The amygdala is known to play a critical role in emotional responses particularly fear, in both humans and animals. The amygdala and its afferent and efferent connections comprise a major component of the auditory fear conditioning circuitry. The long-term objective of this research is to characterize pre- and postsynaptic modifications in amygdala glutamatergic neurotransmission underlying the expression of learned fear. Preliminary data show significant alterations in synaptic transmission in the internal capsule (IC) fiber pathway from the medial geniculate to the dorsal lateral amygdala recorded in vitro in amygdala slices from paired fear conditioned but not unpaired control animals. The proposed experiments using the fear-potentiated startle paradigm will test the hypothesis that lasting potentiation of synaptic transmission occurs at particular synapses within the fear conditioning intraamygdala circuitry. The following specific aims will be addressed using whole cell patch recording in amygdala slice preparations from three populations of animals. naive control, unpaired control and paired fear conditioned animals: 1) Characterize the modifications in synaptic transmission and membrane conductance underlying fear conditioning and determine the pre- and post-synaptic changes in N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated synaptic transmission in animals exposed to a paired conditioned stimulus (CS) and aversive stimulus (UCS) with those exposed to the same information but in an unpaired paradigm and 2) trace the information flow through the amygdala by comparing in the three populations of animals the synaptic modifications occurring in glutamatergic transmission at different synapses in the amygdala fear conditioning circuitry. The results of the proposed experiments will enhance our understanding of the membrane mechanisms underlying emotional learning at the membrane and whole cell level and provide important information about changes in the essential elements of interneuronal communication within a key structure involved in emotion, the amygdala. Ultimately the proposed studies may provide insight into potential therapeutic strategies in the treatment of neuropsychiatric disorders such as anxiety, phobia, schizophrenia and in particular posttraumatic stress disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH058327-03
Application #
6186509
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Program Officer
Anderson, Kathleen C
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$171,575
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Orozco-Cabal, Luis; Liu, Jie; Pollandt, Sebastian et al. (2008) Dopamine and corticotropin-releasing factor synergistically alter basolateral amygdala-to-medial prefrontal cortex synaptic transmission: functional switch after chronic cocaine administration. J Neurosci 28:529-42
Gallagher, Joel P; Orozco-Cabal, Luis F; Liu, Jie et al. (2008) Synaptic physiology of central CRH system. Eur J Pharmacol 583:215-25
Orozco-Cabal, Luis; Pollandt, Sebastian; Liu, Jie et al. (2006) Regulation of synaptic transmission by CRF receptors. Rev Neurosci 17:279-307
Fu, Yu; Shinnick-Gallagher, Patricia (2005) Two intra-amygdaloid pathways to the central amygdala exhibit different mechanisms of long-term potentiation. J Neurophysiol 93:3012-5
Scott, Michael T; Shinnick-Gallagher, Patricia (2005) Internuclear synapse in the amygdala is not facilitated in fear conditioning. Synapse 55:67-70
Schroeder, Bradley W; Shinnick-Gallagher, Patricia (2005) Fear learning induces persistent facilitation of amygdala synaptic transmission. Eur J Neurosci 22:1775-83
Schroeder, Bradley W; Shinnick-Gallagher, Patricia (2004) Fear memories induce a switch in stimulus response and signaling mechanisms for long-term potentiation in the lateral amygdala. Eur J Neurosci 20:549-56
Liu, Jie; Yu, Baojian; Neugebauer, Volker et al. (2004) Corticotropin-releasing factor and Urocortin I modulate excitatory glutamatergic synaptic transmission. J Neurosci 24:4020-9
Shinnick-Gallagher, Patricia; McKernan, Margaret G; Xie, Jiangang et al. (2003) L-type voltage-gated calcium channels are involved in the in vivo and in vitro expression of fear conditioning. Ann N Y Acad Sci 985:135-49
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

Showing the most recent 10 out of 13 publications