The amygdala plays a critical role in processing affective stimuli. In humans, imaging studies suggest that reciprocal interactions between the amygdala and prefrontal cortex (PFC) may be associated with cortical control of affect. Significantly, only the basolateral nucleus of the amygdala (BLA) has marked reciprocal connections with the PFC, and in response to affective stimuli firing activity in the BLA precedes firing activity in the PFC. Moreover, during fear conditioning, firing activity in neurons of the BLA and PFC becomes synchronized. Synchronized oscillations in neural networks are thought to represent a """"""""binding"""""""" mechanism that rapidly links spatially distant structures, and it is our contention that synchronized activity in the BLA and PFC provides a mechanism by which the emotional valence of sensory stimuli can be rapidly evaluated. Abnormal cortical synchrony has been observed in schizophrenia, autism, PTSD and depression. In order to understand the role of abnormal synchrony in the etiology of affective disorders, we must first understand how synchronized activity normally develops in areas like the BLA. However, little is known of the processes by which the activity of local ensembles of BLA projection neurons (PNs) may become synchronized, let alone how phase synchrony is achieved between the BLA and PFC. We will directly address this knowledge gap by systematically examining the physiological and neuroanatomical substrates that contribute to oscillatory and synchronous activity in BLA PNs. More specifically, we will test the hypothesis that: a) intrinsic membrane currents endow BLA PNs with a """"""""resonant frequency"""""""" that predisposes the neurons to fire rhythmically at membrane potentials close to action potential threshold, and b) that these PNs, along with BLA interneurons (INs), are embedded in a structurally organized intrinsic neural network that facilitates synchronous activation of groups of PNs. A combination of electrophysiological and anatomical approaches will be used to test this hypothesis including: 1. Characterize and contrast the physiological and neuroanatomical properties contributing to oscillatory activity in PNs of the magnocellular and parvicellular subdivisions of the BLA. 2. Characterize the intrinsic network connectivity of the rat BLA using dual cell recording to show synchronous activity in PN-PN interactions, and PN-IN interactions. 3. Characterize the physiological properties of BLA PNs that project to the prefrontal cortex in rat and primate. By clarifying the role of intrinsic microcircuits of the BLA in generating synchronized oscillatory activity and its relationship with the PFC, these studies will be critical in furthering our understanding of affective disorders and in developing novel therapeutic treatment strategies.
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