Differential effects of zinc on hyperpolarizing and depolarizing GABA A synaptic potentials in hippocampal slice cultures

Abstract

We have examined the changes in GABA A-mediated synaptic potentials recorded from CA3 pyramidal neurons in hippocampal slice cultures following application of zinc (Zn 2+). Unlike 4-AP, Zn 2+ did not enhance fast hyperpolarizing potentials but primarily enhanced depolarizing GABA A potentials. Zn 2+ did not alter the postsynaptic response of pyramidal neurons to pressure applied GABA, consistent with previous reports that Zn 2+ enhances the release of GABA from presynaptic terminals. To examine the role of local circuitry in the production of Zn 2+ responses, we recorded from cultures maintained for 7–10 days following removal of the dentate and hilus to allow complete degeneration of the mossy fibers (DGX cultures). Zn 2+ produced giant depolarizing potentials (GDPs) in DGX cultures that were identical to those in intact cultures. In contrast, the 4-AP response was dramatically altered in DGX cultures. In DGX cultures, Zn 2+ co-applied with 4-AP appeared to inhibit the production of fast hyperpolarizing GABA A synaptic potentials produced by 4-AP alone. This inhibition of fast hyperpolarizing potentials suggests that Zn 2+ may reduce the release of GABA onto pyramidal cell somata. These observations suggest that Zn 2+ enhances GABA release from local circuit neurons that synapse onto pyramidal cell dendrites, and inhibits GABA release onto pyramidal cell somata.