NMDA receptor-mediated changes of spontaneous activity patterns in thalamocortical slice cultures

Spontaneous activity is a hallmark of the thalamocortical system in vivo. Up until now, in vitro preparations of this system have been shown to be spontaneously active only when inhibition was reduced or N-methyl-D-aspartate (NMDA) receptor-mediated currents were facilitated via low extracellular magnesium levels. This study investigated the dependence of spontaneous thalamocortical activity patterns on NMDA receptor function via variation of extracellular magnesium levels (0-1 mM) and by the application of the specific NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (AP5) in the absence of magnesium. We used cocultures of rat neocortical and thalamic slices which have been shown to develop reciprocal synaptic connections similar to those in vivo. Multi-site extracellular recordings revealed that the cultures were spontaneously active at all concentrations of magnesium and AP5, albeit with a high variability among cultures. Activity consisted of burst-like events which were largely synchronized within as well as among the neural tissues, and thalamic background activity during periods of neocortical quiescence. Each tissue was capable of triggering activity in the other, indicating that both thalamocortical and corticothalamic synaptic connections were functional. With increasing magnesium concentration, activity rates declined in both tissues and the site of origin of the synchronous, burst-like events shifted from neocortex to thalamus. AP5 in magnesium-free perfusion solution had qualitatively similar effects. We conclude that thalamic activity is not as dependent on the facilitation of NMDA receptor-mediated currents as neocortical activity and consequently, that the thalamus is the pacemaker of thalamocortical synchronized activity in physiological in vitro conditions.