Vivian Costa Graduate Research Assistant Neuroscience Graduate Program University of Iowa Roy J and Lucille A Carver College of Medicine Department of Internal Medicine 500 EMRB Iowa City IA 52242 PHONE: 319 335 7574 FAX: 319 335 7623 vivian-costa@uiowa.edu

Hometown: Linden, NJ
Undergraduate: B.A. in biology from New York University, 2001
Graduate program: Neuroscience

Research interests:

Effects of ASIC3 overexpression in central neurons on proton-gated currents
and fear conditioning

Acid-evoked currents mediated by acid-sensing ion channels (ASICs) play an
important role in fear conditioning behaviors. Previous studies in mice
demonstrated that loss of ASIC1a expression disrupted both proton-gated
currents in central neurons and fear conditioning. To investigate the
effects of changing ASIC subunit composition, we generated transgenic mice
to expressing ASIC3 throughout the nervous system, including the brain,
where it is not normally detected. We hypothesized that overexpressingASIC3
in the brain would modify ASIC subunit composition and proton-gated
currents, and thereby alter fear conditioning. Transgenic ASIC3 protein
co-immunoprecipitated with endogenous ASIC1, suggesting insertion into ASIC
channel complexes. Like ASIC1a, ASIC3 was enriched in a synaptosomal
preparation. ASIC3 altered kinetic properties of proton-gated currents in
cultured cortical neurons, increasing the rate of desensitization, but not
current amplitude or pH-sensitivity. These changes generated currents with a
faster transient component and less total current. ASIC3 transgenic mice
exhibited impaired fear conditioning that was similar to that observed in
the ASIC1a knock-out mouse model. However, unconditioned fear was not
affected. These results suggest that altering the properties of proton-gated
currents interferes with normal neuronal function and impairs fear
conditioning.