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

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.

SUBMITTER: Hunt AJ

PROVIDER: S-EPMC5997534 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Hunt Albert J AJ Dasgupta Rajan R Rajamanickam Shivakumar S Jiang Zhiying Z Beierlein Michael M Chan C Savio CS Justice Nicholas J NJ

Brain structure & function 20180323 6

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 ...[more]

PMID: 29569009

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Project description:Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction.Significance statementUntil recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the markers parvalbumin and Npas1. Our study provides evidence that parvalbumin and Npas1 neurons have different topologies within the basal ganglia.

Dataset Information

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

Publications

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

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