MECHANISM OF SYNCHRONIZED CA2-NEURONS( OSCILLATIONS IN CORTICAL)

Dissociated rat cortical neurons reassociate in vitro to form synaptic ally connected networks. Removal of Mg2+ from the extracellular medium then induces neurons in the network to undergo synchronized oscillati ons of cytoplasmic calcium. Previous studies have shown that these cal cium oscillations involve the activation of NMDA receptors and that th e rising phase of each calcium spike is coincident with a brief burst of action potentials (Robinson et al., Jpn. J. Physiol. 43 (Suppl. 1) (1993) S125-130; Robinson et al., J. Neurophysiol. 70 (1993) 1606-1616 ; Murphy et al., J. Neurosci. 12 (1992) 4834-4845). We have found that these calcium oscillations are dependent on an influx of extracellula r calcium but are independent of mobilization of calcium from intracel lular stores. The influx of extracellular Ca2+ occurs primarily throug h L-type voltage-gated calcium channels (VGCCs), since diltiazem inhib its calcium oscillations under all conditions. On the other hand, N-, P/Q-, and T-type VGCCs are not required for calcium oscillations, alth ough inhibitors of these channels may act as partial antagonists. In a ddition to removal of Mg2+, oscillations can also be induced by the in hibition of voltage-gated K+ channels with 4-aminopyridine (4-AP), a t reatment known to increase neurotransmitter release. In the presence o f 4-AP, synchronized calcium oscillations become independent of NMDA r eceptor activation, although they continue to require activation of AM PA/KA receptors. A model for the mechanism of neuronal calcium oscilla tions and the reason for their synchrony is presented. (C) 1997 Elsevi er Science B.V.