Abstract

Inhaled anesthetics impair learning and memory by mechanisms that remain unknown. GABAA and NMDA receptors are considered prime candidates because a wide variety of inhaled and injected anesthetics alter the activity of these receptors, and because some injected agents that impair learning and memory (e.g., midazolam and ketamine) act specifically through these receptors. Our proposal tests the hypothesis that inhaled anesthetics suppress memory formation by altering GABAA and or NMDA receptor function. We will test this hypothesis by comparing the effects of inhaled anesthetics and specific modulators of GABAA or NMDA receptors on synaptic transmission, synaptic plasticity, and memory. Our subjects will be wild-type mice and mice harboring point mutations that render specific GABAA or NMDA receptors insensitive to inhaled agents. Because the hippocampus is a well-characterized cortical structure and is implicated in the formation of explicit memories, experiments will focus on receptors that are expressed in the hippocampus, on hippocampal synapses, and on hippocampal-dependent learning.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM047818-13
Application #
7270610
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
13
Fiscal Year
2006
Total Cost
$165,261
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Cai, Xiaoyun; Huang, Huizhen; Kuzirian, Marissa S et al. (2016) Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling. Genesis 54:29-37
Zarnowska, E D; Rodgers, F C; Oh, I et al. (2015) Etomidate blocks LTP and impairs learning but does not enhance tonic inhibition in mice carrying the N265M point mutation in the beta3 subunit of the GABA(A) receptor. Neuropharmacology 93:171-178
Burkat, Paul M; Lor, Chong; Perouansky, Misha et al. (2014) Enhancement of ?5-containing ?-aminobutyric acid type A receptors by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) is abolished by the ?3(N265M) mutation. Anesth Analg 119:1277-84
Iyer, Sangeetha V; Chandra, Dave; Homanics, Gregg E (2014) GABAA-R ?4 subunits are required for the low dose locomotor stimulatory effect of alphaxalone, but not for several other behavioral responses to alphaxalone, etomidate or propofol. Neurochem Res 39:1048-56
Blednov, Yuri A; Benavidez, Jill M; Homanics, Gregg E et al. (2012) Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor ?1 subunit. J Pharmacol Exp Ther 340:317-29
Borghese, Cecilia M; Blednov, Yuri A; Quan, Yu et al. (2012) Characterization of two mutations, M287L and Q266I, in the ?1 glycine receptor subunit that modify sensitivity to alcohols. J Pharmacol Exp Ther 340:304-16
Pearce, R A; Duscher, P; Van Dyke, K et al. (2012) Isoflurane impairs odour discrimination learning in rats: differential effects on short- and long-term memory. Br J Anaesth 108:630-7
Blednov, Y A; Borghese, C M; McCracken, M L et al. (2011) Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive ýý2-containing GABA(A) receptors. J Pharmacol Exp Ther 336:145-54
Werner, D F; Swihart, A; Rau, V et al. (2011) Inhaled anesthetic responses of recombinant receptors and knockin mice harboring ?2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J Pharmacol Exp Ther 336:134-44
Chang, Ki-Young; Park, Young-Gyun; Park, Hye-Yeon et al. (2011) Lack of CaV3.1 channels causes severe motor coordination defects and an age-dependent cerebellar atrophy in a genetic model of essential tremor. Biochem Biophys Res Commun 410:19-23

Showing the most recent 10 out of 167 publications