Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

Abstract

In early postnatal development, perisomatic innervation of cerebellar Purkinje cells (PCs) switches from glutamatergic climbing fibers (CFs) to GABAergic basket cell fibers (BFs). Here we examined the switching process in C57BL/6 mice. At postnatal day 7 (P7), most perisomatic synapses were formed by CFs on to somatic spines. The density of CF-spine synapses peaked at P9, when pericellular nest around PCs by CFs was most developed, and CF-spine synapses constituted 88% of the total perisomatic synapses. Thereafter, CF-spine synapses dropped to 63% at P12, 6% at P15, and Ͻ1% at P20, whereas BF synapses increased reciprocally. During the switching period, a substantial number of BF synapses existed as BF-spine synapses (37% of the total perisomatic synapses at P15), and free spines surrounded by BFs or Bergmann glia also emerged. By P20, BF-spine synapses and free spines virtually disappeared, and BF-soma synapses became predominant (88%), thus attaining the adult pattern of perisomatic innervation. Parallel with the presynaptic switching, postsynaptic receptor phenotype also switched from glutamatergic to GABAergic. In the active switching period, particularly at P12, fragmental clusters of AMPA-type glutamate receptor were juxtaposed with those of GABA A receptor. When examined with serial ultrathin sections, immunogold labeling for glutamate and GABA A receptors was often clustered beneath single BF terminals. These results suggest that a considerable fraction of somatic spines is succeeded from CFs to BFs and Bergmann glia in the early postnatal period, and that the switching of postsynaptic receptor phenotypes mainly proceeds under the coverage of BF terminals.

Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1

“…In the first weeks after birth, perisomatic innervation of PCs switches from excitatory glutamatergic CFs to inhibitory GABAergic BC fibers (BFs) (42). In SCA1, during the first 3 postnatal weeks, mutant ATXN1 exaggerates this switch by markedly increasing GABAergic BC inhibitory inputs (BF innervations).…”

Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination

“…6). In this territory overlap phase, a single winner CF starts dendritic translocation from P9 onwards, whereas the other loser CFs remain on the soma until being eliminated by P15-P17 (4,6,7). It is also during this phase that PF synapses are massively generated (19), and the source of somatic innervation switches from glutamatergic CF synapses to GABAergic basket cell synapses (7), both of which are essential to establish CF monoinnervation (2, 3, 6, 26).…”

“…The soma of a neonatal PC is innervated by more than five CFs with similar synaptic strengths, from which a single CF is functionally strengthened (4,5). The strengthened ("winner") CF starts dendritic translocation, whereas the other weaker ("loser") CFs remaining on the soma are eliminated (6)(7)(8). In this process, P/Q-type voltage-dependent Ca 2+ channels (VDCCs) promote functional differentiation and dendritic translocation of winner CFs, and the early phase of CF synapse elimination (9)(10)(11), whereas the late phase of CF synapse elimination is critically dependent on the formation of parallel fiber (PF) synapses and activation of the type 1 metabotropic glutamate receptor (mGluR1)-protein kinase Cγ (PKCγ) pathway (12)(13)(14)(15)(16)(17).…”

Cav2.1 in Cerebellar Purkinje Cells Regulates Competitive Excitatory Synaptic Wiring, Cell Survival, and Cerebellar Biochemical Compartmentalization

“…4 F). We counted the number of perisomatic CF terminals on the upper half of PC somata, in which most of the perisomatic CF terminals directly attach to the soma without glial intervention Ichikawa et al, 2011). The mean number of VGluT2(ϩ) perisomatic terminals per 100 m of the somatic surface was significantly higher in PC-Ca v 2.1 KO mice (2.4 Ϯ 0.4) than in control mice (0.6 Ϯ 0.1, mean Ϯ SEM, n ϭ 3 mice, p Ͻ 0.05, U test).…”