Figure 4
Schematic representation of the different levels that anchor the transition from a healthy to a stressed neuromatrix. (a) At the molecular and synaptic level, there is growing evidence that stress has a dual effect on the glutamatergic transmission in prefrontal cortex (PFC) pyramidal neurons: on one hand, acute stress, by activating glucocorticoid receptors (GRs), increases serum-and-glucocorticoid-inducible kinase (SGK) and Rab4 that augments the trafficking and function of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and leads to potentiated synaptic transmission; on the other, chronic stress reduces AMPA and NMDA receptor expression and synaptic transmission through the enhancement of ubiquitin/proteasome-mediated degradation of some of its subunits (GluR1 and NR1), a process that is under the control of the E3 ubiquitin ligase Nedd4-1 and Fbx2, respectively. (b) At the neuroanatomical level, the progressive exposure to stress triggers a morphological reorganization of dendritic arbors and spines; as an example of the complexity of the structural reorganization, although in the dorsal hippocampus chronic stress induces an atrophy of apical dendrites in CA3 pyramids, the opposite occurs in the ventral hippocampus. (c) At the functional level, an example of a power spectral density map in ventral hippocampus of controls (healthy), acute stressed (acute) and chronic unpredictable stressed (chronic) rats for delta (1–4 Hz), theta (4–12 Hz) and low gamma (20–40 Hz) frequency bands showing that exposure to stress progressively increases power in this brain node. At the behavioral level, an example of progressive spatial working memory deficits from a healthy condition to a chronic stressed state. (a) Is an illustration of results presented in refs. 134, 170, (b) in refs. 87, 89 and (c) in refs. 98, 109.
