GABA-mediated biphasic inhibitory responses in hippocampus

Abstract

γ-Amlnobutyric acid (GABA) can have a biphasic effect on membrane potential when applied to certain central nervous system neurones^1–3. Typically with iontophoresis, this effect is a negative–positive sequence of deflections and both phases are associated with an increase in conductance. However, iontophoretic application of neurotransmitter substances can produce effects even in cases where ordinary synaptic transmitter release is impossible; for example, on dorsal root ganglion cells. Thus, it is important in assessing the physiological relevance of the depolarising GABA response to determine if similar actions are produced synaptically. In addition, although the depolarising aspect of the GABA response has been attributed to activation of dendritic receptors, this identification has remained uncertain. Here, we have used the hippocampal slice preparation to demonstrate that a biphasic inhibitory response results from orthodromic, but not antidromic electrical stimulation in the presence of anaesthetic concentrations of pentobarbital. (For the sake of brevity, we use the term ‘biphasic inhibitory postynaptic potential (i.p.s.p.)’ to describe the response complex, although it seems likely that a combination of two distinct events, rather than two parts of a single event, occurs.) GABA antagonists and tetrodotoxin (TTX) were used to show that the depolarising phase is due to synaptically released GABA acting on dendritic sites in the CA1 region. Both negative and positive phases are associated with a large conductance increase, and both block cell firing, indicating their inhibitory nature. The ionic mechanism of the depolarising phase is not fully understood but seems to involve a chloride conductance increase. Although the functional significance of the depolarising sign of the i.p.s.p. is not clear, the dendritic location would provide very effective control over dendritic excitability.