Involvement of NMDA and GABA(A) receptors in modulation of spontaneous activity in hippocampal culture: Interrelations between burst firing and intracellular calcium signal.

Spontaneous burst firing is a hallmark attributed to the neuronal network activity. It is known to be accompanied by intracellular calcium [Са 2+ ] i oscillations within the bursting neurons. Studying mechanisms underlying regulation of burst firing is highly relevant, since impairment in neuronal bursting accompanies different neurological disorders. In the present study, the contribution of NMDA and GABA(A) receptors to the shape formation of spontaneous burst -was studied in cultured hippocampal neurons. A combination of inhibitory analysis with simultaneous registration of neuronal bursting by whole-cell patch clamp and calcium imaging was used to assess spontaneous burst firing and [Са 2+ ] i level. Using bicuculline and D-AP5 we showed that GABA(A) and NMDA receptors effectively modulate burst plateau phase and [Са 2+ ] i transient spike which can further affect action potential (AP) amplitudes and firing frequency within a burst. Bicuculline significantly elevated the amplitude and reduced the duration of both burst plateau phase and [Са 2+ ] i spike resulting in an increase of AP firing frequency and shortening of AP amplitudes within a burst. D-AP5 significantly decreases the amplitude of both plateau phase and [Са 2+ ] i spike along with a burst duration that correlated with an increase in AP amplitudes and reduced firing frequency within a burst. The effect of bicuculline was occluded by co-addition of D-AP5 revealing modulatory role of GABA(A) receptors to the NMDA receptor-mediated formation of the burst. Our results provide new evidence on importance of NMDA and GABA(A) receptors in shaping burst firing and Ca 2+ transient spikes in cultured hippocampal neurons. • GABA(A)R and NMDAR bi-directionally modulate burst plateau phase amplitude. • GABA(A)R and NMDAR bi-directionally modulate burst Ca2+-spike amplitude. • GABA(A)R and NMDAR modulate burst APs amplitude and firing frequency. • NMDAR plays leading role in tuning parameters of the burst. • GABA(A)R modulates NMDAR-mediated tuning of the burst.