Dataset Information

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

ABSTRACT: Climbing fibers from the inferior olive make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites and trigger distinctive responses known as complex spikes. We found that, in awake mice, a complex spike in one PC suppressed conventional simple spikes in neighboring PCs for several milliseconds. This involved a new ephaptic coupling, in which an excitatory synapse generated large negative extracellular signals that nonsynaptically inhibited neighboring PCs. The distance dependence of complex spike-simple spike ephaptic signaling, combined with the known CF divergence, allowed a single inferior olive neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over 100 PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicated that such brief PC suppression, as a result of either ephaptic signaling or other mechanisms, could effectively promote firing in neurons in the deep cerebellar nuclei with remarkable speed and precision.

SUBMITTER: Han KS

PROVIDER: S-EPMC7606706 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

Han Kyung-Seok KS Chen Christopher H CH Khan Mehak M MM Guo Chong C Regehr Wade G WG

Nature neuroscience 20200907 11

Climbing fibers from the inferior olive make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites and trigger distinctive responses known as complex spikes. We found that, in awake mice, a complex spike in one PC suppressed conventional simple spikes in neighboring PCs for several milliseconds. This involved a new ephaptic coupling, in which an excitatory synapse generated large negative extracellular signals that nonsynaptically inhibited neighboring PCs. The distance depende ...[more]

PMID: 32895566

Similar Datasets

Project description:Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed during the perinatal period. In the cerebellum of neonatal rodents, each Purkinje cell (PC) receives synaptic inputs from multiple (more than 4) climbing fibers (CFs). During the first 3 postnatal weeks, synaptic inputs from a single CF become markedly larger and those from the other CFs are eliminated in each PC, leading to mono-innervation of each PC by a strong CF in adulthood. While molecules involved in the strengthening and elimination of CF synapses during postnatal development are being elucidated, much less is known about the molecular mechanisms underlying CF synapse formation during the early postnatal period. Here, we show experimental evidence that suggests that a synapse organizer, PTPδ, is required for early postnatal CF synapse formation and the subsequent establishment of CF to PC synaptic wiring. We showed that PTPδ was localized at CF-PC synapses from postnatal day 0 (P0) irrespective of the expression of Aldolase C (Aldoc), a major marker of PC that distinguishes the cerebellar compartments. We found that the extension of a single strong CF along PC dendrites (CF translocation) was impaired in global PTPδ knockout (KO) mice from P12 to P29-31 predominantly in PCs that did not express Aldoc [Aldoc (-) PCs]. We also demonstrated via morphological and electrophysiological analyses that the number of CFs innervating individual PCs in PTPδ KO mice were fewer than in wild-type (WT) mice from P3 to P13 with a significant decrease in the strength of CF synaptic inputs in cerebellar anterior lobules where most PCs are Aldoc (-). Furthermore, CF-specific PTPδ-knockdown (KD) caused a reduction in the number of CFs innervating PCs with decreased CF synaptic inputs at P10-13 in anterior lobules. We found a mild impairment of motor performance in adult PTPδ KO mice. These results indicate that PTPδ acts as a presynaptic organizer for CF-PC formation and is required for normal CF-PC synaptic transmission, CF translocation, and presumably CF synapse maintenance predominantly in Aldoc (-) PCs. Furthermore, this study suggests that the impaired CF-PC synapse formation and development by the lack of PTPδ causes mild impairment of motor performance.

Dataset Information

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

Publications

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets