Mechanisms and functional significance of a slow inhibitory potential in 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 amygdala in vitro. The sIP succeeded the triphasic sequence of excitatory and fast/slow inhibitory postsynaptic potentials mediated via glutamate and GABA(A/B) receptors, respectively, was readily evoked upon repetitive stimulation of the external capsule and appeared to terminate epileptiform burst discharges during pharmacologically reduced GABAergic 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 injection of QX 314 and resulting blockade of sodium spikes had no effect, whereas the Ca2+ chelator BAPTA blocked the sIP concomitantly with slow hyperpolarizing afterpotentials following intrinsically generated spike firing, thereby indicating the contribution of Ca2+-dependent mechanisms secondary to synaptic activation. During action of BAPTA and QX 314, an N-methyl-D-aspartate (NMDA) receptor-mediated potential was unmasked, which contributed to the sIP. The Ca2+-dependent mechanisms of the sIP involved a membrane K+ conductance, as was indicated by the dependence on the K+ gradient and the shift of the reversal potential towards the K+ equilibrium potential during blocked NMDA receptors. During the presence of GABA receptor antagonists, reduction of the Ca2+-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 generate a sIP upon synaptic activation, which reflects the combined activation of an NMDA receptor-mediated cation current and a K+ current that is secondary to the rise in intracellular Ca2+ concentration resulting from the preceding depolarizing response. The sIP may play an important role in controlling excitatory activity in the amygdala, particularly in preventing the transformation of interictal-like activity towards recurrent epileptic discharges during periods of decreased GABAergic influence.