Author ORCID Identifier
0000-0002-9738-7621
Date of Graduation
5-2017
Document Type
Dissertation (PhD)
Program Affiliation
Neuroscience
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Shane Cunha, Ph.D
Committee Member
Ruth Heidelberger, MD, Ph.D
Committee Member
Neal Waxham, Ph.D
Committee Member
Vasanthi Jayaraman, Ph.D
Committee Member
Qingchun Tong, Ph.D.
Abstract
Abstract
THE EXTERNAL GLOBUS PALLIDUS: BIDIRECTIONAL CONTROL OVER ANXIETY-RELATED BEHAVIOR MEDIATED BY CRFR1
Albert Lee Joseph Hunt, Jr., B.S.
Advisory Professor: Shane Cunha, Ph.D.
Corticotropin-releasing factor receptor 1 (CRFR1), the principle receptor responsible for the anxiogenic activity of the stress peptide CRF, is abundantly expressed in the external globus pallidus (GPe) raising the question whether activity in the GPe is altered in response to stress. I show that CRFR1 expressing neurons are of the “prototypic” subtype of GPe neurons. I provide evidence of novel circuits from CRF neurons in stress-responsive nuclei, including the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CeA), that provide excitatory input to the GPe. Additionally, I show that activation of CRFR1 neurons using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) increases anxiety-related behavior and movement. I show that anxiety-related behavior and movement are decreased in response to activation of Npas1+ neurons, a class of neuron in the GPe that are primarily of the “arkypallidal” subtype. My evidence indicates that CRF neurons may project to the GPe to modulate anxiety-related behavior and movement through differential synaptic input to distinct GPe neuronal subtypes. CRF to GPe circuits provide possible therapeutic avenues to treat anxiety disorders comorbid with basal ganglia neurodegenerative diseases that cause aberrant activity in the GPe such as Parkinson’s disease.
Keywords
GPe, external globus pallidus, CRF, CRFR1, anxiety, behavior, mice, parkinson's disease, psychiatric