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Dopaminergic modulation of synaptic transmission and plasticity in the lateral amygdala

Bissière, Stéphanie. Dopaminergic modulation of synaptic transmission and plasticity in the lateral amygdala. 2004, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_7358

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Abstract

Fear conditioning is one of the most powerful and widely used paradigm to investigate the mechanisms of associative learning in animals (LeDoux, 2000; Maren, 2001). Behavioral and in vivo electrophysiological evidence indicate that induction of long-term-potentiation (LTP), a form of associative, activity-dependent synaptic plasticity in the lateral amygdala (LA), a brain structure tightly controlled by GABAergic inhibition, underlies the acquisition of fear conditioning (Lang and Pare, 1997; Pare et al., 2003). Dopamine (DA), the most abundant catecholemine in the brain, is released in the amygdala upon stress. DA receptor activation is required for the potentiation of sensory evoked neuronal activity in the LA during conditioning (Rosenkranz and Grace, 2002). Conversely, intra-amygdala injections of DA receptor antagonists prevents the acquisition of fear conditioning (Greba et al., 2001; Greba and Kokkinidis, 2000; Guarraci et al., 2000; Guarraci et al., 1999). The cellular and synaptic mechanisms underlying the dopaminergic modulation of fear conditioning and synaptic plasticity are, however, still unknown. In the first part of my work, I showed that DA gates the induction of LTP in the mouse LA by supressing feed-forward inhibition mediated by local interneurons. The action of DA on synaptic plasticity depended on the activation of D2 receptors and appeared to be twofold. First, it reduced the quantal content at inhibitory synapses, thereby decreasing inhibitory synaptic transmission and second, it facilitated inhibition onto interneurons by depolarizing interneurons involved in disinhibition. In the second part of my work I investigated the role of DA on spontaneous inhibitory network activity. Consistent with previous in vivo data showing that systemic administration of DA agonists in the LA increases the spontaneous firing of interneurons
(Rosenkranz and Grace, 1999), we found that bath application of DA increased the frequency of spontaneous inhibitory transmission recorded from projection neurons. In contrast to the gating of LTP, this effect required the activation of D1 and D2 receptors in synergy. Preliminary data suggested that the D1 receptor-mediated increase in spontaneous inhibitory transmission did not involve cAMP-mediated intracellular signaling mechanisms.
Advisors:Lüthi, Andreas
Committee Members:Rüegg, Markus A.
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Rüegg, Markus A.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7358
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:121
Language:English
Identification Number:
Last Modified:22 Apr 2018 04:30
Deposited On:13 Feb 2009 15:23

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