Dopamine and Cannabinoid Modulation of Emotional Memory in the Mesocorticolimbic System

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To make sense of the world around us, the brain must constantly filter incoming sensory information and accurately interpret the emotional significance and relevance of these inputs. Of equal importance, the brain must form appropriate associative memories between the meaning of specific environmental cues and their emotional salience in order to respond appropriately to incoming sensory information and guide future behavioural responses. Two neurochemical substrates that are known to regulate affective states and associative memory formation are the brain's dopamine (DA) and cannabinoid receptor systems. These systems not only functionally interact with one another, but are localized in brain regions that are critical for emotional processing. In the mammalian brain, the basolateral amygdala (BLA), ventral hippocampus (vHIPP) and medial prefrontal cortex (mPFC) form an interconnected network that regulates emotional learning and memory formation through interactions with the mesolimbic dopamine (DA) pathway, comprising the ventral tegmental area (VTA) and nucleus accumbens (NAc). These neural regions are functionally interconnected and contain high concentrations of cannabinoid and dopamine (DA) receptors, two neurotransmitter systems that are critical in the processing of emotional processing and learning. The involvement of these neurochemical pathways in emotional processing extends to both positive rewarding experiences as well as aversive events. Using a series of in vivo electrophysiological, neuropharmacological and behavioral investigative tools, our research program is exploring how these systems functionally interact in these processes and how signaling through DA and cannabinoid receptor systems may modulate the functional integration of emotional sensory processing and associative learning.***The primary goal of our research project involves the neurophysiological, behavioural and neurochemical characterization of neural mechanisms involved in the processing of emotionally salient sensory information and how signaling through these systems may control how we perceive the emotional valence (rewarding or aversive) of sensory experiences and how we form appropriate associative memories between these affective experiences and related environmental cues. Using in vivo electrophysiological associative conditioning and neural plasticity recording procedures, we are examining emotional associative learning and memory formation within single neurons of the rodent brain and at the behavioural levels, by examining associative neuronal responses to sensory cues that have been paired with either aversive (footshock) or rewarding (e.g. opiates) stimuli. Our studies aim to reveal critical new insights into how the brains cannabinoid system may control emotional processing through functional interactions with the brain's dopamine system.***********