Target-dependent feedforward inhibition mediated by short-term synaptic plasticity in the cerebellum.
Cerebellar feedforward inhibition (FFI) is mediated by two distinct pathways targeting different subcellular compartments of Purkinje cells (PCs). The axon of the granule cell, the parallel fiber, makes excitatory synapses not only onto PCs but also onto two types of interneurons, basket and stellate cells. Basket and stellate cells then send inhibitory signals to the soma and dendrites of Purkinje cells, respectively. Functional differences between somatic and dendritic FFI pathways, however, remain unknown. Here we address this question by examining how basket and stellate cells are recruited dynamically under high-frequency granule cell inputs at mice cerebellum. Short-term plasticity of various synapses within the FFI circuit has been explored. Unexpectedly, the parallel fiber synapse, which was considered to be facilitating during repetitive stimulation, shows depression, when the postsynaptic target is a basket cell. Other factors in the FFI circuit, such as firing properties of interneurons and dynamics of inhibitory synapses, are similar between somatic and dendritic pathways. The target-dependent parallel fiber synaptic plasticity has functional consequences for the two FFI pathways, because we observe that PCs receive transient somatic inhibition during 50 Hz stimulation of granule cells but persistent dendritic inhibition.
Bao
Jin
J
Independent Junior Research Group Biophysics of Synaptic Transmission, Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
Reim
Kerstin
K
Sakaba
Takeshi
T
D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D011724:Pyridazines; C485550:Unc13c protein, mouse; C049853:gabazine