Cellular profile of the dorsal raphe lateral wing sub-region: Relationship to the lateral dorsal tegmental nucleus

Abstract

As one of the main serotonergic (5HT) projections to the forebrain, the dorsal raphe nucleus (DRN) has been implicated in disorders of anxiety and depression. Although the nucleus contains the densest population of 5HT neurons in the brain, at least 50% of cells within this structure are non-serotonergic, including a large population of nitric oxide synthase (NOS) containing neurons. The DRN has a unique topographical efferent organization and can also be divided into sub-regions based on rostro-caudal and medio-lateral dimensions. NOS is co-localized with 5HT in the midline DRN but NOS-positive cells in the lateral wing (LW) of the nucleus do not express 5HT. Interestingly, the NOS LW neuronal population is immediately rostral to and in line with the cholinergic lateral dorsal tegmental nucleus (LDT). We used immunohistochemical methods to investigate the potential serotonergic regulation of NOS LW neurons and also the association of this cell grouping to the LDT. Our results indicate that >75% of NOS LW neurons express the inhibitory 5HT1A receptor and are cholinergic (> 90%). The findings suggest this assembly of cells is a rostral extension of the LDT, one that it is subject to regulation by 5HT release. As such the present study suggests a link between 5HT signaling, activation of cholinergic/NOS neurons, and the stress response including the pathophysiology underlying anxiety and depression.

Ethanol consumption in the Sprague–Dawley rat increases sensitivity of the dorsal raphe nucleus to 5,7-dihydroxytryptamine

“…Images were converted to 8-bit grayscale and inverted for comparison using CorelDraw Graphics Suite X6 Version 16.4.1.1281 (Corel Corporation, Ottawa, Canada). A sample of rats was selected for TPH2 quantification (n = 12 rats total, 3 per treatment group; Commons et al, 2003; Okere and Waterhouse, 2006; Vasudeva and Waterhouse, 2014). Positively stained cells were counted across 9 DRN sub-regions per animal according to Vasudeva and Waterhouse (2014).…”

0075 Nitrergic Neurons of the Dorsal Raphe Nucleus Encode Information About Stress Duration

“…While in some brain regions, NADPH-d activity is not exclusively due to the neuronal NOS isoform such as the dlPAG, in the DRN it has been verified that NADPH-d is only found in nNOS containing cells [4,12,21,23]. It has also been demonstrated that cellular intensity of NADPH-d is subject to experimental manipulation and the amount of formazan blue produced is a reflection of NOS activity at the time of fixation [4,12].…”

“…It has also been demonstrated that cellular intensity of NADPH-d is subject to experimental manipulation and the amount of formazan blue produced is a reflection of NOS activity at the time of fixation [4,12]. Changes in fixation and tissue processing parameters may cause variations in immunohistochemical association of NADPH-d intensity with NOS the experimental and control animals were simultaneously processed under identical conditions throughout restraint handling, isoflurane exposure, and tissue preparation to reduce inter-staining bias to the minimum.…”

“…Most of the neurons in the dorsomedial and ventromedial DRN, collectively known as the midline, display both NOS and tryptophan hydroxylase (TPH), but neurons in the caudal lateral wing (CLW) display either NOS or TPH exclusively [2,3]. Interestingly, more than 75% of the neurons in the CLW that contain NOS were also positive for inhibitory 5-HT 1A receptors, suggesting that those neurons are regulated by 5-HT [1,3,4]. Furthermore, it has been revealed that NOS neurons in the CLW also co-localize with cholinergic neurons making them a unique subset of neurons in the DRN [4].…”

“…Interestingly, more than 75% of the neurons in the CLW that contain NOS were also positive for inhibitory 5-HT 1A receptors, suggesting that those neurons are regulated by 5-HT [1,3,4]. Furthermore, it has been revealed that NOS neurons in the CLW also co-localize with cholinergic neurons making them a unique subset of neurons in the DRN [4]. The organization of a1111111111 a1111111111 a1111111111 a1111111111 a1111111111…”