Two distinct types of repetitive bursting activity mediated by NMDA in hypothalamic neurons in vitro

Hypothalamic magnocellular dorsal nucleus neurons were recorded from adult guinea pig brain slices with the whole-cell patch-clamp technique to determ ine the effects of N-methyl-D-aspartate (NMDA) applied in the bath or by io ntophoresis. In a majority of cells (59 of 77, 76.6%), rhythmic bursting di scharges were evoked by specific activation of NMDA receptors when the memb rane was more negative than -60 mV. This endogenous rhythmic activity was r esistant to tetrodotoxin. It was suppressed by removal of extracellular Mg2 +, indicating the involvement of the voltage-dependent block of the NMDA ch annel by Mg2+. Application of thapsigargin showed that rhythmic activity di d not depend on the release of Ca2+ from reticulum stores. Blockers of Ca2 conductances Ni2+ and nifedipine had no effects on the bursts. Their repol arization did not involve the activation of a strophantidin- or ouabain-sen sitive pump, but partly depended on an apamine-sensitive Ca2+-dependent K()current. In a small subset of cells (9 of 69, 13%), specific activation of NMDA receptors induced another type of bursting activity which consisted o f repetitive low-threshold spikes sustaining bursts of action potentials. R hythmic low-threshold spikes subsisted in the presence of tetrodotoxin but were suppressed by Ni2+. Increasing the amount of NMDA brought about a swit ch from the rhythmic low-threshold spike burst firing to the rhythmic burst ing activity observed for the majority of cells. The present data show for the first time that NMDA receptor activation can induce two independent rhy thmic bursting behaviours in the same neuron, probably depending on the str ength of the glutamatergic drive.