Antidromic activation of dorsal raphe neurons from neostriatum: physiological characterization and effects of terminal autoreceptor activation.

Three types of neurons, distinguished on the basis of their spontaneous firing rates and patterns, extracellularly recorded waveforms and responses to neostriatal stimulation, were observed in the dorsal raphe nucleus in urethane-anesthetized rats. Type 1 neurons (presumed to be serotonergic) fired spontaneously from 0.1 to 3 spikes/s in a regular pattern, with initial positive-going bi- or triphasic action potentials. Type 1 cells exhibited long-latency antidromic responses to neostriatal stimulation (mean +/- S.E.M. 24.9 +/- 0.3 ms) that sometimes occurred at discrete multiple latencies, and supernormal periods persisting up to 100 ms following spontaneous spikes. Type 2 cells fired spontaneously in an irregular, somewhat bursty pattern from 0 to 2 spikes/s with initial negative-going biphasic spikes, and were antidromically activated from neostriatal stimulation at shorter latencies than Type 1 cells (21.8 +/- 0.9 ms). Type 3 cells were characterized by initial positive-going biphasic waveforms and displayed a higher discharge rate (5-30 spikes/s) than Type 1 or Type 2 cells. Type 3 cells could not be antidromically activated from neostriatal stimulation. The relatively long conduction time to neostriatum of the Type 1 presumed serotonergic neuron is discussed with respect to previous interpretations of the synaptic action of serotonin in the neostriatum. In conjunction with these antidromic activation studies, the neurophysiological consequences of serotonergic terminal autoreceptor activation were examined by measuring changes in the excitability of serotonergic terminal fields in the neostriatum following administration of the serotonin autoreceptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The excitability of serotonergic terminal fields was decreased by intravenous injection of 40 micrograms/kg 5-MeODMT, and by infusion of 10-50 microM 5-MeODMT directly into the neostriatum. These results are interpreted from the perspective of mechanisms underlying autoreceptor-mediated regulation of serotonin release.