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Brain Struct Funct. 2018 Jul;223(6):2685-2698. doi: 10.1007/s00429-018-1652-y. Epub 2018 Mar 23.

Paraventricular hypothalamic and amygdalar CRF neurons synapse in the external globus pallidus.

Author information

1
The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Center for Metabolic and Degenerative Diseases, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
2
Graduate Program in Neuroscience, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, 77030, USA.
3
Department of Neurobiology and Anatomy, McGovern Medical School, Houston, TX, 77030, USA.
4
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
5
The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, Center for Metabolic and Degenerative Diseases, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Nicholas.J.Justice@uth.tmc.edu.
6
Graduate Program in Neuroscience, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, 77030, USA. Nicholas.J.Justice@uth.tmc.edu.

Abstract

Stress evokes directed movement to escape or hide from potential danger. Corticotropin-releasing factor (CRF) neurons are highly activated by stress; however, it remains unclear how this activity participates in stress-evoked movement. The external globus pallidus (GPe) expresses high levels of the primary receptor for CRF, CRFR1, suggesting the GPe may serve as an entry point for stress-relevant information to reach basal ganglia circuits, which ultimately gate motor output. Indeed, projections from CRF neurons are present within the GPe, making direct contact with CRFR1-positive neurons. CRFR1 expression is heterogenous in the GPe; prototypic GPe neurons selectively express CRFR1, while arkypallidal neurons do not. Moreover, CRFR1-positive GPe neurons are excited by CRF via activation of CRFR1, while nearby CRFR1-negative neurons do not respond to CRF. Using monosynaptic rabies viral tracing techniques, we show that CRF neurons in the stress-activated paraventricular nucleus of the hypothalamus (PVN), central nucleus of the amygdala (CeA), and bed nucleus of the stria terminalis (BST) make synaptic connections with CRFR1-positive neurons in the GPe an unprecedented circuit connecting the limbic system with the basal ganglia. CRF neurons also make synapses on Npas1 neurons, although the majority of Npas1 neurons are arkypallidal and do not express CRFR1. Interestingly, prototypic and arkypallidal neurons receive different patterns of innervation from CRF-rich nuclei. Hypothalamic CRF neurons preferentially target prototypic neurons, while amygdalar CRF neurons preferentially target arkypallidal neurons, suggesting that these two inputs to the GPe may have different impacts on GPe output. Together, these data describe a novel neural circuit by which stress-relevant information carried by the limbic system signals in the GPe via CRF to influence motor output.

KEYWORDS:

CRF; CRFR1; CRH; CRHR1; Globus pallidus; Stress

PMID:
29569009
PMCID:
PMC5997534
[Available on 2019-07-01]
DOI:
10.1007/s00429-018-1652-y
[Indexed for MEDLINE]

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