Optogenetic dissection of medial prefrontal cortex circuitry

Abstract

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats

“…Interestingly, parkinsonian patients also exhibit this dissociation of symptoms of anhedonia and depression [31,32]. Since 6-OHDA triggers functional alterations in the striatum [33,34] as well as in the PFC [35,36] and these two interconnected brain regions [37,38] are involved in the control of motivation, reward, and defense behaviors relevant to depression [reviewed in [39][40][41][42], we explored neurochemical and electrophysiological alterations in these two brain regions at 7 and at 21 days after 6-OHDA administration to gain a mechanistic insight on this temporal dissociation between anhedonia and defense behaviors relevant to depression. We observed that the appearance of anhedonia at 7 days was selectively associated with an increased density of both D 1 and D 2 receptors in the striatum, together with a decreased short-term plasticity and increased dopaminergic sensitivity in corticostriatal synapses.…”

The Human BNST: Functional Role in Anxiety and Addiction

“…In the first study, Kinnison et al (2012) showed increased BNST functional connectivity with both the anterior insula and dorsomedial PFC during threat of shock. The anterior insula and dorsomedial PFC have known functional roles in threat processing and anxiety responses and are prominent members of the neural salience network (Downar et al, 2002;Eickhoff et al, 2014); these regions likely interact with the BNST to express an aversive emotional state during anticipation of threat (Drabant et al, 2011;Klumpers et al, 2014;Mechias et al, 2010;Riga et al, 2014). In a second study, McMenamin et al (2014) showed that the BNST had more functional interactions with its surrounding network during threat of shock, but only for the most anxious participants.…”

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

“…Some human neuroimaging studies have suggested that alcohol-dependence and chronic pain may also share mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions [2]. The mPFC, a cortical structure that includes the prelimbic (PrLC), infralimbic (ILC), and anterior cingulate cortex (ACC) [4][5][6], has been demonstrated to be involved in pain processing [7][8][9][10][11][12][13][14]. More recently, we also demonstrated that the mPFC is involved in the mediation of empathy for pain in rats, a phenomenon in which the mechanical pain sensitivity and spinal nociceptive responses of rats are dramatically increased after social interaction with a cagemate (but not a non-cagemate) in pain [15].…”