Serotonin (5-HT)-containing neurons in the dorsal raphe (DR) nucleus project throughout the forebrain and are implicated in many physiological processes and neuropsychiatric disorders. Diversity among these neurons has been characterized in terms of their neurochemistry and anatomical organization, but a clear sense of whether these attributes align with specific brain functions or terminal fields is lacking. DR 5-HT neurons can co-express additional neuroactive substances, increasing the potential for individualized regulation of target circuits. The goal of this study was to link DR neurons to a specific functional role by characterizing cells according to both their neurotransmitter expression and efferent connectivity; specifically, cells projecting to the medial prefrontal cortex (mPFC), a region implicated in cognition, emotion, and responses to stress. Following retrograde tracer injection, brainstem sections from Sprague-Dawley rats were immunohistochemically stained for markers of serotonin, glutamate, GABA, and nitric oxide (NO). 98% of the mPFC-projecting serotonergic neurons co-expressed the marker for glutamate, while the markers for NO and GABA were observed in 60% and less than 1% of those neurons, respectively. To identify potential target-specific differences in co-transmitter expression, we also characterized DR neurons projecting to a visual sensory structure, the lateral geniculate nucleus (LGN). The proportion of serotonergic neurons co-expressing NO was greater amongst cells targeting the mPFC vs LGN (60% vs 22%). The established role of 5-HT in affective disorders and the emerging role of NO in stress signaling suggest that the impact of 5-HT/NO co-localization in DR neurons that regulate mPFC circuit function may be clinically relevant. (C) 2017 Elsevier B.V. All rights reserved.
Neurochemical differences between target-specific populations of rat dorsal raphe projection neurons
Creators
Eric W. Prouty - Drexel University
Daniel J. Chandler - Drexel University
Barry D. Waterhouse - Drexel University
Publication Details
Brain research, v 1675, pp 28-40
Publisher
Elsevier
Number of pages
13
Grant note
R01 MH1011778 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
R01MH101178 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
Resource Type
Journal article
Language
English
Academic Unit
Neurobiology and Anatomy; [Retired Faculty]
Web of Science ID
WOS:000413608600004
Scopus ID
2-s2.0-85028929591
Other Identifier
991019168116504721
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