Study of the role of glutamatergic pathways from the anterior cingulate cortex on nitrergic mechanisms of the ventromedial hypothalamus and periaqueductal grey matter involved in the genesis of defensive responses evoked in mice threatened by snakes

Abstract

The cortex of the rostromedial region of the frontal lobe, which is known as medial prefrontal cortex (MPFC), has been implicated in the modulation of fear-related defensive responses organised by subcortical structures. Recent studies have shown that the anterior cingulate cortex (ACC), a structure that also integrates the MPFC, has glutamatergic efferences that play a relevant role in the regulation of defensive behaviours and fear-induced antinociception, organised by neurons of both the anterior and posterior hypothalamus. However, there is a lack of studies showing the participation of ACC in the control of these defensive responses organised by neurons of the medial zone of the hypothalamus, especially those located in the dorsomedial division of the ventromedial hypothalamus (dmVMH), as well as neurons of the midbrain, such as those of periaqueductal grey matter (PAG), one of the main structures of the midbrain involved in the genesis of defensive reactions and nociceptive control. To investigate this cortical modulation of defensive behaviour, morphological techniques will be used to map the existence of glutamatergic pathways that connect ACC to the dmVMH and PAG. In addition, pharmacological approaches will focus on the influence of glutamatergic pathways of ACC on dmVMH and PAG nitrergic activity in fear-induced antinociception and defensive reactions will be investigated. The hypothesis of this work is that ACC glutamatergic pathways regulate nitrergic activity in dmVMH and PAG, involved in the genesis of panic-like defensive reactions and unconditioned fear-induced antinociception.