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bioRxiv · 10.1101/557256

Polymodal Sensory Thalamic Inputs to the Rat Lateral Amygdala are Facilitated by Chronic Ethanol Exposure and Regulate Withdrawal-associated Anxiety

Morales, M.·McGinnis, M. M.·Chappell, A. M.·Parrish, B. C.·McCool, B. A.
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Abstract

Thalamic projections to the lateral amygdala regulate the acquisition of conditioned aversive and reward-related behaviors. Recent work suggests that exposure to chronic ethanol up-regulates presynaptic function of lateral amygdala stria terminalis inputs which contain projections from somatosensory thalamic nuclei. To understand potential contributions by thalamic inputs and their role in the expression of withdrawal-associated aversive behaviors, we integrated optogenetic and chemogenetic approaches with in vitro measures of synaptic function and anxiety-like behavior. We found that expression of Channelrhodopsin in the caudal extension of the posterior thalamic group (cPO) produced monosynaptic glutamatergic synaptic responses in lateral amygdala principal neurons that could be inhibited by co-expression of the hM4-Gi-DREADD. Chronic ethanol exposure increased glutamate release from these cPO terminals but did not impact inhibition by the DREADD agonist, CNO. Systemic injection of CNO specifically reduced withdrawal-related increases in anxiety-like behaviors in animals expressing the Gi-DREADD in cPO. And, microinjection of CNO directly into the lateral amygdala mimicked this anti-anxiety effect. These findings suggest that the cPO-LA circuit is vulnerable to chronic ethanol exposure and plays an important role in regulating anxiety-like behavior following chronic ethanol exposure.

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Morales, M., McGinnis, M. M., Chappell, A. M., Parrish, B. C., McCool, B. A.. 2019-02-21. Polymodal Sensory Thalamic Inputs to the Rat Lateral Amygdala are Facilitated by Chronic Ethanol Exposure and Regulate Withdrawal-associated Anxiety. https://doi.org/10.1101/557256

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