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Differential activation of anatomically defined neuronal subpopulations in the amygdala during fear conditioning and extinction

Senn, Verena. Differential activation of anatomically defined neuronal subpopulations in the amygdala during fear conditioning and extinction. 2009, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_8782

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Abstract

The amygdala is a key structure of the neuronal circuitry mediating expression
and extinction of conditioned fear. However, fear memories are thought to be
encoded in a larger network comprising the medial prefrontal cortex (mPFC)
and the hippocampus (HC). Thus, amygdala projections to the mPFC and to
the HC are likely to be involved in fear learning, yet the cellular substrates of
that learning remain unknown. To examine the role of identified amygdala
projection neurons in the expression and extinction of conditioned fear
responses, I used a combination of in vivo retrograde tracing techniques and
analysis of expression of the activity-dependent immediate early genes (IEGs)
cFos and Zif268. I show that amygdala neurons projecting to the mPFC or to
the HC exhibit differential cFos and Zif268 expression in fear conditioned
animals compared with non-conditioned control animals and with animals
subjected to extinction. In particular, extinction resulted in a selective induction
of cFos in mPFC projecting neurons. A more detailed analysis revealed that
neurons projecting to the infralimbic subdivision of the mPFC (IL), but not those
projecting to the prelimbic subdivision (PL), account for the specific cFos
expression in mPFC-projecting neurons following extinction. To investigate the
physiological correlates of fear extinction in anatomically defined
subpopulations of amygdala projection neurons I used an electrophysiological
ex vivo approach. In these experiments, I recorded from identified BA neurons
projecting to PL or IL in slices obtained from mice subjected to extinction.
Extinction differentially affects intrinsic properties of PL- and IL-projecting cells.
While there was no change in PL-projecting neurons, IL-projecting BA cells
showed a learning-related increase in spike half-width and a concomitant
decrease in the fast after-hyperpolarization (AHPfast). In control animals, spike
half-width and AHPfast were controlled by the activation of voltage-dependent
potassium channels (VDPCs) and large-conductance Ca2+ dependent
potassium channels (BK-channels). After extinction training only VDPCs
contribute to the AHPfast in IL-projecitng cells. This indicates a specific
modulation of BK-channels in IL-projecting neurons following extinction
learning. Our findings suggest that a change in the balance of activity between
IL- and PL-projecting BA neurons may be involved in the extinction of
conditioned fear.
Advisors:Lüthi, Andreas
Committee Members:Bettler, Bernhard
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
Item Type:Thesis
Thesis no:8782
Bibsysno:Link to catalogue
Number of Pages:95
Language:German
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:08 Jan 2010 08:25

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