MECHANISMS AND FUNCTIONAL-SIGNIFICANCE OF A SLOW INHIBITORY POTENTIALIN NEURONS OF THE LATERAL AMYGDALA

A slow inhibitory potential (sIP) elicited upon synaptic activation in spiny, pyramidal-like cells with properties indicative of projection neurons was investigated in slices of the rat and guinea-pig lateral a mygdala in vitro. The sIP succeeded the triphasic sequence of excitato ry and fast/slow inhibitory postsynaptic potentials mediated via gluta mate and GABA(A/B) receptors, respectively, was readily evoked upon re petitive stimulation of the external capsule and appeared to terminate epileptiform burst discharges during pharmacologically reduced GABAer gic influence. The sIP reversed close to the Cl- equilibrium potential , but was not affected by altered transmembrane Cl- gradients and not abolished by antagonists to ligand-gated Cl- channels. Intracellular i njection of QX 314 and resulting blockade of sodium spikes had no effe ct, whereas the Ca2+ chelator BAPTA blocked the sIP concomitantly with slow hyperpolarizing afterpotentials following intrinsically generate d spike firing, thereby indicating the contribution of Ca2+-dependent mechanisms secondary to synaptic activation. During action of BAPTA an d QX 314, an N-methyl-D-aspartate (NMDA) receptor-mediated potential w as unmasked, which contributed to the sIP. The Ca2+-dependent mechanis ms of the sIP involved a membrane K+ conductance, as was indicated by the dependence on the K+ gradient and the shift of the reversal potent ial towards the K+ equilibrium potential during blocked NMDA receptors . During the presence of GABA receptor antagonists, reduction of the C a2+-activated K+ conductance through injection of BAPTA or application of dopamine induced a gradual shift of interictal-like single bursts of spikes towards the generation of re-occurring ictal-like activity. it is concluded that pyramidal-like projection cells in the AL can gen erate a sIP upon synaptic activation, which reflects the combined acti vation of an NMDA receptor-mediated cation current and a K+ current th at is secondary to the rise in intracellular Ca2+ concentration result ing from the preceding depolarizing response. The sIP may play an impo rtant role in controlling excitatory activity in the amygdala, particu larly in preventing the transformation of interictal-like activity tow ards recurrent epileptic discharges during periods of decreased GABAer gic influence.