DIFFERENTIAL-EFFECTS OF ZINC ON HYPERPOLARIZING AND DEPOLARIZING GABA(A) SYNAPTIC POTENTIALS IN HIPPOCAMPAL SLICE CULTURES

We have examined the changes in GABA(A)-mediated synaptic potentials r ecorded from CA3 pyramidal neurons in hippocampal slice cultures follo wing application of zinc (Zn2+). Unlike 4-AP, Zn2+ did not enhance fas t hyperpolarizing potentials but primarily enhanced depolarizing GABA( A) potentials. Zn2+ did not alter the postsynaptic response of pyramid al neurons to pressure applied GABA, consistent with previous reports that Zn2+ enhances the release of GABA from presynaptic terminals. To examine the role of local circuitry in the production of Zn2+ response s, we recorded from cultures maintained for 7-10 days following remova l of the dentate and hilus to allow complete degeneration of the messy fibers (DGX cultures). Zn2+ produced giant depolarizing potentials (G DPs) in DGX cultures that were identical to those in intact cultures. In contrast, the 4-AP response was dramatically altered in DGX culture s. In DGX cultures, Zn2+ co-applied with 4-AP appeared to inhibit the production of fast hyperpolarizing GABAA synaptic potentials produced by 4-AP alone. This inhibition of fast hyperpolarizing potentials sugg ests that Zn2+ may reduce the release of GABA onto pyramidal cell soma ta. These observations suggest that Zn2+ enhances GABA release from lo cal circuit neurons that synapse onto pyramidal cell dendrites, and in hibits GABA release onto pyramidal cell somata.