SYNAPTIC REGULATION OF ACTION-POTENTIAL TIMING IN NEOSTRIATAL CHOLINERGIC INTERNEURONS

Action potentials in neostriatal cholinergic interneurons recorded in vivo are triggered by summation of two or three discrete synaptic depo larizations (Wilson at al., 1990). The ability and precision with whic h EPSPs and cPSPs regulate action potential timing was therefore inves tigated in vitro. Cholinergic interneurons were identified on the basi s of morphological and electrophysiological characteristics in neostri atal slices taken from 2- to 3-week-old postnatal rats recorded at 24- 26 degrees C. During periods of induced regular firing, intrastriatal stimuli were used to evoke pharmacologically isolated monosynaptic AMP A receptor-mediated EPSPs or GABA(A) receptor-mediated IPSPs. EPSPs ev oked during the interspike interval (ISI) produced a phase-dependent d ecrease in the ISI, whereas cPSPs produced a phase-independent prolong ation of the ISI. Injection of brief depolarizing currents mimicked th e action of EPSPs and revealed an alteration in the input resistance d uring the ISI. In contrast to cPSPs, the ability of brief hyperpolariz ing current injections to delay spike generation was phase-dependent. After blockade of GABAergic and glutamatergic synaptic transmission, s timuli failed to produce a detectable conductance change but could sti ll prolong the subsequent ISI primarily through a D1 dopamine receptor -mediated enhancement of the afterhyperpolarization (AHP). Hence, EPSP s are ideally suited to provide a precise regulation of spike timing i n cholinergic cells, whereas IPSPs are more likely to influence the ov erall level of excitability. The D1-mediated modulation of the AHP may contribute to the prolonged ISI seen in tonically active neurons in v ivo in monkeys trained to respond to a sensory cue.