decades and species, it has been reported that KL and Kit are mutually expressed in discrete neuron populations known to be connected; it has thus been hypothesized that the expression pattern of KL-Kit may reflect a role in connectivity (Keshet et al., 1991; Motro et al., 1991; Hirota et al., 1992; Manova et al., 1992). Consistent with such a function, case reports have implicated inactivating Kit mutations with disorders of the central nervous system (Telfer et al., 1971; Finucane et al., 1991; Funderburk and Crandall, 1974; Lacassie et al., 1977; Kilsby et al., 2013; Figure 1—figure supplement 1C). Clinical phenotypes include developmental delay, ataxia, hypotonia, intellectual disability, deafness, and autism spectrum disorder. White matter abnormalities have been noted, and limited evidence suggests KL-Kit may indeed regulate axon outgrowth. KL or Kit mutation or pharmacological manipulation alters outgrowth of spinal commissural axons in vitro (Gore et al., 2008), KL stimulates cortical neurite outgrowth in vitro (Su et al., 2013), and Kit reduction in cortex of developing rats or mice delays axon extension (Guijarro et al., 2013). While these reports provide anatomical/morphological data suggesting that KL-Kit influences connectivity, these studies did not address the consequences to neuronal physiology or synaptic connectivity. Functional studies of KL-Kit in synaptic physiology have likely been hampered by pleiotropy and organismal or cell death. Severe global KL-Kit hypomorphs exhibit fatal anemia, and developmental Kit depletion or inhibition in the cerebrum has resulted in the death of neuronal progenitors or nascent neurons (Guijarro et al., 2013; Mashayekhi and Gholizadeh, 2011; Aoki et al., 2017). Therefore, whether KL-Kit is necessary for synaptic function has remained largely unstudied. Here, we address this gap.

In mice, rats, and humans, Kit is abundantly expressed by molecular layer interneurons (MLIs) of the cerebellar cortex (Motro et al., 1991; Hirota et al., 1992; Manova et al., 1992; Kim et al., 2003), while cerebellar KL is restricted to Purkinje cells (PCs), which MLIs provide GABAergic synaptic inhibition to. We tested the hypothesis that PC KL and MLI Kit were essential to the GABAergic inhibition of PCs. We created a Kit conditional knockout mouse and accomplished embryonic knockout of Kit from MLIs; separately, we knocked out KL from postnatal PCs. By either method, disruption of the KL-Kit pair produced robust and specific impairments to GABAergic inhibition of PCs. Through sparse postnatal viral manipulation of KL in PCs, we provide evidence that KL functions throughout adulthood to regulate synaptic function. These results demonstrate that cell-type-specific expression of KL and Kit influences functional connectivity in the mammalian brain, informing the long-observed expression of KL-Kit in the brain and suggesting a rationale for the affiliation of Kit loss with neurological impairment.

We generated mice in which Kit exon 4 is flanked by LoxP sites (Kit tm1c); Kit gene modifications are illustrated in Figure 1C and D. Kit tm1c homozygous Control animals had normal appearance, sex ratios, and reproductive success. Kit protein is abundantly expressed in parvalbumin-positive GABAergic interneurons in the molecular layer of the cerebellar cortex (MLIs), whereas KL is expressed by PCs (Figure 1A and B). To determine if Kit influences synapse function, we conditionally knocked out Kit from MLIs and assessed the MLI:PC synapse. Pax2 is a transcription factor expressed early in the lineage of GABAergic interneurons of the cerebellum (Maricich and Herrup, 1999); a Pax2-Cre transgene enables embryonic recombination (Blake and Ziman, 2014; Pfeffer et al., 2002). We generated Kit tm1c homozygous litters of which nominally half were hemizygous for Pax2 Cre (Kit KO) and half were not (Control). We produced Control and Kit KO animals in normal sex and genotype ratios. As expected for the C57BL/6J background, Control littermates had dark coat and eyes, but littermate Kit KO animals had white whiskers, white fur with variable pigmented patches, and black eyes; example littermates are provided in Figure 1E. Given Pax2 expression in melanocytes (Lee et al., 2011) and the role of Kit in melanogenesis reviewed in Wehrle-Haller, 2003; Besmer et al., 1993, the pigmentation phenotype provided gross confirmation of conditional Kit KO. We thus confirmed that cerebella of Kit KO animals were Kit depleted. By immunohistochemistry in Control animals, we recapitulated the known pattern of Kit immunoreactivity in the parvalbumin-positive MLIs of the cerebellar cortex (Control, Figure 1F and inset). In contrast, a sex-matched Kit KO littermate demonstrated loss of cerebellar Kit immunoreactivity (Kit KO, Figure 1F and inset). In data not shown, we confirmed that both mGlur1/2 and neurogranin-positive cerebellar Golgi cells (which share the MLI Pax2+ lineage, and of which some are transiently Kit positive) were still present in the Kit KO condition (Maricich and Herrup, 1999; Leto et al., 2006; Weisheit et al., 2006; Amat et al., 2017). By western blot of cerebellar lysates from Control animals, Kit resolved as a major band at ~120 kD, but in Kit KO littermates, Kit immunoreactivity was lost; GAPDH as loading control was equivalent, as was parvalbumin (which marks mature MLIs and PCs) (Figure 1G).

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Figure 1—source data 1

Original unedited unlabeled blots for Figure 1G: Kit, GAPDH, and parvalbumin, respectively.

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Figure 1—source data 2

Original unedited unlabeled blots for Figure 1G: Kit, GAPDH, and parvalbumin, respectively.

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Figure 1—source data 3

Original unedited unlabeled blots for Figure 1G: Kit, GAPDH, and parvalbumin, respectively.

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Figure 1—source data 4

Labeled blots for Figure 1G.

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Having validated that Kit KO animals indeed lacked cerebellar Kit, we then assessed the functional impact. We compared spontaneous GABAergic inhibitory postsynaptic currents (sIPSC) in PCs of acute slices generated from ~P34 Control and Kit KO animals, schema (Figure 2A, example traces in Figure 2B). Kit KO was associated with a significant change in the distribution of sIPSC event amplitudes (Figure 2C). For each PC of Control or Kit KO conditions, we calculated the average sIPSC event frequency and amplitude, as well as total inhibitory charge transfer over the recording epoch. We determined there was a significant decrease in sIPSC frequency (Figure 2D) and a less severe decrease of sIPSC amplitude and inhibitory charge. This reduced inhibition did not produce obvious impacts to spontaneous PC firing dynamics: we determined (in 29 Control vs 22 Kit KO cells) that PC membrane potential and membrane resistivity were not significantly different, and that per cell average: spontaneous action potential frequency, inter-spike interval (ISI), and ISI CV2 were not significantly different, despite some difference in the distribution of individual ISI across genotypes.(Figure 2—figure supplement 1). Though circuit consequences of the Kit KO-mediated PC disinhibition were thus not immediately apparent, the reduced sIPSC frequency in Kit KO was not associated with changes in the density or distribution of MLIs or in the thickness of the molecular layer (Figure 2—figure supplement 2).

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Since the number and distribution of MLIs were normal in Kit KO, we sought to determine if the reduced PC inhibition was related to altered MLI physiology (schema, Figure 2—figure supplement 3A). However, capacitance, input resistance, and spontaneous or evoked MLI action potential frequency was not different between Control and Kit KO (Figure 2—figure supplement 3B–E). Since MLI numbers, distribution, and firing were apparently normal in Kit KO, we sought to determine if there were defects in evoked neurotransmitter release. Direct electrode stimulation of the outer or inner molecular layer in a paired-pulse paradigm evoked inhibitory postsynaptic currents (IPSCs) of equivalent mean amplitude in PCs from Control and Kit KO conditions, and we detected no difference in the paired pulse ratio across genotypes (Figure 2—figure supplement 3F–M). These data suggest that electrical stimulation can produce IPSCs of similar amplitude, and that release probability of individual synapses is unchanged, between Control and Kit KO conditions. We therefore investigated markers of the MLI:PC synapses to determine if they were altered.

The density and average size of GABAergic synapses onto PCs (triple-positive VGAT, gephyrin, and calbindin puncta in the molecular layer) was not reduced by Kit KO (example immunofluorescence, Figure 2—figure supplement 4A; quantification, Figure 2—figure supplement 4B and C). MLI axon terminals contribute not just to individual axo-dendritic synaptic puncta, but also to interdigitated MLI axon collaterals around the soma and initial axon segment of PCs, forming ‘pinceaux’ structures. By parvalbumin immunoreactivity, these structures were preserved but smaller in Kit KO (arrowheads, Figure 2—figure supplement 4C), and this was confirmed by decreased Kv1.2 (Figure 2—figure supplement 4D) and PSD-95 (Figure 2—figure supplement 4E). As PSD-95 immunoreactivity faithfully follows multiple markers of pinceaux size (Zhou et al., 2020), we quantified PSD-95 immunoreactive pinceau area and determined that pinceaux size decreased by ~50% in Kit KO (26 Control vs 43 Kit KO pinceau from n of 5 Control vs 8 Kit KO animals, Figure 2—figure supplement 4F). These results suggested that Kit KO MLIs may have defects in physical and/or functional maturation of synapses onto PCs.

To evaluate the number of functional GABAergic synapses, we analyzed miniature synaptic currents in acute cerebellar slices (schema, Figure 2E–G; example traces, Figure 2H–J). In PCs of Kit KO, there was a significant ~50% reduction in the average frequency, but not amplitude, of miniature inhibitory postsynaptic currents (mIPSCs) (Figure 2K). In contrast, the average frequency and amplitude of miniature excitatory postsynaptic current (mEPSC) in PCs from Control and Kit KO did not differ (Figure 2L). These data suggested that Kit KO impaired the MLI:PC synapse but did not rule out a general defect in MLI synapse function. As MLIs synapse not just onto PCs, but also onto other MLIs, we evaluated mIPSCs in MLIs. Mean mIPSC frequency and amplitude in MLIs was unchanged between Control and Kit KO (Figure 2M). Therefore, embryonic MLI Kit KO was associated with a specific defect in the number or proportion of functional GABAergic synapses onto PCs. As MLI Kit and PC KL expression is maintained postnatally, we hypothesized that postnatal postsynaptic PC KL KO would phenocopy embryonic presynaptic MLI Kit KO.

We utilized previously described KL floxed (Ding et al., 2012) and Pcp2-Cre (Barski et al., 2000) strains to yield mice with Control or KL KO PCs (schema, Figure 3A). We confirmed depletion of cerebellar KL transcripts by rtPCR in data not shown (Ding et al., 2012) and that PC KL KO did not grossly disrupt the pattern of Kit immunoreactivity. Patch clamp of PCs in acute slices revealed that PC KL KO produced significant differences in the distribution of sIPSC event amplitudes (example traces, Figure 3B and C). PC KL KO reduced the average sIPSC frequency and amplitude, as well as the total inhibitory charge transfer (‘charge’) recorded in PCs (Figure 3D), without changes to PC capacitance or membrane resistance. The phenotype was specific to GABAergic synapses: there was a substantial reduction in the frequency but not the amplitude of mIPSC events in PCs (Figure 3E). As with Kit KO, we detected no decrease in the per-animal average size or density of triple-positive VGAT/gephyrin/calbindin synaptic puncta in the molecular layer (n = 4 Control vs 4 KL KO animals, mean area 0.249 vs 0.286 µm², p = 0.1962; mean density 0.045 vs 0.046 per µm², p = 0.9658, not illustrated). We further detected no difference in PDS-95+ pinceau area (49 Control vs 48 KL KO pinceaux from n = 4 Control vs 4 KL KO animals, mean area 57.93 vs 53.37 µm², p = 0.6036, not illustrated). Thus, as with embryonic Kit KO, postnatal KL KO apparently reduced the proportion of functional, if not the absolute total number, of GABAergic synapse sites upon PCs. In contrast to this impact on GABAergic synapses, the frequency and amplitude of mEPSCs in KL KO PCs were not different vs Controls (Figure 3F). In data not shown, a KS test revealed a significant difference in the individual mEPSC event amplitude distribution (p = 0.0002, n = 1196 Control vs 1244 KL KO); however, the mean mEPSC amplitude was within 1% between conditions. Similarly, a KS test of mIPSC event amplitudes revealed that the mean mIPSC amplitude was ~10% greater in PC KL KO than in Control (p < 0.0001, n = 5996 Control vs 3958 KL KO). It is therefore unlikely that decreased event amplitude contributed to the specific and robust > 50% decrease in mIPSC frequency detected in PC KL KO. Thus, as with MLI Kit KO, PC KL KO specifically reduced synaptic GABAergic inhibition of PCs.

Figure 3

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Recombination by Pcp2-Cre begins at ~P7 (Barski et al., 2000), whereas Pax2-Cre recombination occurs at ~E15 (Ohyama and Groves, 2004; Maricich and Herrup, 1999). Our results thus suggest that continued expression of the KL-Kit dyad sustains inhibitory drive to PCs. To test this hypothesis (and to avoid transformative effects of Kit overexpression), we tuned KL postnatal expression in vivo.

To determine if acute focal manipulations in KL modulate PC inhibition, we injected replication-defective viruses leveraging the PC-specific L7.6 promoter (Nitta et al., 2017) to express Cre in KL floxed animals, and identified Cre-positive KL KO PCs by mCherry expression (schema, Figure 4A; example transduction, Figure 4—figure supplement 1A–C, E–G). Injections were at P7, P18, or P56; acute slices were generated 2–3 wk after injections. In the P7 neonatal animals, we utilized lentivirus due to its reduced spread vs adeno-associated viral (AAV) particles, which were used for P18 and P56. Patch-clamp recordings in areas of sparse infection revealed that regardless of when KL was depleted, PC KL KO reduced PC sIPSC frequency and inhibitory charge transferred (P7, P18, and P56 in Figure 4—figure supplement 1D, H, and I; P18 injections Figure 4B–D). We next examined the effects of PC KL overexpression using a complementary strategy. We co-injected L7.6 Cre AAV with AAV encoding EF1α-driven Cre-On mCherry and the membrane-bound isoform of mouse KL (mKL2) via a T2A element to produce PC KL overexpression (OX) (schema, Figure 4E). Whether at P18 (shown) or P56 (not shown), KL OX PCs had increased sIPSC frequency, amplitude, and inhibitory charge transferred compared to nearby Control PCs (Figure 4F–H). We noted that Control PCs from the PC KL KO paradigm received a similar degree of inhibition (frequency, amplitude, charge) as did PCs from Sham injections. In contrast, while the KL OX PCs received elevated GABAergic input compared to their adjacent Control PCs, the (KL OX) relative local increase in inhibitory drive was not beyond the level of inhibition recorded in PCs from separate Sham animals (Figure 4F–H). That is, the local gain in synaptic input to KL OX PCs appears to come at the expense of decreasing inhibition to nearby Control PCs.

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For genes essential to survival or reproduction, germline knockout strategies are not feasible for evaluating postnatal physiology. Among such genes, Kit is an example of a highly pleiotropic gene, and so the interpretation of global hypomorphs is challenging and the recombination of conditional alleles outside of desired tissues can lead to lethal or sterile phenotypes. By generating a conditional knockout mouse, we were able to produce viable animals with Kit protein depleted from the cerebellum to reveal a role in synapse function.

MLI number, distribution, action potential firing, and the density of GABAergic synaptic puncta onto PCs are all apparently normal in MLI Kit KO. These data suggest that while MLI axon terminals are present in Kit KO, they may be less functional. An increased failure rate between action potential generation and neurotransmitter release would be consistent with the normal firing frequency and synapse puncta density but decreased sIPSC and mIPSC frequency observed. Under the PPR paradigm, the apparently equivalent evoked responses may be due to direct stimulation of axon terminals and/or simultaneous recruitment of multiple MLIs.

Kit KO most directly impacts the MLI:PC synapse, based on seemingly normal miniature events for parallel fiber: PC synapses (mEPSC in PC) and MLI:MLI (mIPSC in MLI) synapses. This is perhaps expected given the cell-type-specific expression of KL by PCs and Kit by MLIs; however, it is a critical distinction as cerebellins (Zhang et al., 2015) and calsystenin (Liu et al., 2022) impact multiple forms of synaptic input to PCs. It will be informative to determine if the residual inhibitory drive to PCs observed in MLI Kit KO or PC KL KO comes from PC axon collaterals Chan-Palay, 1971; Larramendi and Lemkey-Johnston, 1970; Orduz and Llano, 2007; Witter et al., 2016 whose input we might expect to be preserved if KL-Kit functions primarily to mediate connectivity between different cell types or perhaps from a subtype of interneuron not dependent upon Kit signaling. This distinction is further relevant since our histological analysis of synaptic puncta does not resolve between MLI:PC and PC:PC synapses, the relative balance of which may be altered by either KL or Kit manipulations. Indeed, future studies of the role of KL-Kit on PC-PC connectivity may inform how PC KL OX can apparently weaken inhibition to adjacent PCs: this may occur through the reduction of inhibitory drive from KL OX PCs to adjacent control PCs. An alternative and not mutually exclusive possibility is that PC KL OX excessively potentiates MLI Kit to enhance MLI:MLI inhibition, reducing the inhibitory output surrounding MLIs can provide to control PCs.

Though such important nuances of the circuit mechanisms remain to be elucidated, our results demonstrate that the KL-Kit axis, from embryonic development through young adulthood, can alter GABAergic drive to PCs. These results suggest that KL-Kit may be necessary to maintain, and perhaps capable of modulating, MLI:PC GABAergic inhibition in the adult cerebellum. As each MLI (e.g., basket cell) has axon collaterals that can target multiple PCs, and as each PC can receive input from multiple MLIs, it is interesting to speculate that dynamics (e.g., in the expression or shedding) of KL may act through presynaptic Kit to tune the degree of convergent MLI:PC inhibitory drive. This would complement existing forms of modulation at the MLI:PC synapse, such as those dependent on other PC-derived signaling molecules, like endocannabinoids (Kreitzer et al., 2002; Kreitzer and Regehr, 2001; Safo et al., 2006) or peptides like secretin (Williams et al., 2012; Fuchs et al., 2014) and CR (Wu et al., 2020). The physiology of PCs, and the structure of MLI:PC inhibition, also varies over zones such as those identified by Zebrin-II and PLC β4 (Zhou et al., 2014; Brochu et al., 1990; Leclerc et al., 1990; Sarna et al., 2006; Marzban et al., 2007); whether there is functional variation in KL or Kit expression, signaling, or dependency remains to be determined. Though we have demonstrated a role in synaptic GABAergic inhibition, it is currently unknown whether Kit signaling also plays a role in other forms of inhibition in the cerebellar cortex, such as MLI:MLI gap-junctions, or MLI:PC ephaptic coupling. The latter may be suggested by the Kit KO-mediated reduction in Kv1.1/Kv1.2 and PSD-95 immunoreactivity.

While our data clearly demonstrates that KL-Kit influences synaptic function, we do not yet know the molecular mechanisms involved. Kit is a receptor tyrosine kinase that can activate multiple downstream effectors, including Src family kinases, PLC, PI3K/mTOR, and the MAPK pathway, the latter two notable here for their shared affiliation with synapse phenotypes and autism spectrum disorder. Investigation of the interactome of Kit under basal and KL manipulated conditions may inform the receptor kinase cascades through which Kit signaling sustains synaptic function. It also plausible that trans-cellular interactions between KL and Kit may function in a kinase-independent, cell adhesion molecule modality (Adachi et al., 1992; Tabone-Eglinger et al., 2014). There is a substantial literature illustrating the importance of adhesion molecules in the organization and maintenance of MLI:PC inhibition, such as neurexins/neuroligins, dystrophin/dystroglycan, semaphorins, and neurofascins (Zhang et al., 2015; Liu et al., 2022; Ango et al., 2004; Buttermore et al., 2012; Telley et al., 2016; Cioni et al., 2013; Wu et al., 2022). Much of what is understood about these molecules in the maintenance of PC inhibition is revealed by postsynaptic phenotypes; that is, cis- and trans interacting proteins that, via gephyrin, maintain the organization of PC GABA_A receptors. It is notable therefore that MLI Kit or PC KL KO has a more predominant effect on mIPSC frequency than on amplitude, suggesting a presynaptic phenotype.

Despite the reduced PC inhibition resulting from MLI Kit KO or from PC KL KO, we have not observed overt cerebellar signs (i.e., ataxia). We suspect that this is due to compensation. Even the developmental ablation of functional GABA_A channels in PCs does not produce overt motor signs, while adulthood ablation can (Wisden et al., 2009). Thus, we might unmask behavioral phenotypes if KL or Kit KO is delayed until adulthood. Consistent with the interpretation that developmental compensation may be involved, the impact of postnatal PC KL KO on inhibitory drive to PCs is more pronounced than embryonic MLI Kit KO. Beyond direct inhibition of PCs, MLI:PC GABAergic inhibition constrains granule cell-mediated PC dendritic excitation and thus gates the conversion of PC LTD to LTP at the PF-PC synapse in motor learning (Bonnan et al., 2023; Gaffield et al., 2018). It is therefore possible that KL or Kit KO may only reveal phenotypes in motor learning (or other cerebellar-plasticity dependent) behaviors; speaking to the feasibility of this possibility, global hypomorphs for KL or Kit have altered hippocampal neurophysiology and learning performance on a Water Maze task (Motro et al., 1996; Katafuchi et al., 2000; Kondo et al., 2002). Continuous expression of KL and Kit in specific neurons may thus reflect not only a role in the development (or maintenance) of synaptic function as suggested here but also in the plastic modulation of synaptic strength.

Despite the importance of future works to determine molecular mechanisms and organismal consequences, our study is a discrete advance because it establishes that KL-Kit regulates mammalian central synapse function. Here, we demonstrate impacts at the mouse GABAergic MLI:PC synapse; however, Kit and KL are expressed in diverse organisms and neuronal populations including glutamatergic neurons of the hippocampus, and neurons in olfactory bulb, basal forebrain, and brainstem. It is therefore feasible that the synaptic phenotypes reported here reflect that KL-Kit is broadly capable of influencing connectivity.

In this manuscript, new analysis was performed on previously generated publically accessible dataset(s). The data compilation and analysis was performed by Dr. Jeremy Prokop. The datasets used are detailed at https://doi.org/10.6084/m9.figshare.25000106.v1.

1. 1. Prokop JW

   (2024) figshare

   KIT genomic analysis.

   https://doi.org/10.6084/m9.figshare.25000106.v1

1. 1. Adachi S
   2. Ebi Y
   3. Nishikawa S
   4. Hayashi S
   5. Yamazaki M
   6. Kasugai T
   7. Yamamura T
   8. Nomura S
   9. Kitamura Y

   (1992)

   Necessity of extracellular domain of W (c-kit) receptors for attachment of murine cultured mast cells to fibroblasts

   Blood 79:650–656.

   • PubMed
   • Google Scholar
2. 1. Amat SB
   2. Rowan MJM
   3. Gaffield MA
   4. Bonnan A
   5. Kikuchi C
   6. Taniguchi H
   7. Christie JM

   (2017) Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice

   PLOS ONE 12:e0179347.

   https://doi.org/10.1371/journal.pone.0179347

   • PubMed
   • Google Scholar
3. 1. Ango F
   2. di Cristo G
   3. Higashiyama H
   4. Bennett V
   5. Wu P
   6. Huang ZJ

   (2004) Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment

   Cell 119:257–272.

   https://doi.org/10.1016/j.cell.2004.10.004

   • PubMed
   • Google Scholar
4. 1. Aoki H
   2. Hara A
   3. Kunisada T

   (2017) Induced haploinsufficiency of Kit receptor tyrosine kinase impairs brain development

   JCI Insight 2:e94385.

   https://doi.org/10.1172/jci.insight.94385

   • PubMed
   • Google Scholar
5. 1. Barski JJ
   2. Dethleffsen K
   3. Meyer M

   (2000)

   Cre recombinase expression in cerebellar purkinje cells

   Genesis 28:93–98.

   • PubMed
   • Google Scholar
6. 1. Bernstein A
   2. Chabot B
   3. Dubreuil P
   4. Reith A
   5. Nocka K
   6. Majumder S
   7. Ray P
   8. Besmer P

   (1990)

   The mouse W/c-kit locus

   Ciba Foundation Symposium 148:158–166.

   • PubMed
   • Google Scholar
7. 1. Besmer P
   2. Manova K
   3. Duttlinger R
   4. Huang EJ
   5. Packer A
   6. Gyssler C
   7. Bachvarova RF

   (1993)

   The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in gametogenesis and melanogenesis

   Development 01:125–137.

   • PubMed
   • Google Scholar
8. 1. Blake JA
   2. Ziman MR

   (2014) Pax genes: regulators of lineage specification and progenitor cell maintenance

   Development 141:737–751.

   https://doi.org/10.1242/dev.091785

   • PubMed
   • Google Scholar
9. 1. Bonnan A
   2. Zhang K
   3. Gaffield MA
   4. Christie JM

   (2023) Expression of a form of cerebellar motor memory requires learned alterations to the activity of inhibitory molecular layer interneurons

   The Journal of Neuroscience 43:601–612.

   https://doi.org/10.1523/JNEUROSCI.0731-22.2022

   • PubMed
   • Google Scholar
10. 1. Brochu G
    2. Maler L
    3. Hawkes R

    (1990) Zebrin II: a polypeptide antigen expressed selectively by purkinje cells reveals compartments in rat and fish cerebellum

    The Journal of Comparative Neurology 291:538–552.

    https://doi.org/10.1002/cne.902910405

    • PubMed
    • Google Scholar
11. 1. Buttermore ED
    2. Piochon C
    3. Wallace ML
    4. Philpot BD
    5. Hansel C
    6. Bhat MA

    (2012) Pinceau organization in the cerebellum requires distinct functions of neurofascin in purkinje and basket neurons during postnatal development

    The Journal of Neuroscience 32:4724–4742.

    https://doi.org/10.1523/JNEUROSCI.5602-11.2012

    • PubMed
    • Google Scholar
12. 1. Chan-Palay V

    (1971) The recurrent collaterals of purkinje cell axons: a correlated study of the rat’s cerebellar cortex with electron microscopy and the Golgi method

    Zeitschrift Fur Anatomie Und Entwicklungsgeschichte 134:200–234.

    https://doi.org/10.1007/BF00519300

    • PubMed
    • Google Scholar
13. Preprint

    1. Chen S
    2. Francioli LC
    3. Goodrich JK
    4. Collins RL
    5. Kanai M
    6. Wang Q
    7. Alföldi J
    8. Watts NA
    9. Vittal C
    10. Gauthier LD
    11. Poterba T
    12. Wilson MW
    13. Tarasova Y
    14. Phu W
    15. Yohannes MT
    16. Koenig Z
    17. Farjoun Y
    18. Banks E
    19. Donnelly S
    20. Gabriel S
    21. Gupta N
    22. Ferriera S
    23. Tolonen C
    24. Novod S
    25. Bergelson L
    26. Roazen D
    27. Ruano-Rubio V
    28. Covarrubias M
    29. Llanwarne C
    30. Petrillo N
    31. Wade G
    32. Jeandet T
    33. Munshi R
    34. Tibbetts K
    35. O’Donnell-Luria A
    36. Solomonson M
    37. Seed C
    38. Martin AR
    39. Talkowski ME
    40. Rehm HL
    41. Daly MJ
    42. Tiao G
    43. Neale BM
    44. MacArthur DG
    45. Karczewski KJ
    46. gnomAD Project Consortium

    (2022) A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

    bioRxiv.

    https://doi.org/10.1101/2022.03.20.485034

    • Google Scholar
14. 1. Cioni JM
    2. Telley L
    3. Saywell V
    4. Cadilhac C
    5. Jourdan C
    6. Huber AB
    7. Huang JZ
    8. Jahannault-Talignani C
    9. Ango F

    (2013) SEMA3A signaling controls layer-specific interneuron branching in the cerebellum

    Current Biology 23:850–861.

    https://doi.org/10.1016/j.cub.2013.04.007

    • PubMed
    • Google Scholar
15. 1. Ding L
    2. Saunders TL
    3. Enikolopov G
    4. Morrison SJ

    (2012) Endothelial and perivascular cells maintain haematopoietic stem cells

    Nature 481:457–462.

    https://doi.org/10.1038/nature10783

    • PubMed
    • Google Scholar
16. 1. Finucane B
    2. Scott CI
    3. Kurtz MB

    (1991)

    Concurrence of dominant piebald trait and fragile X syndrome

    American Journal of Human Genetics 48:815.

    • PubMed
    • Google Scholar
17. 1. Flanagan JG
    2. Chan DC
    3. Leder P

    (1991) Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the sld mutant

    Cell 64:1025–1035.

    https://doi.org/10.1016/0092-8674(91)90326-t

    • PubMed
    • Google Scholar
18. 1. Fricano-Kugler CJ
    2. Williams MR
    3. Salinaro JR
    4. Li M
    5. Luikart B

    (2016) Designing, packaging, and delivery of high titer crispr retro and lentiviruses via stereotaxic injection

    Journal of Visualized Experiments 2016:111.

    https://doi.org/10.3791/53783

    • PubMed
    • Google Scholar
19. 1. Fuchs JR
    2. Robinson GM
    3. Dean AM
    4. Schoenberg HE
    5. Williams MR
    6. Morielli AD
    7. Green JT

    (2014) Cerebellar secretin modulates eyeblink classical conditioning

    Learning & Memory 21:668–675.

    https://doi.org/10.1101/lm.035766.114

    • PubMed
    • Google Scholar
20. 1. Funderburk SJ
    2. Crandall BF

    (1974)

    Dominant piebald trait in a retarded child with a reciprocal translocation and small intercalary deletion

    American Journal of Human Genetics 26:715–722.

    • PubMed
    • Google Scholar
21. 1. Gaffield MA
    2. Rowan MJM
    3. Amat SB
    4. Hirai H
    5. Christie JM

    (2018) Inhibition gates supralinear Ca²⁺ signaling in purkinje cell dendrites during practiced movements

    eLife 7:e36246.

    https://doi.org/10.7554/eLife.36246

    • PubMed
    • Google Scholar
22. 1. Gore BB
    2. Wong KG
    3. Tessier-Lavigne M

    (2008) Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target

    Neuron 57:501–510.

    https://doi.org/10.1016/j.neuron.2008.01.006

    • PubMed
    • Google Scholar
23. 1. Guijarro P
    2. Wang Y
    3. Ying Y
    4. Yao Y
    5. Jieyi X
    6. Yuan X

    (2013) In vivo knockdown of cKit impairs neuronal migration and axonal extension in the cerebral cortex

    Developmental Neurobiology 73:871–887.

    https://doi.org/10.1002/dneu.22107

    • PubMed
    • Google Scholar
24. 1. Heintz N

    (2004) Gene expression nervous system atlas (GENSAT)

    Nature Neuroscience 7:483.

    https://doi.org/10.1038/nn0504-483

    • PubMed
    • Google Scholar
25. 1. Hirota S
    2. Ito A
    3. Morii E
    4. Wanaka A
    5. Tohyama M
    6. Kitamura Y
    7. Nomura S

    (1992) Localization of mRNA for c-kit receptor and its ligand in the brain of adult rats: an analysis using in situ hybridization histochemistry

    Brain Research. Molecular Brain Research 15:47–54.

    https://doi.org/10.1016/0169-328x(92)90150-a

    • PubMed
    • Google Scholar
26. 1. Huang EJ
    2. Nocka KH
    3. Buck J
    4. Besmer P

    (1992) Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2

    Molecular Biology of the Cell 3:349–362.

    https://doi.org/10.1091/mbc.3.3.349

    • PubMed
    • Google Scholar
27. 1. Katafuchi T
    2. Li AJ
    3. Hirota S
    4. Kitamura Y
    5. Hori T

    (2000) Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats

    Learning & Memory 7:383–392.

    https://doi.org/10.1101/lm.33900

    • PubMed
    • Google Scholar
28. 1. Keshet E
    2. Lyman SD
    3. Williams DE
    4. Anderson DM
    5. Jenkins NA
    6. Copeland NG
    7. Parada LF

    (1991) Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development

    The EMBO Journal 10:2425–2435.

    https://doi.org/10.1002/j.1460-2075.1991.tb07782.x

    • PubMed
    • Google Scholar
29. 1. Kilsby AJ
    2. Cruwys M
    3. Kukendrajah C
    4. Russell-Eggitt I
    5. Raglan E
    6. Rajput K
    7. Loshe P
    8. Brady AF

    (2013) Homozygosity for piebaldism with a proven KIT mutation resulting in depigmentation of the skin and hair, deafness, developmental delay and autism spectrum disorder

    Clinical Dysmorphology 22:64–67.

    https://doi.org/10.1097/MCD.0b013e32835e8ce5

    • PubMed
    • Google Scholar
30. 1. Kim D
    2. Im JO
    3. Won YJ
    4. Yoon SY
    5. Lee EJ
    6. Lee JH
    7. Hong HN

    (2003) Upregulation of c-Kit receptor and stem cell factor in cerebellar inhibitory synapses in response to kainic acid

    Journal of Neuroscience Research 71:72–78.

    https://doi.org/10.1002/jnr.10466

    • PubMed
    • Google Scholar
31. 1. Kondo T
    2. Katafuchi T
    3. Hori T

    (2002) Stem cell factor modulates paired-pulse facilitation and long-term potentiation in the hippocampal mossy fiber-CA3 pathway in mice

    Brain Research 946:179–190.

    https://doi.org/10.1016/s0006-8993(02)02879-2

    • PubMed
    • Google Scholar
32. 1. Kreitzer AC
    2. Regehr WG

    (2001) Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids

    The Journal of Neuroscience 21:RC174.

    https://doi.org/10.1523/JNEUROSCI.21-20-j0005.2001

    • PubMed
    • Google Scholar
33. 1. Kreitzer AC
    2. Carter AG
    3. Regehr WG

    (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum

    Neuron 34:787–796.

    https://doi.org/10.1016/s0896-6273(02)00695-5

    • PubMed
    • Google Scholar
34. 1. Lacassie Y
    2. Thurmon TF
    3. Tracy MC
    4. Pelias MZ

    (1977)

    Piebald trait in a retarded child with interstitial deletion of chromosome 4

    American Journal of Human Genetics 29:641–642.

    • PubMed
    • Google Scholar
35. 1. Langley KE
    2. Mendiaz EA
    3. Liu NL
    4. Narhi LO
    5. Zeni L
    6. Parseghian CM
    7. Clogston CL
    8. Leslie I
    9. Pope JA
    10. Lu HS
    11. Zsebo KM
    12. Boone TC

    (1994) Properties of variant forms of human stem cell factor recombinantly expressed in Escherichia coli

    Archives of Biochemistry and Biophysics 311:55–61.

    https://doi.org/10.1006/abbi.1994.1208

    • PubMed
    • Google Scholar
36. 1. Larramendi LM
    2. Lemkey-Johnston N

    (1970) The distribution of recurrent purkinje collateral synapses in the mouse cerebellar cortex: an electron microscopic study

    The Journal of Comparative Neurology 138:451–459.

    https://doi.org/10.1002/cne.901380405

    • PubMed
    • Google Scholar
37. 1. Leclerc N
    2. Doré L
    3. Parent A
    4. Hawkes R

    (1990) The compartmentalization of the monkey and rat cerebellar cortex: zebrin I and cytochrome oxidase

    Brain Research 506:70–78.

    https://doi.org/10.1016/0006-8993(90)91200-z

    • PubMed
    • Google Scholar
38. 1. Lee SB
    2. Doberstein K
    3. Baumgarten P
    4. Wieland A
    5. Ungerer C
    6. Bürger C
    7. Hardt K
    8. Boehncke WH
    9. Pfeilschifter J
    10. Mihic-Probst D
    11. Mittelbronn M
    12. Gutwein P

    (2011) PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells

    PLOS ONE 6:e22312.

    https://doi.org/10.1371/journal.pone.0022312

    • PubMed
    • Google Scholar
39. 1. Lennartsson J
    2. Rönnstrand L

    (2012) Stem cell factor receptor/c-Kit: from basic science to clinical implications

    Physiological Reviews 92:1619–1649.

    https://doi.org/10.1152/physrev.00046.2011

    • PubMed
    • Google Scholar
40. 1. Leto K
    2. Carletti B
    3. Williams IM
    4. Magrassi L
    5. Rossi F

    (2006) Different types of cerebellar GABAergic interneurons originate from a common pool of multipotent progenitor cells

    The Journal of Neuroscience 26:11682–11694.

    https://doi.org/10.1523/JNEUROSCI.3656-06.2006

    • PubMed
    • Google Scholar
41. 1. Liu Z
    2. Jiang M
    3. Liakath-Ali K
    4. Sclip A
    5. Ko J
    6. Zhang RS
    7. Südhof TC

    (2022) Deletion of Calsyntenin-3, an atypical cadherin, suppresses inhibitory synapses but increases excitatory parallel-fiber synapses in cerebellum

    eLife 11:e70664.

    https://doi.org/10.7554/eLife.70664

    • PubMed
    • Google Scholar
42. 1. Luikart BW
    2. Schnell E
    3. Washburn EK
    4. Bensen AL
    5. Tovar KR
    6. Westbrook GL

    (2011) Pten knockdown in vivo increases excitatory drive onto dentate granule cells

    The Journal of Neuroscience 31:4345–4354.

    https://doi.org/10.1523/JNEUROSCI.0061-11.2011

    • PubMed
    • Google Scholar
43. 1. Manova K
    2. Bachvarova RF
    3. Huang EJ
    4. Sanchez S
    5. Pronovost SM
    6. Velazquez E
    7. McGuire B
    8. Besmer P

    (1992) c-kit receptor and ligand expression in postnatal development of the mouse cerebellum suggests a function for c-kit in inhibitory interneurons

    The Journal of Neuroscience 12:4663–4676.

    https://doi.org/10.1523/JNEUROSCI.12-12-04663.1992

    • PubMed
    • Google Scholar
44. 1. Maricich SM
    2. Herrup K

    (1999) Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum

    Journal of Neurobiology 41:281–294.

    https://doi.org/10.1002/(sici)1097-4695(19991105)41:2<281::aid-neu10>3.0.co;2-5

    • PubMed
    • Google Scholar
45. 1. Martin FH
    2. Suggs SV
    3. Langley KE
    4. Lu HS
    5. Ting J
    6. Okino KH
    7. Morris CF
    8. McNiece IK
    9. Jacobsen FW
    10. Mendiaz EA

    (1990) Primary structure and functional expression of rat and human stem cell factor DNAs

    Cell 63:203–211.

    https://doi.org/10.1016/0092-8674(90)90301-t

    • PubMed
    • Google Scholar
46. 1. Marzban H
    2. Chung S
    3. Watanabe M
    4. Hawkes R

    (2007) Phospholipase cbeta4 expression reveals the continuity of cerebellar topography through development

    The Journal of Comparative Neurology 502:857–871.

    https://doi.org/10.1002/cne.21352

    • PubMed
    • Google Scholar
47. 1. Mashayekhi F
    2. Gholizadeh L

    (2011) Administration of anti-c-kit antibody into the cerebrospinal fluid leads to increased cell death in the developing cerebral cortex

    Saudi Journal of Biological Sciences 18:261–266.

    https://doi.org/10.1016/j.sjbs.2011.01.006

    • PubMed
    • Google Scholar
48. 1. Motro B
    2. van der Kooy D
    3. Rossant J
    4. Reith A
    5. Bernstein A

    (1991) Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci

    Development 113:1207–1221.

    https://doi.org/10.1242/dev.113.4.1207

    • PubMed
    • Google Scholar
49. 1. Motro B
    2. Wojtowicz JM
    3. Bernstein A
    4. van der Kooy D

    (1996) Steel mutant mice are deficient in hippocampal learning but not long-term potentiation

    PNAS 93:1808–1813.

    https://doi.org/10.1073/pnas.93.5.1808

    • PubMed
    • Google Scholar
50. 1. Nitta K
    2. Matsuzaki Y
    3. Konno A
    4. Hirai H

    (2017) Minimal purkinje cell-specific pcp2/l7 promoter virally available for rodents and non-human primates

    Molecular Therapy. Methods & Clinical Development 6:159–170.

    https://doi.org/10.1016/j.omtm.2017.07.006

    • PubMed
    • Google Scholar
51. 1. Ohyama T
    2. Groves AK

    (2004) Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome

    Genesis 38:195–199.

    https://doi.org/10.1002/gene.20017

    • PubMed
    • Google Scholar
52. 1. Orduz D
    2. Llano I

    (2007) Recurrent axon collaterals underlie facilitating synapses between cerebellar Purkinje cells

    PNAS 104:17831–17836.

    https://doi.org/10.1073/pnas.0707489104

    • PubMed
    • Google Scholar
53. 1. Pfeffer PL
    2. Payer B
    3. Reim G
    4. di Magliano MP
    5. Busslinger M

    (2002) The activation and maintenance of Pax2 expression at the mid-hindbrain boundary is controlled by separate enhancers

    Development 129:307–318.

    https://doi.org/10.1242/dev.129.2.307

    • PubMed
    • Google Scholar
54. 1. Safo PK
    2. Cravatt BF
    3. Regehr WG

    (2006) Retrograde endocannabinoid signaling in the cerebellar cortex

    Cerebellum 5:134–145.

    https://doi.org/10.1080/14734220600791477

    • PubMed
    • Google Scholar
55. 1. Sarna JR
    2. Marzban H
    3. Watanabe M
    4. Hawkes R

    (2006) Complementary stripes of phospholipase Cbeta3 and Cbeta4 expression by Purkinje cell subsets in the mouse cerebellum

    The Journal of Comparative Neurology 496:303–313.

    https://doi.org/10.1002/cne.20912

    • PubMed
    • Google Scholar
56. 1. Skarnes WC
    2. Rosen B
    3. West AP
    4. Koutsourakis M
    5. Bushell W
    6. Iyer V
    7. Mujica AO
    8. Thomas M
    9. Harrow J
    10. Cox T
    11. Jackson D
    12. Severin J
    13. Biggs P
    14. Fu J
    15. Nefedov M
    16. de Jong PJ
    17. Stewart AF
    18. Bradley A

    (2011) A conditional knockout resource for the genome-wide study of mouse gene function

    Nature 474:337–342.

    https://doi.org/10.1038/nature10163

    • PubMed
    • Google Scholar
57. 1. Su Y
    2. Cui L
    3. Piao C
    4. Li B
    5. Zhao LR

    (2013) The effects of hematopoietic growth factors on neurite outgrowth

    PLOS ONE 8:e75562.

    https://doi.org/10.1371/journal.pone.0075562

    • PubMed
    • Google Scholar
58. 1. Tabone-Eglinger S
    2. Calderin-Sollet Z
    3. Pinon P
    4. Aebischer N
    5. Wehrle-Haller M
    6. Jacquier MC
    7. Boettiger D
    8. Wehrle-Haller B

    (2014) Niche anchorage and signaling through membrane-bound Kit-ligand/c-kit receptor are kinase independent and imatinib insensitive

    FASEB Journal 28:4441–4456.

    https://doi.org/10.1096/fj.14-249425

    • PubMed
    • Google Scholar
59. 1. Telfer MA
    2. Sugar M
    3. Jaeger EA
    4. Mulcahy J

    (1971)

    Dominant piebald trait (white forelock and leukoderma) with neurological impairment

    American Journal of Human Genetics 23:383–389.

    • PubMed
    • Google Scholar
60. 1. Telley L
    2. Cadilhac C
    3. Cioni JM
    4. Saywell V
    5. Jahannault-Talignani C
    6. Huettl RE
    7. Sarrailh-Faivre C
    8. Dayer A
    9. Huber AB
    10. Ango F

    (2016) Dual function of nrp1 in axon guidance and subcellular target recognition in cerebellum

    Neuron 91:1276–1291.

    https://doi.org/10.1016/j.neuron.2016.08.015

    • PubMed
    • Google Scholar
61. 1. Wehrle-Haller B

    (2003) The role of Kit-ligand in melanocyte development and epidermal homeostasis

    Pigment Cell Research 16:287–296.

    https://doi.org/10.1034/j.1600-0749.2003.00055.x

    • PubMed
    • Google Scholar
62. 1. Weisheit G
    2. Gliem M
    3. Endl E
    4. Pfeffer PL
    5. Busslinger M
    6. Schilling K

    (2006) Postnatal development of the murine cerebellar cortex: formation and early dispersal of basket, stellate and Golgi neurons

    The European Journal of Neuroscience 24:466–478.

    https://doi.org/10.1111/j.1460-9568.2006.04915.x

    • PubMed
    • Google Scholar
63. 1. Williams MR
    2. Fuchs JR
    3. Green JT
    4. Morielli AD

    (2012) Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum

    The Journal of Neuroscience 32:9228–9237.

    https://doi.org/10.1523/JNEUROSCI.6504-11.2012

    • PubMed
    • Google Scholar
64. 1. Williams MR
    2. DeSpenza T
    3. Li M
    4. Gulledge AT
    5. Luikart BW

    (2015) Hyperactivity of newborn pten knock-out neurons results from increased excitatory synaptic drive

    The Journal of Neuroscience 35:943–959.

    https://doi.org/10.1523/JNEUROSCI.3144-14.2015

    • PubMed
    • Google Scholar
65. 1. Wisden W
    2. Murray AJ
    3. McClure C
    4. Wulff P

    (2009) Studying cerebellar circuits by remote control of selected neuronal types with gaba(a) receptors

    Frontiers in Molecular Neuroscience 2:29.

    https://doi.org/10.3389/neuro.02.029.2009

    • PubMed
    • Google Scholar
66. 1. Witter L
    2. Rudolph S
    3. Lahlaf SI
    4. Regehr WG

    (2016) Purkinje Cell collaterals enable output signals from the cerebellar cortex to feed back to Purkinje Cells and interneurons

    Neuron 91:312–319.

    https://doi.org/10.1016/j.neuron.2016.05.037

    • PubMed
    • Google Scholar
67. 1. Wu WY
    2. Liu Y
    3. Wu MC
    4. Wang HW
    5. Chu CP
    6. Jin H
    7. Li YZ
    8. Qiu DL

    (2020) Corticotrophin-releasing factor modulates the facial stimulation-evoked molecular layer interneuron-purkinje cell synaptic transmission in vivo in mice

    Frontiers in Cellular Neuroscience 14:563428.

    https://doi.org/10.3389/fncel.2020.563428

    • PubMed
    • Google Scholar
68. 1. Wu WC
    2. Bradley SP
    3. Christie JM
    4. Pugh JR

    (2022) Mechanisms and consequences of cerebellar Purkinje Cell disinhibition in a mouse model of duchenne muscular dystrophy

    The Journal of Neuroscience 42:2103–2115.

    https://doi.org/10.1523/JNEUROSCI.1256-21.2022

    • PubMed
    • Google Scholar
69. 1. Yarden Y
    2. Kuang WJ
    3. Yang-Feng T
    4. Coussens L
    5. Munemitsu S
    6. Dull TJ
    7. Chen E
    8. Schlessinger J
    9. Francke U
    10. Ullrich A

    (1987) Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand

    The EMBO Journal 6:3341–3351.

    https://doi.org/10.1002/j.1460-2075.1987.tb02655.x

    • PubMed
    • Google Scholar
70. 1. Zaman T
    2. Lee K
    3. Park C
    4. Paydar A
    5. Choi JH
    6. Cheong E
    7. Lee CJ
    8. Shin HS

    (2011) Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy

    Neuron 70:95–108.

    https://doi.org/10.1016/j.neuron.2011.02.042

    • PubMed
    • Google Scholar
71. 1. Zhang B
    2. Chen LY
    3. Liu X
    4. Maxeiner S
    5. Lee SJ
    6. Gokce O
    7. Südhof TC

    (2015) Neuroligins sculpt cerebellar purkinje-cell circuits by differential control of distinct classes of synapses

    Neuron 87:781–796.

    https://doi.org/10.1016/j.neuron.2015.07.020

    • PubMed
    • Google Scholar
72. 1. Zhou H
    2. Lin Z
    3. Voges K
    4. Ju C
    5. Gao Z
    6. Bosman LWJ
    7. Ruigrok TJH
    8. Hoebeek FE
    9. De Zeeuw CI
    10. Schonewille M

    (2014) Cerebellar modules operate at different frequencies

    eLife 3:e02536.

    https://doi.org/10.7554/eLife.02536

    • PubMed
    • Google Scholar
73. 1. Zhou J
    2. Brown AM
    3. Lackey EP
    4. Arancillo M
    5. Lin T
    6. Sillitoe RV

    (2020) Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes

    eLife 9:e55569.

    https://doi.org/10.7554/eLife.55569

    • PubMed
    • Google Scholar

Author details

1. Tariq Zaman

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Data curation, Investigation, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-1025-8542

2. Daniel Vogt

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Investigation, Writing – review and editing

   Competing interests

   No competing interests declared

3. Jeremy Prokop

   Office of Research, Corewell Health, Grand Rapids, United States

   Contribution

   Data curation, Formal analysis, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1818-9695

4. Qusai Abdulkhaliq Alsabia

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Investigation

   Competing interests

   No competing interests declared

5. Gabriel Simms

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Investigation

   Competing interests

   No competing interests declared

6. April Stafford

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Formal analysis, Investigation, Methodology

   Competing interests

   No competing interests declared

7. Bryan W Luikart

   Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College, Hanover, United States

   Contribution

   Conceptualization, Supervision, Methodology, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-3181-6075

8. Michael R Williams

   Department of Pediatrics & Human Development, College of Human Medicine, Michigan State University, East Lansing, United States

   Contribution

   Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Visualization, Writing – review and editing

   For correspondence

   will3434@msu.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3310-7181

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