The rostromedial region of the frontal lobe cortex (mPFC; medial prefrontal cortex) has been implicated in the modulation of fear- and anxiety-related defensive responses, organised in diencephalic and mesencephalic structures. Recent studies have shown that the anterior cingulate cortex (ACC), a structure that also integrates the mPFC, has glutamatergic neurons that play a relevant role in the regulation of defensive behaviours and fear-induced antinociception, organised by anterior and posterior hypothalamic neurons. In addition, data referring to the postdoctoral internship, but not yet published, suggest that ACC activation with NMDA, an excitatory amino acid, appears to modulate defensive responses organised by dorsomedial division of the ventromedial hypothalamus (dmVMH) and dorsal periaqueductal gray matter (dPAG) neurons. However, for the modulatory role of ACC on nociceptive processes we hypothesize that the ACC glutamatergic pathways recruit dmHMH and dPAG as relays before reaching the dorsal horn of the spinal cord (DHSC), but it remains unclear. Thus, to better understand the role of both dmVMH and dPAG in CCA-mediated nociceptive processes, electrophysiological techniques combined with pharmacological approaches will be performed in our study. Male C57/BL6 mice, anesthetised, and exposed to heat stimulation in the paw, will be subjected to electrophysiological recordings in the DHSC to record the activity of local nociceptive neurons, after chemical stimulation of ACC with NMDA, preceded by microinjections of either lidocaine or LY235959, a NMDA receptor antagonist, in the dmVMH and dPAG.
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