Serotonin drives a novel GABAergic synaptic current recorded in rat cerebellar purkinje cells: a Lugaro cell to Purkinje cell synapse.
We recorded a novel fast GABAergic synaptic current in cerebellar Purkinje cells in rat brain slices using patch-clamp techniques. Because of a relatively low sensitivity to bicuculline, these currents can be recorded under conditions in which basket and stellate cell inputs are blocked. The observations that the novel synaptic currents occur spontaneously only in the presence of serotonin, and the specific limited positions in the slice from which they can be electrically evoked, suggest that the presynaptic cell is the Lugaro cell. Cell-attached recordings confirm that the Lugaro cell is the only interneuron in the cerebellar cortex with firing behavior consistent with the spontaneous activity recorded in Purkinje cells. The input shows a strong presynaptic modulation mediated by GABA(A) receptors, resulting in a dynamic range from almost 0 to >90% release probability. Modeling GABA(A) receptor responses to different GABA transients suggests that the relatively low sensitivity of the synaptic currents to bicuculline, compared with the higher affinity GABA(A) receptor antagonist SR-95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl) pyridazinium), is attributable to an unusually long GABA dwell time and/or high GABA concentration in the synaptic cleft. The significance of this novel input is discussed in relation to other GABAergic synapses impinging on Purkinje cells. We suggest that the release of GABA onto Purkinje cells from Lugaro cells would primarily occur during motor activity under conditions in which the activity of basket and stellate cells might be inhibited.
Dean
Isabel
I
Department of Physiology, University College London, London WC1E 6BT, United Kingdom.
Robertson
Susan J
SJ
Edwards
Frances A
FA
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002712:Chlorides / Q000378:metabolism*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D002118:Calcium; D001640:Bicuculline