Identification of the Specific Pathways Within the Amygdalo-Striatal Circuitry Involved in the Transition From Controlled Drug Use to Compulsive Drug

Increasing evidence suggests that drug addiction stems from loss of control over maladaptive habits. At the neural system levels, the instantiation of drug seeking habits has been shown to be dependent on functional transitions in the amygdala driving functional transitions in the striatum. My research will aim to illuminate the cortico-amygdalo-striatal circuits that support these functional transitions underlying the development of maladaptive drug seeking habits in the rat.
More precisely, I will seek to test the hypothesis that the infralimbic (IL) cortex controls the functional shift from the basolateral to the central nucleus of the amygdala that is involved in the recruitment and maintenance, respectively, of dorsolateral striatum dopamine dependent drug seeking habits. In order to achieve this, I will deploy an array of contemporary neuroscience techniques, such as fibre photometry, optogenetics and RNAscope combined with novel models
of compulsive drug seeking habits in the rat to to identify the contribution of cortico-amygdala circuits and underlying cellular and molecular mechanisms to the the development of drug seeking habits and their maintenance in the face of negative consequences, the hallmark of addiction. I will then use causal genetic manipulations to test the hypothesis that IL long term changes in the expression of the GluA2 AMPA glutamate receptor subunit in the amygdala nuclei
contribute to the establishment and maintenance of aDLS dopamine dependent control over behaviour. I will also determine wether GluA2 contributes to the control exerted by the IL over the amygdala. Lastly, I expect that GluA2 levels play a crucial role in effecting a shift of processing within the amygdala and thus a shift to persistent cocaine-seeking habits. These results would advance our understanding of addiction and offer insights into the role of glutamate on a
behavioural, circuits, and cellular level, potentially providing new targets for treatment. My hypothesis is that ILC projections to the amygdala drive the functional transitions from BLA to
CeN in the control over aDLS-dopamine dependent mechanisms that support compulsive drug seeking habits and that this shift is dependent on GluA2-mediated plasticity.
I now propose to define the underlying neural circuitry by using fibre photometry in behaving rats, increasing evidence suggests that drug addiction stems from loss of control over maladaptive
habits. At the neural system levels, the instantiation of drug seeking habits has been shown to be dependent on functional transitions in the amygdala driving functional transitions in the striatum.
My research will aim to illuminate the cortico-amygdalo-striatal circuits that support these functional transitions underlying the development of maladaptive drug seeking habits in the rat. More precisely, I will seek to test the hypothesis that the infralimbic (IL) cortex controls the functional shift from the basolateral to the central nucleus of the amygdala that is involved in the recruitment and maintenance, respectively, of dorsolateral striatum dopamine dependent drug
seeking habits. In order to achieve this, I will deploy an array of contemporary neuroscience techniques, such as fibre photometry, optogenetics and RNAscope combined with novel models of compulsive drug seeking habits in the rat to to identify the contribution of cortico-amygdala circuits and underlying cellular and molecular mechanisms to the the development of drug seeking habits and their maintenance in the face of negative consequences, the hallmark of addiction. I will then use causal genetic manipulations to test the hypothesis that IL long term changes in the expression of the GluA2 AMPA glutamate receptor subunit in the amygdala nuclei
contribute to the establishment and maintenance of aDLS dopamine dependent control over behaviour. I will also determine wether GluA2 contributes to the control exerted by the IL over the amygdala.