This project is designed to identify stress induced changes to inhibitory GABAergic circuitry in the basolateral amygdala (BLA) of an animal model of stress-enhanced fear learning (SEFL). It has been shown that GABAergic inhibition is predominately responsible for the regulation of functional activity in many brain regions, including the BLA. The BLA is the brain region where emotional memory is encoded and stored. Alcohol abuse and alcoholism have a negative impact upon society and it has been shown that, compared to the general population, there is a significantly increased incidence of alcohol abuse and alcoholism in subpopulations diagnosed with sever anxiety disorders such as post-traumatic stress disorder (PTSD). The SEFL animal model mimics some of the major characteristics of PTSD such as heightened sensitivity to fear learning and large increases in voluntary alcohol consumption. This proposal aims to: 1) identify putative functional changes in distinctly separate GABAergic inhibitory circuits in the BLA and 2) characterize specific alterations in g- aminobutyric acid A receptor (GABAAR) subunits. This research strategy is the basis of a multidisciplinary training plan designed to develop the trainee's expertise in animal behavioral conditioning, electrophysiological recording techniques, and molecular biology assays. This plan will utilize behavioral conditioning to generate the SEFL rodent model and the appropriate controls. Episodic stimulation of two separate groups of GABAergic interneurons will be done in order to record and measure changes to evoked inhibitory currents generated by two inhibitory circuits of the BLA. In parallel experiments, Western blotting techniques will be done t compare SEFL conditioning induced alterations in surface and intracellular levels of GABAAR subunits between SEFL and control animals. It is expected that the proposed research will lead to a better understanding of how a traumatic stressor, that sensitizes an animal to novel fears and induces large amounts of alcohol consumption, is able to affect GABAergic circuitry in the BLA. This multidisciplinary training will prepare the trainee for an independent academic career focused on studying the behavioral, functional and molecular mechanisms of stress and alcohol abuse.
Post-traumatic stress disorder (PTSD) and other severe anxiety disorders have an alarmingly high rate of coincidental alcohol abuse and alcoholism. While stress and anxiety disorders are the target of much biomedical research very little is known about the physiological mechanism of how a traumatic stressor can lead to abnormal fear responses or exceedingly high rates of alcoholism. This research proposal utilizes a rodent model of stress-enhanced fear learning that mimics major characteristics of PTSD, to study brain region specific changes that are involved in the manifestation of enhanced fear learning.
|Liang, Jing; Lindemeyer, A Kerstin; Suryanarayanan, Asha et al. (2014) Plasticity of GABA(A) receptor-mediated neurotransmission in the nucleus accumbens of alcohol-dependent rats. J Neurophysiol 112:39-50|