Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat

Abstract

As well recognized, serotonergic (5-HT) fibers distribute widely throughout the forebrain, including the amygdala. Although a few reports have examined the 5-HT innervation of select nuclei of the amygdala in the rat, no previous report has described overall 5-HT projections to the amygdala in the rat. Using immunostaining for the serotonin transporter, SERT, we describe the complete pattern of distribution of 5-HT fibers to the amygdala (proper) and to the extended amygdala in the rat. Based on its ontogenetic origins, the amygdalar was subdivided into two major parts: pallial and subpallial components, with the pallial component further divided into superficial and deep nuclei (Olucha-Bordonau et al., 2015). SERT+ fibers were shown to distribute moderately to densely to the deep and cortical pallial nuclei, but, by contrast, lightly to the subpallial nuclei. Specifically, (1) of the deep pallial nuclei, the lateral, basolateral and basomedial nuclei contained a very dense concentration of 5-HT fibers; (2) of the cortical pallial nuclei, the anterior cortical and amygdala-cortical transition zone, rostrally, and the posteromedial and posterolateral nuclei, caudally, contained a moderate concentration of 5-HT fibers; and (3) of the subpallial nuclei, the anterior nuclei and the rostral part of the medial (Me) nuclei contained a moderate concentration of 5-HT fibers, whereas caudal regions of Me as well as the central nuclei and the intercalated nuclei contained a sparse/light concentration of 5-HT fibers. Regarding the extended amygdala (primarily the bed nucleus of stria terminalis, BST), on the whole, the BST contained moderate numbers of 5-HT fibers, spread fairly uniformly throughout BST. The findings were discussed with respect to a critical serotonergic influence on the amygdala, particularly on the basal complex, and extended amygdala in the control of states of fear and anxiety.

Integrated single-cell atlases unveil the operation principles of whole-brain 5-HT neuronal subsystems

“…Notably, the three SR subpopulations showed substantial innervation of the telencephalon (including pallium and subpallium). This is consistent with previous findings that 5-HT neurons in the raphe nucleus intensively project to forebrain regions including prefrontal cortex, amygdala, and dorsal hippocampus in mammals ( 26 , 36 , 37 ). The three SR subpopulations display distinct projection patterns.…”

Integrated single-cell atlases unveil the operation principles of whole-brain 5-HT neuronal subsystems

“…Notably, the three SR subpopulations showed substantial innervation of the telencephalon (including pallium and subpallium). This is consistent with previous findings that 5-HT neurons in the raphe nucleus intensively project to forebrain regions including prefrontal cortex, amygdala, and dorsal hippocampus in mammals ( 26 , 36 , 37 ). The three SR subpopulations display distinct projection patterns.…”

Serotonin 2C receptors in the basolateral amygdala mediate the anxiogenic effect caused by serotonergic activation of the dorsal raphe dorsomedial subnucleus

“…The most important of the current findings however, is that the anxiogenic effect caused by intra-DRD injection of WAY-100635 in both tests was blocked by previous administration of SB-242084 in the BLA, fully implicating 5-HT2C receptors in the mediation of this response. This result is consonant with neuroanatomical evidence showing that most of the DR inputs to the BLA are serotonergic, with the highest percentage of these projecting neurons departing from the DRD, DRC, and DRV (Fernandez et al, 2015; Hale et al, 2008; Linley et al, 2016; Muzerelle et al, 2016). Moreover, stimulation of 5-HT neurons by local administration of either urocortin 2, a preferential CRF-2 receptor agonist, or kainic acid in the central area of the DR, in a region encompassing the DRD and DRV, increases serotonin release in the BLA, as shown by in vivo microdialysis (Amat et al, 2004; Viana et al, 1997).…”

Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala

“…Elevated GABA signaling in the CeA is considered a hallmark of alcohol dependence across species (Roberto et al, 2004;Augier et al, 2018;Jimenez et al, 2019). Importantly, the CeA and the DRN are reciprocally connected (Vertes, 1991;Linley et al, 2016), and there is compelling evidence for heightened DRN activity following chronic alcohol exposure in mice (Lowery-Gionta et al, 2015). Thus, given dense expression of 5-HT receptors in the CeA (Asan et al, 2013), we here examined potential neuroadaptations of CeA 5-HT signaling induced by alcohol dependence and withdrawal using ex vivo slice electrophysiology and ISH.…”

Integrated single-cell atlases unveil the operation principles of whole-brain 5-HT neuronal subsystems

“…Notably, the three SR subpopulations showed substantial innervation of the telencephalon (including pallium and subpallium). This is consistent with previous findings that 5-HT neurons in the raphe nucleus intensively project to forebrain regions including prefrontal cortex, amygdala, and dorsal hippocampus in mammals ( 26 , 36 , 37 ). The three SR subpopulations display distinct projection patterns.…”

Serotonin 2C receptors in the basolateral amygdala mediate the anxiogenic effect caused by serotonergic activation of the dorsal raphe dorsomedial subnucleus

“…The most important of the current findings however, is that the anxiogenic effect caused by intra-DRD injection of WAY-100635 in both tests was blocked by previous administration of SB-242084 in the BLA, fully implicating 5-HT2C receptors in the mediation of this response. This result is consonant with neuroanatomical evidence showing that most of the DR inputs to the BLA are serotonergic, with the highest percentage of these projecting neurons departing from the DRD, DRC, and DRV (Fernandez et al, 2015; Hale et al, 2008; Linley et al, 2016; Muzerelle et al, 2016). Moreover, stimulation of 5-HT neurons by local administration of either urocortin 2, a preferential CRF-2 receptor agonist, or kainic acid in the central area of the DR, in a region encompassing the DRD and DRV, increases serotonin release in the BLA, as shown by in vivo microdialysis (Amat et al, 2004; Viana et al, 1997).…”

Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala

“…Elevated GABA signaling in the CeA is considered a hallmark of alcohol dependence across species (Roberto et al, 2004;Augier et al, 2018;Jimenez et al, 2019). Importantly, the CeA and the DRN are reciprocally connected (Vertes, 1991;Linley et al, 2016), and there is compelling evidence for heightened DRN activity following chronic alcohol exposure in mice (Lowery-Gionta et al, 2015). Thus, given dense expression of 5-HT receptors in the CeA (Asan et al, 2013), we here examined potential neuroadaptations of CeA 5-HT signaling induced by alcohol dependence and withdrawal using ex vivo slice electrophysiology and ISH.…”

Integrated single-cell atlases unveil the operation principles of whole-brain 5-HT neuronal subsystems

“…Notably, the three SR subpopulations showed substantial innervation of the telencephalon (including pallium and subpallium). This is consistent with previous findings that 5-HT neurons in the raphe nucleus intensively project to forebrain regions including prefrontal cortex, amygdala, and dorsal hippocampus in mammals ( 26 , 36 , 37 ). The three SR subpopulations display distinct projection patterns.…”

Serotonin 2C receptors in the basolateral amygdala mediate the anxiogenic effect caused by serotonergic activation of the dorsal raphe dorsomedial subnucleus

“…The most important of the current findings however, is that the anxiogenic effect caused by intra-DRD injection of WAY-100635 in both tests was blocked by previous administration of SB-242084 in the BLA, fully implicating 5-HT2C receptors in the mediation of this response. This result is consonant with neuroanatomical evidence showing that most of the DR inputs to the BLA are serotonergic, with the highest percentage of these projecting neurons departing from the DRD, DRC, and DRV (Fernandez et al, 2015; Hale et al, 2008; Linley et al, 2016; Muzerelle et al, 2016). Moreover, stimulation of 5-HT neurons by local administration of either urocortin 2, a preferential CRF-2 receptor agonist, or kainic acid in the central area of the DR, in a region encompassing the DRD and DRV, increases serotonin release in the BLA, as shown by in vivo microdialysis (Amat et al, 2004; Viana et al, 1997).…”

Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala

“…Elevated GABA signaling in the CeA is considered a hallmark of alcohol dependence across species (Roberto et al, 2004;Augier et al, 2018;Jimenez et al, 2019). Importantly, the CeA and the DRN are reciprocally connected (Vertes, 1991;Linley et al, 2016), and there is compelling evidence for heightened DRN activity following chronic alcohol exposure in mice (Lowery-Gionta et al, 2015). Thus, given dense expression of 5-HT receptors in the CeA (Asan et al, 2013), we here examined potential neuroadaptations of CeA 5-HT signaling induced by alcohol dependence and withdrawal using ex vivo slice electrophysiology and ISH.…”