title: Pre- and postsynaptic contribution of GABAC receptors to GABAergic synaptic transmission in rat collicular slices and cultures.
abstract: The mammalian superior colliculus (SC) is reported to contain gamma-aminobutyric acid (GABA)C receptors (GABACRs) at high concentration. However, their role in GABAergic synaptic transmission is not yet known. The aim of the present study was: (i) to clarify whether GABACRs are activated by endogenous GABA; and (ii), to determine whether GABACRs play a role in inhibitory synaptic transmission. Experiments were performed on acute horizontal slices from the postnatal rat SC or on collicular neurons in dissociated cell culture. In both preparations, bicuculline-resistant current responses to exogenous GABA and currents elicited by cis-4-aminocrotonic acid (CACA) were blocked by (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA), a GABACR antagonist. The CACA-induced currents exhibited a linear current-voltage relationship and reversed at the Cl- equilibrium potential. These results indicate that functional GABACRs are present in the somato-dendritic membrane of collicular neurons. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded using the whole-cell patch clamp technique. TPMPA significantly decreased mIPSC amplitudes in slices, but not in cultured neurons. As TPMPA decreased also the coefficient of variation of mIPSCs, we suggest that somatodendritic GABACRs are located extrasynaptically but can be involved in the generation of IPSCs if GABA diffusion is constrained. In cultures, individual connections were activated by focal electrical stimulation of single neurons, and evoked inhibitory postsynaptic currents (eIPSCs) were recorded. Paired-pulse stimulation revealed that TPMPA significantly decreased the paired-pulse ratio at short (50 ms) interstimulus intervals, and this effect was inversely dependent on the amplitude of the first eIPSC. We conclude that presynaptic GABACRs are activated by endogenous GABA and can alleviate the short-term depression resulting from a preceding episode of GABA release. Thus, in GABAergic synapses of the SC GABACRs are involved in pre- and postsynaptic functions and may therefore contribute to the activity-dependent adjustment of GABAergic inhibition.
authors.affiliation: Developmental Physiology, Johannes Müller Institute of Physiology, Humboldt University Medical School (Charité), Tucholskystrasse 2, 10117 Berlin, Germany. sergei.kirischuk@charite.de
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
authors.forename: Jan
authors.initials: J
authors.lastname: Akyeli
authors.forename: Radu
authors.initials: R
authors.lastname: Iosub
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Grantyn
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D013477:Superior Colliculi / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D018079:Receptors, GABA; D017661:Receptors, Presynaptic; D005680:gamma-Aminobutyric Acid