Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval

2,5-Dihydro-2,4,5-Trimethylthiazoline (TMT)-Induced Neuronal Activation Pattern and Behavioral Fear Response in GAD67 Mice

“…These innate evolutionary conserved fear pathways seem to include strongly connected limbic structure like the MeA and the BNST that both receive direct olfactory information and send projections to the PVN and brain stem structures allowing rapid activation of the HPA stress axis and immediate initiation of behavioral reactions after perception of predator odor for outliving the situation. Present and prior data of our group as well as results of other investigators indicate an important role of the BNST for innate fear responses to TMT [5] [24] [32] [35] [55] [56]. Since, pharmacological inhibition of the BNST (but not the amygdala) by the GABA-A receptor agonist muscimol was shown to disrupt fear responses to TMT [32] [54], and since, increased anxiety levels were reported after inactivation of GABA synthesis within the BNST [59], it can be assumed that GABAergic mechanisms in the BNST are involved in TMT-induced innate fear responses.…”

“…The BNST in turn was thought to stimulate the hypothalamic-pituitary-adrenal (HPA) axis [35]. Contrary to the established role of the BNST for unconditioned innate fear, the CeA is a region accepted as central for conditioned fear [5] [54]- [56]. Therefore, present results indicating significant TMT-induced neuronal activation of the CeA appear to be in conflict with this suggestion and with data demonstrating that inactivation of the CeA is ineffective in attenuating unconditioned freezing behavior to TMT [32].…”

“…Since, the BNST is the most popular TMT-activated brain region in mice [5] [19] [56], and BNST neurons are regulated by an extensive network of GABAergic neurons [56] [59] [60] [63], such a research seems to be interesting.…”

Chronic intermittent ethanol and acute stress similarly modulate BNST CRF neuron activity via noradrenergic signaling

“…A number of previous studies suggested that a variety of stressors and drugs of abuse enhance neuronal activity in the BNST in general as well as enhance the activity of BNST CRF neurons specifically (Casada and Dafny 1991;Funk et al 2006;Janitzky et al 2014;Tran et al 2012;Walker et al 2009). Previous data also indicate that CRF signaling may be an important factor in overall BNST excitability and that BNST CRF neurons are sensitive to β-AR stimulation.…”

“…In particular, corticotropin releasing factor (CRF) signaling is thought to be an important regulator of pro-anxiety BNST-mediated responses to stress (Ciccocioppo et al 2003;Koob 1999;Sink et al 2013;Walker et al 2009). Numerous studies have shown that CRF signaling is enhanced in the BNST following acute and chronic stress exposures (Choi et al 2006;Funk et al 2006;Janitzky et al 2014;Tran et al 2012). In addition, a number of studies indicate that stress or adverse external stimuli can increase norepinephrine (NE) release in the BNST (Flavin and Winder 2013;Fuentealba et al 2000;Pacak et al 1995;Park et al 2012).…”