In the same Dolutegravir purchase chronic stress models that lead to amygdala neuronal hypertrophy and shrinkage of dendrites in hippocampus, there is shrinkage of dendrites and loss of spines throughout the medial prefrontal cortex while dendrites expand in the orbitofrontal cortex (OFC) (Liston et al., 2006). Because the OFC is involved in determining the saliency of reward or punishment (Schoenbaum and Roesch, 2005), this may reinforce the changes in the basolateral amygdala. For the medial prefrontal cortex, stress-induced impairment has been linked to poor cognitive flexibility

in both animal and human studies (Dias-Ferreira et al., 2009, Liston et al., 2009 and Liston et al., 2006). Moreover, circadian disruption impairs cognitive flexibility and causes shrinkage of medial prefrontal cortical dendrites

(Karatsoreos et al., 2011). The mechanism for medial PFC dendritic remodeling is likely to involve the same mechanisms as those in the hippocampus, namely, excitatory amino acids and glucocorticoids Dinaciclib mw (Cerqueira et al., 2005 and Martin and Wellman, 2011). The structural changes are largely reversible in healthy young animals after the termination of stress. See Box 3. When the stress is over, remodeled brain circuits recover at least in younger animals with healthy brain architecture (Bloss et al., 2010 and Radley et al., 2005), but there are clues that the recovered state is not the same as the initial state. For example, in the studies of recovery from chronic stress in the medial prefrontal cortex of young adult rats, the retraction of apical dendrites during chronic stress was from distal dendrites and the re-growth of those dendrites during recovery was from the more proximal dendrites (Fig. 1) (Goldwater et al., 2009). Yet there was reversal of deficits in D1 receptor expression and recovered function in terms of dopamine enhanced LTP during recovery from chronic stress, and it is not yet clear if the differences in dendritic

retraction and regrowth reflect any reorganization of neuroanatomical circuitry (Goldwater et al., 2009). This apparent reversibility hides the fact that genomic responses to stressors are dependent on the stress-history of the individual, as will through be elaborated below. Moreover, there is clearly loss of reversibility in aging (Bloss et al., 2010) and also a failure to show plasticity in response to stress as a result of maternal separation stress in infancy (Eiland and McEwen, 2012) and haploinsufficiency (Magarinos et al., 2011) or overexpression (Govindarajan et al., 2006) of brain derived neurotrophic factor (BDNF). Box 3 The young adult human prefrontal cortex reflects the effects of chronic stress by showing impaired cognitive flexibility and reduced functional connectivity that parallels the effects of stress in the young adult rat brain, including the reversibility after the end of the stressful period (Bloss et al., 2010, Liston et al.