Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex

doi:10.1016/0006-8993(86)91332-6

Brain Research

Volume 382, Issue 2, 24 September 1986, Pages 213-238

https://doi.org/10.1016/0006-8993(86)91332-6 Get rights and content

Abstract

Using cobalt-enhanced immunohistochemistry, the tracing of retrograde transport of horseradish peroxidase (HRP) and experimental manipulations, a widespread localization of corticotropin-releasing factor-like immunoreactive (CRFI) structures in the rat amygdaloid complex, and CRFI-containing pathways from the amygdala to the lower brainstem, bed nucleus of the stria terminalis (bst) and ventromedial nucleus of the hypothalamus (VMH) have been demonstrated. By means of cobalt-enhanced immunohistochemistry, CRFI cells were detected in almost all the regions of the amygdala, including the central amygdaloid nucleus (Ce), basolateral amygdaloid nucleus (Bl), intra-amygdaliod bed nucleus of the stria terminalis (Abst), medial amygdaloid nucleus (Me), amygdalohippocampal area (Ahi), posterior cortical amygdaloid nucleus (Aco), lateral amygdaloid nucleus (La), anterior amygdaloid area (AAA) and basomedial amygdaloid nucleus (Bm). Neural processes with CRFI were found in all of the above areas. The greatest density of CRFI fibres was observed in the Ce, the Me and Ahi. Unilateral lesions located in the Ce and adjacent areas caused in ipsilateral decrease in CRFI fibre number in the lateral hypothalamic area (LH), mesencephalic reticular formation (RF), dorsal (Dpb) and ventral (Vpb) parabrachial nuclei, mesencephalic nucleus of the trigeminal nerve (MeV) and in the lateral division of the bst (bstl). In addition, ipsilateral CRFI fibres decreasen in number in the core and shell of the VMH after unilateral lesions of the corticomedial amygdala (CoM) and ventral subiculum (S). These findings suggest that (1) the CRFI cells in the Ce and adjacent areas innervate the Dpb, Vpb and MeV through the LH and RF; (2) the CRFI fibres in the bstl are supplied by the Ce and adjacent areas; and (3) the CoM and S give rise to the CRFI fibres to the VMH. The distribution of retrogradely transported HRP has confirmed these projections. Furthermore, combined HRP and immunohistochemical staining has demonstrated double labeled cells in the Ce following HRP injection into the Dpb, Vpb, MeV and bstl. This provides direct evidence for the amygdalofugal CRF-containing projections to the lower brainstem and bstl. Double-labeled cells were not seen in the CoM and S after HRP injection into the VMH.

References (120)

Y. Ben-Ari et al.
Regional distribution of choline acetyltransferase and acetylcholinesterase within the amygdaloid complex and stria terminalis system
Brain Research
(1977)
C. Bennett-Clarke et al.
Distribution of somatostatin in the rat brain: telencephalon and diencephalon
Brain Research
(1980)
M.R. Brown et al.
Comparison of the biologic actions of corticotropin releasing factor and sauvagine
Regul. Peptides
(1982)
P.C. Emson et al.
Contributions of different afferent pathways to the catecholamine and 5-hydroxytryptamine-innervation of the amygdala: a neurochemical and histochemical study
Neuroscience
(1979)
P.C. Emson et al.
Substance P in the amygdaloid complex, bed nucleus and stria terminalis of the rat brain
Brain Research
(1978)
D. Fellmann et al.
Immunocytochemical demonstration of corticoliberin-like immunoreactivity (CLI) in neurons of the rat amygdala central nucleus (ACN)
Neurosci. Lett.
(1982)
P. Gloor
Electrophysiological studies on the connections of the amygdaloid nucleus in the cat
Electroencephalogr. Clin. Neurophysiol.
(1955)
V.S. Harris et al.
Copulatory behaviour in male rats following amygdaloid lesions
Brain Research
(1975)
S. Inagaki et al.
Ontogeny of substance P-containing neuron system of the rat: immunohistochemical analysis. I. Forebrain and upper brain stem
Neuroscience
(1982)
K. Itoh et al.
Application of coupled oxidation reaction to electromicroscopic demonstration of horseradish peroxidase: cobalt-glucose oxidase method
Brain Research
(1979)

Y. Kawai et al.

Long descending projections from amygdaloid somatostatin-containing cells to the lower brainstem

Brain Research

(1982)

Y. Kawai et al.

Multiple innervation by substance P-containing fibres in the parabrachial area of the rat

Neurosci. Lett.

(1982)

Y. Kubota et al.

The distribution of cholecystokinin octapeptide-like structures in the lower brain stem of the rat: an immunohistochemical analysis

Neuroscience

(1983)

A. Ljungdahl et al.

Distribution of substance P-like immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals

Neuroscience

(1978)

P.G.M. Luiten et al.

The cortico-medial amygdala in the central nervous system organization of agonistic behaviour

Brain Research

(1985)

P.G.M. Luiten et al.

Interrelations between lateral, dorsomedial, and ventromedial hypothalamic nuclei in the rat, an HRP study

Brain Research

(1980)

L. Meliza et al.

Effect of anterior prepiriform and medial amygdaloid lesions on acquisition of taste-avoidance and response to dietary amino acid imbalance

Physiol. Behav.

(1981)

I. Merchenthaler

Corticotropin releasing factor (CRF)-like immunoreactivity in the rat central nervous system. Extrahypothalamic distribution

Peptides

(1984)

I. Merchenthaler et al.

The paraventriculo-infundibular corticotropin releasing factor (CRF)-pathways as revealed by immunohistochemistry in long term hypophysectomized or adrenalectomized rats

Regul. Peptides

(1983)

M.-M. Mesulam et al.

Differential sensitivity between blue and brown reaction procedures for HRP neurohistochemistry

Neurosci. Lett.

(1977)

H. Minagawa et al.

Ontogeny of neurotensin-containing neuron system of the rat: immunohistochemical analysis. II. Lower brainstem

Neuroscience

(1983)

J.E. Morley et al.

Corticotropin releasing factor, grooming and ingestive behaviour

Life Sci.

(1982)

R. Norgren

Projections from the nucleus of the solitary tract in the rat

Neuroscience

(1978)

J.A. Olschowka et al.

The distribution of corticotropin releasing factor-like immunoreactive neurons in rat brain

Peptides

(1982)

Y. Osumi et al.

Inhibition of gastric acid secretion and mucosal blood flow induced by intraventricularly applied neurotensin in rats

Life Sci.

(1978)

Y.S. Palka et al.

Obesity and increased growth following partial or complete isolation of ventromedial hypothalamus

Physiol. Behav.

(1971)

L.P. Renaud et al.

Amygdala afferents from the mediodorsal hypothalamus: an electrophysiological and neuroanatomical study in the rat

Brain Research

(1977)

G.W. Roberts et al.

Loss of immunoreactive VIP in the bed nucleus following lesions of the stria terminalis

Brain Research

(1980)

G.W. Roberts et al.

Distribution of neuropeptides in the limbic system of the rat: the amygdaloid complex

Neuroscience

(1982)

M. Sakanaka et al.

Experimental immunohistochemical studies on the amygdalofugal peptidergic (substance P and somatostatin) fibres in the stria terminalis of the rat

Brain Research

(1981)

C.B. Saper et al.

Efferent connections of the parabrachial nucleus in the rat

Brain Research

(1980)

P.E. Sawchenko et al.

A method for tracing biochemically defined pathways in the central nervous system using combined fluorescence retrograde transport and immunohistochemical techniques

Brain Research

(1981)

E.C. Azmitia et al.

An autoradiographic analysis of the different ascending projections of the dorsal and median raphe nuclei in the rat

J. Comp. Neurol.

(1978)

J.R. Baker

Cytological Technique

(1946)

L.L. Bernardi et al.

Effect of hypothalamic lesion at different loci on development of hyperinsulinemia and obesity in the weanling rat

J. Comp. Neurol.

(1971)

L.L. Bernardi et al.

Growth and obesity in male rat after placement of ventromedial hypothalamic lesion at four different ages

J. Endocrinol.

(1967)

D.R. Britton et al.

Intraventricular corticotropin releasing factor enhances behavioural effects of novelty

Life Sci.

(1982)

J.R. Brobeck

Mechanism of the development of obesity in animals with hypothalamic lesions

Physiol. Rev.

(1946)

M.R. Brown et al.

Corticotropin releasing factor: actions on the sympathetic nervous system and metabolism

Endocrinology

(1982)

J. Carlsen et al.

Cholinergic projections from the basal forebrain to the basolateral amygdaloid complex: a combined retrograde fluorescent and immunohistochemical study

J. Comp. Neurol.

(1985)

H.G. Carrer et al.

New facts concerning the role played by the ventromedial nucleus in control of estrus cycle duration and sexual receptivity in the rat

Neuroendocrinology

(1973/1974)

H.J. Cho et al.

Ontogeny of cholecystokinin-8-containing neuron system of the rat: an immunohistochemical analysis. I. Forebrain and upper brain stem

J. Comp. Neurol.

(1983)

W.M. Cowan et al.

The connections of the amygdala

J. Neurol. Neurosurg. Psychiat.

(1965)

A.C. Cuello et al.

The distribution of substance P immunoreactive fibres in the rat central nervous system

J. Comp. Neurol.

(1978)

M.A. Della-Fera et al.

Cholecystokinin octapeptide-containing picomole injections into the cerebral ventricles of sheep suppress feeding

Science

(1979)

M. Denavit-Saibié et al.

Descending input from the pneumotaxic system to the lateral respiratory nucleus of the medulla. An anatomical study with the horseradish peroxidase technique

Neurosci. Lett.

(1977)

J.S. de Olmos

The amygdaloid projection field in the rat as studied with the cupric-silver method

W. Eldred et al.

Comparison of fixation and penetration enhancement technique for use in ultrastructural immunocytochemistry

J. Histochem. Cytochem.

(1983)

J.H. Fallon et al.

Catecholamine innervation of the basal forebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex

J. Comp. Neurol.

(1978)

Cited by (318)

Distinct populations of corticotropin-releasing factor (CRF) neurons mediate divergent yet complementary defensive behaviors in response to a threat
2023, Neuropharmacology
Defensive behaviors in response to a threat are shared across the animal kingdom. Active (fleeing, sheltering) or passive (freezing, avoiding) defensive responses are adaptive and facilitate survival. Selecting appropriate defensive strategy depends on intensity, proximity, temporal threat threshold, and past experiences. Hypothalamic corticotropin-releasing factor (CRF) is a major driver of an acute stress response, whereas extrahypothalamic CRF mediates stress-related affective behaviors. In this review, we shift the focus from a monolithic role of CRF as an anxiogenic peptide to comprehensively dissecting contributions of distinct populations of CRF neurons in mediating defensive behaviors. Direct interrogation of CRF neurons of the central amygdala (CeA) or the bed nucleus of the stria terminalis (BNST) show they drive unconditioned defensive responses, such as vigilance and avoidance of open spaces. Although both populations also contribute to learned fear responses in familiar, threatening contexts, CeA-CRF neurons are particularly attuned to the ever-changing environment. Depending on threat intensities, they facilitate discrimination of salient stimuli predicting manageable threats, and prevent their generalization. Finally, hypothalamic CRF neurons mediate initial threat assessment and active defense such as escape to shelter. Overall, these three major populations of CRF neurons demonstrate divergent, yet complementary contributions to the versatile defense system: heightened vigilance, discriminating salient threats, and active escape, representing three legs of the defense tripod. Despite the ‘CRF exhaustion’ in the field of affective neuroscience, understanding contributions of specific CRF neurons during adaptive defensive behaviors is needed in order to understand the implications of their dysregulation in fear- and anxiety-related psychiatric disorders.
This article is part of the Special Issue on “Fear, Anxiety and PTSD”.
Aberrant functional connectivity of the bed nucleus of the stria terminalis and its age dependence in children and adolescents with social anxiety disorder
2023, Asian Journal of Psychiatry
Social anxiety disorder (SAD) is a prevalent and impairing mental disorder among children and adolescents. The bed nucleus of the stria terminalis (BNST) plays a critical role in anxiety disorders, including valence surveillance and hypervigilance for potential threats. However, the role of BNST and its related functional network in children and adolescents with SAD has not been fully investigated. This study examined the aberration of BNST’s functional connectivity and its age dependence in adolescents with SAD.
Using a sample of 75 SAD patients and 75 healthy controls (HCs) children aged 9–18 years old, we delineated the group-by-age interaction of BNST-seeded functional connectivity (FC) during resting state and movie-watching. The relationships between BNST-seeded FC and clinical scores were also examined.
During movie viewing, the FC between the right BNST and the left amygdala, bilateral posterior cingulate cortex (PCC), bilateral superior temporal cortex, and right pericalcarine cortex showed a diagnostic group-by-age interaction. Compared to HCs, SAD patients showed a significant enhancement of the above FC at younger ages. Meanwhile, they showed an age-dependent decrease in FC between the right BNST and left amygdala. Furthermore, for SAD patients, FC between the right BNST and left amygdala during movie viewing was positively correlated with separation anxiety scores.
The right BNST plays an essential role in the aberrant brain functioning in children and adolescents with SAD. The atypicality of BNST’s FC has remarkable age dependence in SAD, suggesting an association of SAD with neurodevelopmental traits.
Anatomical and molecular features of the amygdalohippocampal transition area and its role in social and emotional behavior processes
2022, Neuroscience and Biobehavioral Reviews
The amygdalohippocampal transition area (AHi) has emerged as a critical nucleus of sociosexual behaviors such as mating, parenting, and aggression. The AHi has been overlooked in rodent and human amygdala studies until recently. The AHi is hypothesized to play a role in metabolic and cognitive functions as well as social behaviors based on its connectivity and molecular composition. The AHi is small nucleus rich in neuropeptide and hormone receptors and is contiguous with the ventral subiculum of the hippocampus—hence its designation as a “transition area”. Literature focused on the AHi can be difficult to interpret because of changing nomenclature and conflation with neighboring nuclei. Here we summarize what is currently known about AHi structure and development, connections throughout the brain, molecular composition, and functional significance. We aim to delineate current knowledge regarding the AHi, identify potential functions with supporting evidence, and ultimately make clear the importance of the AHi in sociosexual function.
Extended amygdala, conditioned withdrawal and memory consolidation
2022, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Opioid withdrawal can be associated to environmental cues through classical conditioning. Exposure to these cues can precipitate a state of conditioned withdrawal in abstinent subjects, and there are suggestions that conditioned withdrawal can perpetuate the addiction cycle in part by promoting the storage of memories. This review discusses evidence supporting the hypothesis that conditioned withdrawal facilitates memory consolidation by activating a neurocircuitry that involves the extended amygdala. Specifically, the central amygdala, the bed nucleus of the stria terminalis, and the nucleus accumbens shell interact functionally during withdrawal, mediate expression of conditioned responses, and are implicated in memory consolidation. From this perspective, the extended amygdala could be a neural pathway by which drug-seeking behaviour performed during a state of conditioned withdrawal is more likely to become habitual and persistent.
Bed Nucleus of Stria Terminalis (BNST) circuits
2022, Neurocircuitry of Addiction
The bed nucleus of the stria terminalis (BNST) is a limbic forebrain structure nestled below the lateral ventricles, surrounding the anterior commissure, and its neighboring regions, the striatum, thalamus, and hypothalamus. The BNST is an integral component of the extended amygdala, a network of brain areas that span the anterior/posterior gradient of the brain starting anterior in the nucleus accumbens, continuing through the transition areas, and into the BNST and the central nucleus of the amygdala. The BNST has functional outputs relevant for reward and stress, and it is interconnected with brain areas involved in generating and regulating mood and overall emotional state. Various brain circuits are regulated by BNST outputs, and complex intrinsic microcircuits regulate the overall activity state of the BNST and modulate outputs to other brain areas. The BNST integrates cortical and subcortical inputs to determine affective state and whether a stimulus/situation will produce fear, anxiety, depression, irritability, or reward motivation/goal-directed behavior. On the cellular level, this highly heterogeneous brain area contains a diverse population of cell types and inputs, thus allowing for nuanced regulation of emotional state and behavioral responses.
Sex differences in pain-induced modulation of corticotropin-releasing hormone neurons in the dorsolateral part of the stria terminalis in mice
2021, Brain Research
We earlier reported female-biased, sex-specific involvement of the dorsolateral bed nucleus of the stria terminalis (dl BST) in the formalin-induced pain response in rats. The present study investigated pain effects on mice behaviors. Because the dl BST is densely populated with corticotropin-releasing hormone (CRH) neurons, we examined sex differences in these parameters for the dl BST CRH neurons in male and female mice of a mouse line for which the CRH gene promoter (corticotropin-releasing factor [CRF]-Venus ΔNeo) controls the expression of the modified yellow fluorescent protein (Venus).
Approximately 92% of Venus-positive cells in the dl BST were also CRH mRNA-positive, irrespective of sex. Therefore, the cells identified using Venus fluorescence were regarded as CRH neurons. A female-biased sex difference was observed in pain-induced behaviors during the interphase (5–15 min after formalin injection) but not during the later phase (phase 2, 15–60 min) in wild-type mice. In CRF-Venus ΔNeo mice, a female-biased difference was observed in either the earlier phase (phase 1, 0–5 min) or the interphase, but not in phase 2. Patch-clamp recordings taken using an acute BST slice obtained from a CRF-Venus ΔNeo mouse after formalin injection showed miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). Remarkably, the mEPSCs frequency was higher in the Venus-expressing cells of formalin-injected female mice than in vehicle-treated female mice. Male mice showed no increase in mEPSC frequency by formalin injection. Formalin injection had no effect on mEPSC or mIPSC amplitudes in either sex. Pain-induced changes in mEPSC frequency in putative CRH neurons were phase-dependent. Results show that excitatory synaptic inputs to BST CRH neurons are temporally enhanced along with behavioral sex differences in pain response, suggesting that pain signals alter the BST CRH neurons excitability in a sex-dependent manner.

View all citing articles on Scopus

^∗: Present address: Department of Anatomy, Osaka Medical College, 2–7 Daigaku-Cho, Takatsuki, Osaka (569), Japan.

View full text

Research reportDistribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex

Abstract

Brain Research

Brain Research

Regul. Peptides

Neuroscience

Brain Research

Neurosci. Lett.

Electroencephalogr. Clin. Neurophysiol.

Brain Research

Neuroscience

Brain Research

Brain Research

Neurosci. Lett.

Neuroscience

Neuroscience

Brain Research

Brain Research

Physiol. Behav.

Peptides

Regul. Peptides

Neurosci. Lett.

Neuroscience

Life Sci.

Neuroscience

Peptides

Life Sci.

Physiol. Behav.

Brain Research

Brain Research

Neuroscience

Brain Research

Brain Research

Brain Research

An autoradiographic analysis of the different ascending projections of the dorsal and median raphe nuclei in the rat

J. Comp. Neurol.

Cytological Technique

Effect of hypothalamic lesion at different loci on development of hyperinsulinemia and obesity in the weanling rat

J. Comp. Neurol.

Growth and obesity in male rat after placement of ventromedial hypothalamic lesion at four different ages

J. Endocrinol.

Intraventricular corticotropin releasing factor enhances behavioural effects of novelty

Life Sci.

Mechanism of the development of obesity in animals with hypothalamic lesions

Physiol. Rev.

Corticotropin releasing factor: actions on the sympathetic nervous system and metabolism

Endocrinology

Cholinergic projections from the basal forebrain to the basolateral amygdaloid complex: a combined retrograde fluorescent and immunohistochemical study

J. Comp. Neurol.

New facts concerning the role played by the ventromedial nucleus in control of estrus cycle duration and sexual receptivity in the rat

Neuroendocrinology

Ontogeny of cholecystokinin-8-containing neuron system of the rat: an immunohistochemical analysis. I. Forebrain and upper brain stem

J. Comp. Neurol.

The connections of the amygdala

J. Neurol. Neurosurg. Psychiat.

The distribution of substance P immunoreactive fibres in the rat central nervous system

J. Comp. Neurol.

Cholecystokinin octapeptide-containing picomole injections into the cerebral ventricles of sheep suppress feeding

Science

Descending input from the pneumotaxic system to the lateral respiratory nucleus of the medulla. An anatomical study with the horseradish peroxidase technique

Neurosci. Lett.

The amygdaloid projection field in the rat as studied with the cupric-silver method

Comparison of fixation and penetration enhancement technique for use in ultrastructural immunocytochemistry

J. Histochem. Cytochem.

Catecholamine innervation of the basal forebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex

J. Comp. Neurol.

Research report
Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex