Kappa opioid receptor modulation of neurotransmission in the amygdala
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Crowley, Nikki. Kappa Opioid Receptor Modulation of Neurotransmission In the Amygdala. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School, 2015. https://doi.org/10.17615/emjn-0f63APA
Crowley, N. (2015). Kappa opioid receptor modulation of neurotransmission in the amygdala. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/emjn-0f63Chicago
Crowley, Nikki. 2015. Kappa Opioid Receptor Modulation of Neurotransmission In the Amygdala. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/emjn-0f63- Last Modified
- March 19, 2019
- Creator
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Crowley, Nikki
- Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
- Abstract
- Kappa opioid receptors (KORs) and their endogenous ligand, dynorphin, have been implicated in a variety of neuropsychiatric disorders including anxiety and alcohol addiction. Here, we demonstrate the function and role of KORs in the bed nucleus of the stria terminalis (BNST), a key brain region involved in these diseases. In the first series of experiments, we show that KORs in the BNST inhibit glutamate release via a presynaptic, p38- and calcium- dependent mechanism. This synaptic inhibition is specific to basolateral amygdala (BLA) inputs, a previously identified key pathway in rodent models of anxiety-related behaviors. Additionally, we identified a frequency-dependent, light-evoked, local dynorphin-induced heterosynaptic plasticity of glutamate inputs to the BNST, allowing for optogenetic control of peptidergic transmission. We found differential KOR modulation of the BLA-BNST input based on the postsynaptic neurochemical identity. Collectively, these results demonstrate a local dynorphin- and KOR- dependent mechanism of inhibiting an anxiolytic pathway, providing a discrete therapeutic target for treatment of anxiety disorders. In the second series of experiments, we show that following chronic intermittent iv ethanol exposure (CIE), a model of alcohol exposure, KORs differentially modulate glutamate and GABA in the BNST. KOR inhibition of electrically-evoked glutamate inputs is decreased, while KOR inhibition of electrically-evoked GABA inputs is increased, despite overall properties of glutamatergic and GABAergic transmission remaining intact. This change in synaptic physiology is complementary to a KORdependent behavioral change: mice exposed to ethanol show decreased social preference as compared to air exposed, an effect which is partially rescued by systemic pre-administration of the KOR antagonist JDTic. Taken together, these experiments demonstrate KOR-dependent alterations of synaptic transmission in the BNST following CIE, making the BNST a potential site of action for KOR targeted therapies related to alcohol and anxiety. Jointly, these experiments expand our understanding of how key peptidergic transmission in the extended amygdala can play a role in anxiety and addiction related diseases.
- Date of publication
- December 2015
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- In Copyright
- Advisor
- Kash, Thomas
- Philpot, Benjamin
- Stuber, Garret
- Manis, Paul B.
- Besheer, Joyce
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2015
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- Place of publication
- Chapel Hill, NC
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- There are no restrictions to this item.
- Date uploaded
- January 21, 2016
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