Abstract
It is generally understood that genetic mechanisms contribute to pathological anxiety and that C57BL/6 (B6) and DBA/2J (D2) mice, inbred strains differing markedly in their anxiety-like behaviors, may represent a model system to study these contributions. Because lateral/basolateral amygdala (BLA) GABAA receptors help regulate anxiety-like behaviors, we have tested the hypothesis that differences in receptor function/expression may be related to strain-specific differences in experimentally measured anxiety. First, we demonstrated that anxiety-like behaviors in two separate assays were more substantial in D2 mice. Then, using whole-cell electrophysiology of isolated neurons, we found that D2 BLA neurons expressed significantly greater GABA-gated responses than B6 BLA neurons. This was specific for GABAA receptors, because N-methyl-d-aspartate-gated responses were similar between strains. At the molecular level, this increased GABAA function was associated with higher levels of α2 subunit mRNA expression in D2 BLA. Finally, to understand the ramifications of these functional and molecular biological differences, we examined both electrically evoked GABAergic responses and spontaneous synaptic currents using whole-cell recordings with in vitro slice preparations. Presynaptic GABAergic function was more robust in D2 compared with B6 slices. Together, our findings suggest that genetic mechanisms differentially represented in these two inbred mouse strains lead to robust differences in pre- and postsynaptic aspects of amygdala GABAergic function.
Footnotes
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This work is supported in part by National Institutes of Health Grant AA014445 (to B.A.M.), a pilot grant from the “Integrated Neuroscience Initiative on Alcoholism: Stress, Anxiety, and Alcohol Abuse” (to B.A.M.), and National Institute on Alcohol Abuse and Alcoholism Grant T32 AA007565 (to D.W.D.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.100552.
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ABBREVIATIONS: QTL, quantitative trait loci; BLA, lateral/basolateral amygdala; B6, C57BL/6 mouse strain; D2, DBA/2J mouse strain; IPSC, inhibitory postsynaptic current; mIPSC, miniature IPSC; QX314-Cl, lidocaine; NMDA, N-methyl-d-aspartate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PCR, polymerase chain reaction; TTX, tetrodotoxin.
- Received December 23, 2005.
- Accepted April 27, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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