Intracellular Calcium and Control of Burst Generation in Neurons of Guinea‐Pig Neocortex in Vitro

Response properties of neurons in brain slices of guinea pig parietal neocortex were examined following intracellular injection of the Ca²⁺ chelators, EGTA and BAPTA. Although chelator injection did not cause any consistent change in passive membrane properties, it did induce 81% of neurons encountered at all sub‐pial depths to become ‘bursters’, in that just‐threshold depolarizing current pulses triggered all‐or‐none bursts of 2–5 fast action potentials. Transition to ‘burstiness’ was associated with disappearance of an AHP and appearance of a DAP. Although chelator caused a slight increase in steady‐state firing rate, marked accommodation persisted. Extracellular Co²⁺ or Mn²⁺ had an effect on steady‐state firing rate similar to that of the intracellular chelators; however, exposure to these Ca²⁺ channel blockers also caused steady state depolarization, increased resting input resistance and time constant, and profound spike broadening. This treatment never induced transition to ‘burstiness’. Chelator‐injected neurons ceased to generate bursts when Ca²⁺ was replaced by Mn²⁺ in the Ringer's solution. During exposure to 10⁻⁶ M TTX and 20 mM TEA, 50–200 msec Ca²⁺ spikes followed brief depolarizing pulses. As chelator was injected into the cell, there was progressive prolongation of the Ca²⁺ plateaus, which was associated with slowing of the rate at which membrane resistance gradually recovered following the initial increase in conductance. These findings indicate that under normal conditions, activity‐related increases in intracellular Ca²⁺ activate processes which prevent most neocortical neurons from being bursters. These processes probably include Ca²⁺ ‐dependent K⁺ currents, and Ca²⁺ ‐dependent Ca²⁺ channel inactivation.