Stress acuto, ketamina e trasmissione sinaptica nella mPFC di ratto adulto

Stress is the physiological response to hostile situations, that can result in maladaptive mechanisms and became a potential risk factor for many neuropsychiatric disorders, even after a single exposure to stressor. The mPFC plays a central role in the regulation of the stress response. Stress modifies the Glu transmission in this area, e.g. in acute foot-shock (FS) stress models, an increase in depolarizationevoked Glu release from synaptosomes was shown 1 day and 1 hour after stress exposure. 1 day after, there is also an increase in the number of synapses and a decreased development of the dendritic arbour of principal, similarly to what happens in chronically stressed animals. The work described in this thesis aims to investigate the time course of the effects of acute stress, FS protocol, on excitatory synaptic transmission of neurons in cortical layers 2/3 (L2-3) and 5 (L5) in the prelimbic area of the mPFC of adult rats. Likewise, investigating the possible use of ketamine at low doses for the rescue of FS effects on synaptic transmission, as suggested by the involvement of mPFC in the antidepressant action of this treatment. Using the whole-cell patch-clamp technique, we recorded spontaneous and miniature excitatory transmission, in both L2-3 an L5. The same technique was used to record spontaneous excitatory and inhibitory current in L2-3 to estimate the E/I ratio. Our data confirm an early FS stress-induced enhancement of Glu transmission in L2-3, linked to the activation of a few strong synapses, and not paralleled by an increase in the E/I ratio in single neurons. On the contrary, 1 day after FS, the excitatory Glu conductance is increased in parallel with an increase in the E/I balance. Ketamine at this time increases the frequency of sEPSCs.