The hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.

Monocular deprivation early in postnatal development leads to anatomical and physiological changes in the lateral geniculate nucleus (LGN) and visual cortex. Many of these changes are dependent upon activation of the NMDA receptor. We have examined the role of visual experience in modifying NMDAR1 subunit expression in the LGN of animals reared with various forms of visual deprivation. Following monocular deprivation initiated either at eye opening or at the peak of the critical period, there were approximately 20% fewer NMDAR1-immunopositive neurons in the deprived laminae of the LGN. The loss of NMDAR1-immunopositive neurons was found throughout both the binocular and monocular segments of the LGN and after monocular deprivation until just 3 weeks of age. These results indicate that the loss of NMDAR1 in the LGN following monocular deprivation does not simply reflect changes in the visual cortex. The loss of NMDAR1 expression was not necessarily permanent. Initiation of binocular vision at the peak of the critical period ameliorated the effect of monocular deprivation and the introduction of a period of reverse occlusion led to a complete reversal. Taken together, the results show that the expression of the NMDAR1 subunit in the LGN can be modified by the pattern of visual experience during postnatal development.

Electrophysiological and pharmacological experiments suggest the presence of an electrogenic glutamate transporter in the motornervous system of the parasitic nematode Ascaris suum. This putative transporter occurs in hypodermis (a tissue in some respects analogous to glia) and in DE2 motorneurons, a dorsal excitatory motorneuron class which receives excitatory glutamatergic post-synaptic potentials. Glutamate application to hypodermis produced non-conductance mediated depolarizations that were smaller in amplitude and slower in rate of rise than DE2 responses where a glutamate-activated conductance occurs. The hypodermal response is sodium dependent and calcium independent. Excitatory amino acid ionotropic receptor agonists (kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid and N-methyl-D-aspartate) were ineffective in eliciting hypodermal responses. The ionotropic receptor antagonist, 6,7-dinitroquinoline-2,3-dione, had no effect on hypodermal glutamate responses. The L- and D-forms of glutamate, aspartate and homocysteate produced hypodermal and DE2 depolarizations consistent with the pharmacological profile for glutamate transporters in other systems. Glutamate transport inhibitors (L-trans-pyrrolidine-2,4-dicarboxylate and beta-hydroxyaspartate) elicited electrogenic depolarizations in hypodermis and DE2. These results suggest that the hypodermal glutamate response has an electrogenic transporter component, while the DE2 response has 2 components, one conductance-mediated and the other due to an electrogenic transporter.