The amygdala is widely believed to play an essential role in the attachment of emotional significance to learning and memory (LeDoux, 1994). The predominant excitatory neurotransmitter in the amygdala is glutamate, and an important, though less extensively studied, subtype of glutamate receptor is the ionotropic AMPA receptor (McDonald et al, 1989). The overall objective of this proposal is to characterize the native AMPA receptors in the amygdala by determining the electrophysiological properties of these receptors and correlating these properties with the specific receptor subunit composition (GluR1 -4).
Specific Aim #1 will be to characterize the electrophysiology of AMPA receptors in the lateral amygdala nucleus via whole-cell patch clamp recording from both amygdala slices and dissociated cells.
Specific Aim #2 will be to determine the receptor subunit composition of the same neurons characterized in S.A. #1 by the techniques of antisense RNA amplification and double-labeling with biocytin and GluR antibodies and correlate this with the electrophysiological data to determine the functional contribution of each subunit in native tissue.
Specific Aim #3 will analyze the role of AMPA receptors in the lateral amygdala in the expression of fear and anxiety by examining fear conditioning, a animal behavioral correlate of anxiety in humans; an attempt will be made to elucidate the underlying synaptic changes which accompany this emotion- based learning. Ultimately, these experiments will increase understanding of the circuitry underlying fear and anxiety and provide insight into therapeutic avenues for the treatment of human anxiety disorders, which represent a widespread and difficult challenge to the mental health community.
| Zinebi, Fatiha; Xie, Jiangang; Liu, Jie et al. (2003) NMDA currents and receptor protein are downregulated in the amygdala during maintenance of fear memory. J Neurosci 23:10283-91 |
| Zinebi, Fatiha; McKernan, Margaret; Shinnick-Gallagher, Patricia (2002) Expression of fear-conditioning is accompanied by increased paired-pulse depression within the amygdala. Pharmacol Biochem Behav 71:393-400 |
| Zinebi, F; Russell, R T; McKernan, M et al. (2001) Comparison of paired-pulse facilitation of AMPA and NMDA synaptic currents in the lateral amygdala. Synapse 42:115-27 |
