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L-type Voltage-Gated Calcium Channels in Fear Conditioning, Fear Extinction, and Amygdala Neurophysiology.

dc.contributor.authorMcKinney, Brandon Chaden_US
dc.date.accessioned2010-06-03T15:49:59Z
dc.date.availableNO_RESTRICTIONen_US
dc.date.available2010-06-03T15:49:59Z
dc.date.issued2010en_US
dc.date.submitteden_US
dc.identifier.urihttps://hdl.handle.net/2027.42/75966
dc.description.abstractFear conditioning is a form of learning in which an initially neutral stimulus (e.g., tone or context) comes to be feared after being paired with an aversive stimulus (e.g., shock). After pairing, the neutral stimulus alone can elicit fear responses (e.g., freezing behavior, autonomic arousal, stress hormone release). The initially neutral stimulus is referred to as the "conditioned stimulus" (CS) once it is able to bring about fear responses on its own, the aversive stimulus is the "unconditioned stimulus" (US), and the fear responses elicited by the CS are the "conditioned responses" (CRs). Fear extinction is a process by which the previously conditioned fear responses can be reduced by repeated presentation of the CS alone, in the absence of the aversive US. Fear conditioning and fear extinction are both critically dependent on the amygdala, a medial temporal lobe brain structure. Interestingly, it has been previously demonstrated that L-type voltage-gated calcium channels (L-VGCCs) have a role in fear conditioning, fear extinction, and amygdala neurophysiology. All of the studies implicating L-VGCCs in these phenomena used L-VGCC antagonists to demonstrate the role for L-VGCCs. There are two brain-expressed L-VGCCs, Cav1.2 and Cav1.3, both of which are the targets of currently-available L-VGCC antagonists. In this dissertation, I address the contribution of each of these L-VGCCs to fear conditioning, fear extinction, and amygdala neurophysiology using mouse models in which the genes for either Cav1.2 or Cav1.3 deleted. First, I demonstrate that Cav1.3, but not Cav1.2, mediates consolidation of fear conditioning. Next, I show that neither Cav1.2 nor Cav1.3 alone is necessary for fear extinction. Instead, I find that the L-VGCC antagonist nifedipine used in the previous experiments implicating L-VGCCs in fear extinction impairs locomotion and induces an aversive state. Further, I demonstrate that this aversive state can enter into associations with stimuli present at the time that it is experienced, suggesting that previous studies using nifedipine were likely confounded by drug toxicity. Finally, I show that Cav1.3 mediates long-term potentiation of afferents to the basolateral amygdala (BLA) as well as the afterhyperpolarization in principal neurons of the BLA.en_US
dc.format.extent1349645 bytes
dc.format.extent1373 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_USen_US
dc.subjectFear Conditioningen_US
dc.subjectL-type Voltage-gated Calcium Channelsen_US
dc.subjectCaV1.2en_US
dc.subjectCaV1.3en_US
dc.subjectFear Extinctionen_US
dc.subjectFear Consolidationen_US
dc.titleL-type Voltage-Gated Calcium Channels in Fear Conditioning, Fear Extinction, and Amygdala Neurophysiology.en_US
dc.typeThesisen_US
dc.description.thesisdegreenamePhDen_US
dc.description.thesisdegreedisciplineNeuroscienceen_US
dc.description.thesisdegreegrantorUniversity of Michigan, Horace H. Rackham School of Graduate Studiesen_US
dc.contributor.committeememberMurphy, Geoffrey G.en_US
dc.contributor.committeememberMaren, Stephen A.en_US
dc.contributor.committeememberMeisler, Miriam H.en_US
dc.contributor.committeememberSeasholtz, Audrey F.en_US
dc.contributor.committeememberSutton, Michael Marken_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/75966/1/bcmckinn_1.pdf
dc.owningcollnameDissertations and Theses (Ph.D. and Master's)


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