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Serotonergic innervation of the amygdala: targets, receptors, and implications for stress and anxiety

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Abstract

The amygdala is a core component of neural circuits that mediate processing of emotional, particularly anxiety and fear-related stimuli across species. In addition, the nuclear complex plays a key role in the central nervous system stress response, and alterations in amygdala responsivity are found in neuropsychiatric disorders, especially those precipitated or sustained by stressors. Serotonin has been shown to shape and fine-tune neural plasticity in development and adulthood, thereby allowing for network flexibility and adaptive capacity in response to environmental challenges, and is implicated in the modulation of stimulus processing and stress sensitivity in the amygdala. The fact that altered amygdala activity patterns are observed upon pharmacological manipulations of serotonergic transmission, as well as in carriers of genetic variations in serotonin pathway-associated signaling molecules representing risk factors for neuropsychiatric disorders, underlines the importance of understanding the role and mode of action of serotonergic transmission in the amygdala for human psychopathology. Here, we present a short overview over organizational principles of the amygdala in rodents, non-human primates and humans, and review findings on the origin, morphology, and targets of serotonergic innervation, the distribution patterns and cellular expression of serotonin receptors, and the consequences of stress and pharmacological manipulations of serotonergic transmission in the amygdala, focusing particularly on the extensively studied basolateral complex and central nucleus.

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Abbreviations

5-HT:

5-Hydroxytryptamin, serotonin

5-HTR:

Serotonin receptor(s)

5-HTT:

Serotonin transporter

AMPA:

Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid

BL:

Basolateral nucleus

BLA:

Basolateral amygdala

BLC:

Basolateral complex

BM:

Basomedial nucleus

BNST:

Bed nucleus of the stria terminalis

CaMK:

Calcium/calmodulin-dependent protein kinase II

CB:

Calbindin

CB1:

Cannabinoid-receptor 1

CCK:

Cholecystokinin

Ce:

Central nucleus

CeL:

Lateral central nucleus

CeLc:

Lateral capsular subdivision of the central nucleus

CeM:

Medial central nucleus

CNS:

Central nervous system

Co:

Cortical nucleus

CR:

Calretinin

CRF:

Corticotropin releasing factor

DR:

Dorsal raphe nuclei

ENK:

Enkephalin

ERK:

Extracellular signal-regulated kinase(s)

GABA:

Gamma-amino butyric acid

GAD:

Glutamic acid decarboxylase

IC:

Intercalated cells

ICps:

Paracapsular intercalated cell islands

IHC:

Immunohistochemistry

i.p.:

Intraperitoneal

ir:

Immunoreactive

ISH:

In situ hybridization

La:

Lateral nucleus

Leu-ENK:

Leu-enkephalin

Me:

Medial nucleus

Met-ENK:

Met-enkephalin

MR:

Median raphe nuclei

NMDA:

N-methyl-d-aspartate

NK-1:

Neurokinin-1 receptor

NPY:

Neuropeptide Y

PAC:

Periamygdaloid cortex

PL:

Paralaminar nucleus

PV:

Parvalbumin

SOM:

Somatostatin

SSRI:

Selective serotonin reuptake inhibitor

Tph2:

Tryptophan hydroxylase 2

VIP:

Vasoactive intestinal polypeptide

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Acknowledgments

The writing of this article and the authors’ related research were supported by the Deutsche Forschungsgemeinschaft (SFB 581/B9 and Z3, RTG 1253, SFB TRR 58/A1 and A5, KFO 125).

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  1. Maria Steinke

    Present address: Department of Tissue Engineering and Regenerative Medicine, University of Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany

Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070, Wuerzburg, Germany

    Esther Asan & Maria Steinke

  2. Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstr. 15, 97080, Wuerzburg, Germany

    Klaus-Peter Lesch

  3. Department of Neuroscience, School for Mental Health and Neuroscience (MHENS), Maastricht University, Universiteitssingel 40, 6229, ER Maastricht, The Netherlands

    Klaus-Peter Lesch

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Asan, E., Steinke, M. & Lesch, KP. Serotonergic innervation of the amygdala: targets, receptors, and implications for stress and anxiety. Histochem Cell Biol 139, 785–813 (2013). https://doi.org/10.1007/s00418-013-1081-1

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