Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain

Abstract

Serotonin neurons play a major role in many normal and pathological brain functions. In the rat these neurons have a varying number of cotransmitters, including neuropeptides. Here we studied, with histochemical techniques, the relation between serotonin, some other small-molecule transmitters, and a number of neuropeptides in the dorsal raphe nucleus (DRN) and the adjacent ventral periaqueductal gray (vPAG) of mouse, an important question being to establish possible differences from rat. Even if similarly distributed, the serotonin neurons in mouse lacked the extensive coexpression of nitric oxide synthase and galanin seen in rat. Although partly overlapping in the vPAG, no evidence was obtained for the coexistence of serotonin with dopamine, substance P, cholecystokinin, enkephalin, somatostatin, neurotensin, dynorphin, thyrotropin-releasing hormone, or corticotropin-releasing hormone. However, some serotonin neurons expressed the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD). Work in other laboratories suggests that, as in rat, serotonin neurons in the mouse midline DRN express the vesicular glutamate transporter 3, presumably releasing glutamate. Our study also shows that many of the neuropeptides studied (substance P, galanin, neurotensin, dynorphin, and corticotropin-releasing factor) are present in nerve terminal networks of varying densities close to the serotonin neurons, and therefore may directly or indirectly influence these cells. The apparently low numbers of coexisting messengers in mouse serotonin neurons, compared to rat, indicate considerable species differences with regard to the chemical neuronatomy of the DRN. Thus, extrapolation of DRN physiology, and possibly pathology, from rat to mouse, and even human, should be made with caution.

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

“…However, studies on mice with genetically deleted Galr1 (Galr1-KO) showed no effect in the tail suspension test, pharmacological manipulations did not alter the depression profile (65), and such mice showed increased anxiety-like behavior in the elevated plus-maze (66). It should be noted that the 5-HT neurons in the mouse DR, in contrast to the rat DR, do not express galanin (67)(68)(69)(70) and that the KO mice, of course, lack this receptor throughout life and in all parts of the brain (body).…”

“…In the rat, many of the 5-HT neurons express galanin (20,(22)(23)(24). However, a large number of nonserotonin cells exist in the rodent DR, with different electrophysiological characteristics (105)(106)(107) and neurotransmitter phenotypes, including GABA-, glutamate-, and peptidergic neurons, constituting some 50-70% of all DR neurons (70,(108)(109)(110)(111)(112)(113)(114).…”

“…GALR1 in the vPAG could be expressed in GABA interneurons, which are known to inhibit 5-HT neurons directly (116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127). Moreover, some 5-HT neurons in the rat and mouse lateral wings are GABA/GAD + (70,117,(128)(129)(130)(131), and thus probably corelease GABA and 5-HT. More recent studies report that of the ascending 5-HT neurons (132)(133)(134), 16% are GABAergic and project to the medial prefrontal cortex (135), as also suggested by electrophysiological studies (136).…”

The role of serotonin in adult hippocampal neurogenesis

“…The neuromodulator character of serotonin affects excitatory or inhibitory release mediated by glutamate or GABA (Schmitz et al, 1995, Li et al, 2000 with one study showing that serotonergic neurons itself can express the GABA-synthesizing enzyme glutamic acid decarboxylase (Fu et al, 2010). Furthermore, two-thirds of dorsal raphe Pet1 neurons exhibit vesicular glutamate transporter 3 that is required for glutamate release (Hioki et al, 2010, Liu et al, 2014.…”

Distinct Neurochemical and Functional Properties of GAD67-Containing 5-HT Neurons in the Rat Dorsal Raphe Nucleus

“…Of these, GABAergic and 5-HTergic transmissions can negatively regulate 5-HT release (Gallager and Aghajanian, 1976;Piñeyro and Blier, 1999), and are thereby considered possible targets of therapeutic interventions. Interestingly, some 5-HTergic neurons have been shown to express GABA or its synthetic enzyme glutamic acid decarboxylase (GAD) (Nanopoulos et al, 1982;Belin et al, 1983;Fu et al, 2010;Hioki et al, 2010), suggesting a possible corelease of 5-HT and GABA. In this regard, these neurons may have a unique mechanism that controls their firing activity through autoregulatory feedback inhibition.…”