Botta, Paolo. Modulating anxiety with extrasynaptic inhibition. 2014, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10873
Classically, sensory cortico-thalamic information is processed and transferred from the basolateral to the central nucleus of the amygdala; the latter of which is considered this circuit’s primary output structure. Central amygdala neurons thereby project to brain regions involved in the expression of fear and anxiety. Interestingly, it was recently found that fear conditioning induced cell-type-specific plasticity in three distinct neuronal subtypes of the central amygdala. In addition to a phasic change response, the spontaneous firing of defined neuronal populations was changed and predicted fear generalization of behavioral responses to an unconditional cue.
Yet, the direct involvement of particular neuronal classes on anxiety and fear generalization to an unconditioned sensory stimulus remains elusive. Further, mechanisms underlying such changes in tonic activity in central amygdala followed by a traumatic experience are not known. It has been shown in other brain areas that tonic activity can be modulated by GABAergic inhibition. In particular, GABAergic tonic currents are well-suited for this task because they exert a continuous dampening of cell-excitability and reduce the integration of excitatory inputs within neurons.
My PhD research focused predominantly on causally defining a specific physiological mechanism by which the change in tonic activity of defined neuronal CEA subtypes control behavioral emotional responses. To gain genetic access to these particular neuronal populations, a transgenic mouse line was used in combination with an array of state-of-the-art techniques. Here, we identify a specific cell-type located in the central nucleus of the amygdala as a key mediator of stress-induced anxiety and fear generalization. Moreover, we show that acute stress regulates the activity of these cells by tuning extrasynaptic inhibition mediated by specific alpha5 subunit containing GABAA receptors. Our findings demonstrate that the neuronal circuitries of fear and anxiety overlap in the central amygdala and indicate that complex changes in fear and anxiety behavior can be driven by discrete molecular mechanisms in distinct neuronal cell types
|Committee Members:||Mrsic-Flogel, Thomas|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI > Cellular mechanisms of learning and memory (Lüthi)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||119 S.|
|Last Modified:||30 Jun 2016 10:56|
|Deposited On:||05 Sep 2014 12:39|
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