Page 1 SEROTONERGIC AND NON-SEROTONERGIC DORSAL RAPHE NEURONS ARE PHARMACOLOGICALLY AND ELECTROPHYSIOLOGICALLY HETEROGENEOUS

The dorsal raphe nucleus (DRN) projects serotonergic axons throughout the brain and is involved in a variety of physiological functions. However, it also includes a large population of cells that contain other neurotransmitters. To clarify the physiological and pharmacological differences between the serotonergic and non-serotonergic neurons of the DRN, their postsynaptic responses to 5hydroxytryptamine (5-HT, serotonin), to selective activation of 5-HT1A or 5-HT2A/C receptors and their action potential characteristics were determined using in vitro patch clamp recordings. The slices containing these neurons were then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic neurons. It was found that subpopulations of both serotonergic and non-serotonergic neurons (1) responded to 5-HT with outward (i.e. inhibitory) and inward (i.e. excitatory) currents, (2) responded to both 5-HT1A and 5-HT2A/C receptor activation with outward and inward currents, respectively, and (3) displayed overlapping action potential characteristics. These findings suggest that serotonergic and non-serotonergic neurons in the DRN are both heterogeneous with respect to their individual pharmacological and electrophysiological characteristics. The findings also suggest that the activity of the different populations of DRN neurons will display heterogeneous changes when the serotonergic tone in the DRN is altered by neurological disorders, or by drug treatment.