Topographic organization and neurochemical identity of dorsal raphe neurons that project to the trigeminal somatosensory pathway in the rat

Abstract

The primary goals of this study were to: 1) examine the distribution of neurons within the dorsal raphe (DR) nucleus that project to cortical and subcortical sites along the trigeminal somatosensory pathway in rat; 2) determine the extent to which different regions within this ascending sensory system receive collateral projections from the same DR neuron; and 3) identify the putative transmitters contained within these DR projection neurons. Long-Evans hooded rats received pressure injections of various combinations of retrograde fluorescent tracers; into the whisker-related regions of the primary somatosensory cortex (barrel field cortex [BC]), ventral posterior medial thalamus (VPM), and principal nucleus of the trigeminal complex (PrV). The distribution of retrogradely labeled neurons within the DR was examined by fluorescence microscopy. The major finding was that cortically projecting neurons were located within the midline regions of the rostral portion of the DR, whereas cells projecting to subcortical trigeminal somatosensory structures were distributed bilaterally in the lateral wing regions of the DR as well as in the midline portions of the nucleus. Single neurons that send axon collaterals to multiple cortical and subcortical trigeminal somatosensory targets were observed in the dorsomedian and ventromedian regions of the DR. DR neurons that projected to cortical and subcortical sites contained serotonin but not tyrosine hydroxylase, the marker enzyme for catecholamine transmitters. Taken together, these findings provide further evidence of neurochemical specificity and functional anatomical organization within the DR efferent projection system.

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

“…It is noteworthy that the terminal innervation of the basal forebrain and extended amygdala was located primarily on the side ipsilateral to the injection site. Retrograde tracing studies have demonstrated that the majority of serotonergic DRN neurons projecting to caudate-putamen (Van der Kooy, 1979), neocortex (O'Hearn and Molliver, 1984), prefrontal cortex and nucleus accumbens (Van Bockstaele et al, 1993), and components of the trigeminal somatosensory pathway (Kirifides et al, 2001) are located ipsilateral to the tracer injection site. The present anterograde tracing data indicate that the nonserotonergic projection from the DRN to the basal forebrain and the extended amygdala also originates primarily from the ipsilateral DRN.…”

“…Experiments combining retrograde tracing with serotonin (5-HT) immunostaining have established that many nonserotonergic DRN neurons project extrinsically (Beitz et al, 1986;Ma et al, 1991;Petrov et al, 1992Petrov et al, , 1994 Van Bockstaele et al, 1993;Kirifides et al, 2001;Kim et al, 2004;Halberstadt and Balaban, 2006a). Nonserotonergic DRN projections are neurochemically heterogeneous, and may contain a number of transmitter substances, including glutamate (Schwarz and Schwarz, 1992;Kiss et al, 2002), dopamine (Pohle et al, 1984;Descarries et al, 1986;Yoshida et al, 1989;Stratford and Wirtshafter, 1990;Hasue and Shammah-Lagnado, 2002), GABA (Nanopoulos et al, 1982;Stamp and Semba, 1995;Ford et al, 1995;Jankowski and Sesack, 2002), nitric oxide (Xu and Hokfelt, 1997;Simpson et al, 2003), and neuropeptides such as vasoactive intestinal polypeptide (VIP) (Petit et al, 1995;Kozicz et al, 1998) and cholecystokinin Seroogy and Fallon, 1989).…”

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

“…A disadvantage of this type of manipulation is that it would likely have relatively global effects, since these dorsal raphe neurons innervate extensive regions of the brain, including regions that are known to project to the IC (for example, cochlear nucleus: Zook and Casseday 1985,Oliver 1987,Vater and Feng 1990Klepper and Herbert 1991;amygdala: Marsh et al 2002,Jacobs et al 1978. Indeed, even single serotonergic neurons may send collaterals to different nuclei along ascending sensory pathways (Kirifides et al 2001). Thus, stimulating the dorsal raphe nucleus would likely alter the response properties of inputs to the IC as well as those of neurons within the IC itself.…”

MDMA (3,4-Methylenedioxymethamphetamine)-Mediated Distortion of Somatosensory Signal Transmission and Neurotransmitter Efflux in the Ventral Posterior Medial Thalamus

“…This system transmits tactile information from the facial whiskers of rat to the contralateral somatosensory cortex via the brainstem trigeminal nucleus of V and the ventral posterior medial thalamus (VPM). All regions in this network receive serotonergic and noradrenergic projections and, thus, are vulnerable to the pharmacological effects of MDMA (Simpson et al, 1997;Kirifides et al, 2001).…”