Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of Ca(V)1.3 knockout mice.
Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel Ca(V)1.3 is deleted (Ca(V)1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which Ca(V)1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from Ca(V)1.3 knockout mice and wild-type littermates to explore the role of Ca(V)1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in Ca(V)1.3 knockout mice. Additionally, we found that BLA principal neurons from Ca(V)1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of Ca(V)1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear.
McKinney
Brandon C
BC
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109-5619, United States.
Sze
Wilson
W
Lee
Benjamin
B
Murphy
Geoffrey G
GG
D000200:Action Potentials / Q000502:physiology*; D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type