Dysfunction of the glutamate system is increasingly considered a core feature of stress-dependent neuropsychiatric disorders. Clinical neuroimaging studies have shown consistent volumetric changes in limbic and cortical areas, while preclinical studies with stress protocols in rodents found dendritic remodeling and reduction of synapses in the same areas, suggesting that destabilization of glutamate release/transmission, in turn induced by stress and glucocorticoids, is crucial for cognitive function and neural architecture. We found that acute stress rapidly enhances depolarization-evoked glutamate release/transmission in prefrontal and frontal cortex (PFC/FC), an effect mediated by stimulation of synaptic corticosterone receptors. Corticosterone rapidly increases the readily releasable pool of glutamate vesicles, through activation of synaptic receptor-mediated nongenomic mechanisms in PFC/FC. Moreover, we have shown that chronic antidepressants are able to prevent the enhancement of glutamate release induced by acute stressors in these areas.
Musazzi, L., Treccani, G., Perego, C., Nava, N., Nyengaard, J., Popoli, M. (2014). Synaptic Stress, Changes in Glutamate Transmission and Circuitry, and Psychopathology. In Synaptic stress and pathogenesis of neuropsychiatric disorders (pp. 33-52). Springer New York [10.1007/978-1-4939-1056-4_3].
Synaptic Stress, Changes in Glutamate Transmission and Circuitry, and Psychopathology
L. Musazzi;
2014
Abstract
Dysfunction of the glutamate system is increasingly considered a core feature of stress-dependent neuropsychiatric disorders. Clinical neuroimaging studies have shown consistent volumetric changes in limbic and cortical areas, while preclinical studies with stress protocols in rodents found dendritic remodeling and reduction of synapses in the same areas, suggesting that destabilization of glutamate release/transmission, in turn induced by stress and glucocorticoids, is crucial for cognitive function and neural architecture. We found that acute stress rapidly enhances depolarization-evoked glutamate release/transmission in prefrontal and frontal cortex (PFC/FC), an effect mediated by stimulation of synaptic corticosterone receptors. Corticosterone rapidly increases the readily releasable pool of glutamate vesicles, through activation of synaptic receptor-mediated nongenomic mechanisms in PFC/FC. Moreover, we have shown that chronic antidepressants are able to prevent the enhancement of glutamate release induced by acute stressors in these areas.
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