Dynamics of fast and slow inhibition from cerebellar golgi cells allow flexible control of synaptic integration.
Throughout the brain, multiple interneuron types influence distinct aspects of synaptic processing. Interneuron diversity can thereby promote differential firing from neurons receiving common excitation. In contrast, Golgi cells are the sole interneurons regulating granule cell spiking evoked by mossy fibers, thereby gating inputs to the cerebellar cortex. Here, we examine how this single interneuron class modifies activity in its targets. We find that GABA(A)-mediated transmission at unitary Golgi cell --> granule cell synapses consists of varying contributions of fast synaptic currents and sustained inhibition. Fast IPSCs depress and slow IPSCs gradually build during high-frequency Golgi cell activity. Consequently, fast and slow inhibition differentially influence granule cell spike timing during persistent mossy fiber input. Furthermore, slow inhibition reduces the gain of the mossy fiber --> granule cell input-output curve, while fast inhibition increases the threshold. Thus, a lack of interneuron diversity need not prevent flexible inhibitory control of synaptic processing.
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
John J
JJ
Crowley
Diasynou
D
Fioravante
Wade G
WG
Regehr
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002461:Cell Line, Transformed; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D010775:Photic Stimulation / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012243:Rhodopsin / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D010879:Piperazines; D011412:Propanolamines; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C085075:CGP 55845A; D012243:Rhodopsin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid