, 2009a). Facilitated by the rapid, chaperone-mediated recycling of nuclear GRs, ultradian gene pulses trigger Vismodegib cost changes in GR-regulated promoter activity that are tightly coupled to physiological oscillations (Stavreva et al., 2009a). Ultradian glucocorticoid oscillations penetrate the blood/brain barrier and are preserved within stress-sensitive brain areas (Droste et al., 2008), where they probably play an important role in responding to stressors and other environmental stimuli in physiological circumstances. Conversely,

in chronic stress models, disruptions of the ultradian oscillation alter gene expression responses in these regions and cause correlated changes in locomotor activity and risk assessment behaviors (Sarabdjitsingh et al., 2010a and Sarabdjitsingh et al., 2010b). Whether and how these ultradian oscillations affect synaptic remodeling remains unclear, but they are likely to have

important effects, acting Selleckchem Y-27632 potentially through both transcriptional and non-transcriptional mechanisms (McEwen, 1991, Makara and Haller, 2001, Lösel and Wehling, 2003 and Groeneweg et al., 2011). As mentioned above, glucocorticoids can increase spine formation in cortical pyramidal cells by ten-fold in just 20 min, acting through non-genomic signaling pathways (Liston et al., 2013). Similarly, glucocorticoids can rapidly enhance the frequency of miniature excitatory postsynaptic potentials, increasing glutamate release probability by activating a non-genomic, MR-dependent signaling pathway (Karst et al., 2005). Similarly rapid effects have been observed in other studies in the prefrontal cortex, hippocampus, amygdala, and hypothalamus (Di et al., 2003, Groeneweg et al., 2011, Popoli et al., 2011 and Tasker and Herman, 2011). The studies reviewed above indicate

that stress and glucocorticoids have potent but complex effects on synaptic remodeling, and understanding the underlying molecular mechanisms is a rapidly emerging area of active investigation. These studies are challenging due in part to the fact that stress effects on dendritic Rutecarpine remodeling, synaptic plasticity, and associated molecular signaling mechanisms vary with the region and developmental age under investigation (Lupien et al., 2009). However, one theme to emerge from this work is that glucocorticoids may engage distinct intracellular signaling mechanisms, depending on the timing of a stressor and the kinetics of the glucocorticoid response. For example, in response to an acute stressor, glucocorticoids promote memory consolidation and impair working memory (McGaugh and Roozendaal, 2002 and Barsegyan et al., 2010) through a mechanism involving beta adrenergic- and cAMP-dependent activation of protein kinase A in the amygdala and prefrontal cortex (Roozendaal et al., 2002 and Barsegyan et al., 2010).