Stressor controllability and Fos expression in stress regulatory regions in mice

Abstract

Controllability is an important determinant of the effects of stress on behavior. We trained mice with escapable (ES) and inescapable (IS) shock and examined behavioral freezing and Fos expression in brain regions involved in stress to determine whether stressor controllability produced differential activation of these regions. Mice (C57BL/6J) were trained to escape footshock by moving to a safe chamber in a shuttlebox. This terminated shock for both ES mice (n=5) and yoked-control mice receiving IS (n=5). Handling control (HC) mice (n=5) experienced the shuttlebox, but never received footshock. Training took place on three days (20 trials per day, 0.2 mA, 5.0 sec maximum duration, 1.0 min interstimulus interval). On day 3, the animals were killed two h after training and the brains were processed for Fos expression in the amygdala, hypothalamic paraventricular nucleus (PVN), laterodorsal tegmental nucleus, locus coeruleus and dorsal raphe nucleus. Fos expression after IS was greater than after ES and HC in all regions (p < .05). Fos expression after ES was greater than HC only in PVN (p < .05). Freezing in ES mice was equal to or greater than in IS mice whereas HC mice showed minimal freezing. Differential activation of brain regions implicated in stress may, in part, account for differences in behavior in the aftermath of uncontrollable and controllable stress.

Brief Optogenetic Inhibition of the Basolateral Amygdala (BLA) in Mice Alters Effects of Stressful Experiences on Rapid Eye Movement Sleep (REM)

“…Thus, our finding of an NpHR-induced increase in neuronal activity in CNA relative to that observed in the control mice is consistent with the intra-amygdaloid connectivity. CNA neurons fire in response to footshock, 57 and some, 35,58 but not all, 30 studies have reported increased c-Fos in CNA in response to conditioned stimuli. Activation of CNA appears to induce the generation of fear behavior and physiological responses via descending brain stem projections, 59 for example, electrical stimulation of CNA can promote REM in some situations whereas its inhibition suppresses REM.…”

“…29,30 Sections were labeled either with rabbit monoclonal anti-CaMKII (1:250, EP1829Y, Abcam, Cambridge, MA) or mouse monoclonal anti-GABA (1:2000, A0130, SigmaAldrich, St. Louis, MO) followed by the fluorescent secondary antibodies goat anti-rabbit Alexa Fluor 568 (1:200, Invitrogen) or goat anti-mouse Alexa Fluor 430 (1:200, Invitrogen), respectively. All blocking steps were done in PBS containing 3% normal goat serum (NGS, G9023, Sigma-Aldrich), 2% nonfat dry milk and 0.1% Triton X-100.…”

“…35,36 ) in select brain regions at 2 h post-ST. Brain regions were selected based on putative functional importance in REM regulation 30 and included the amygdala (BLA and CNA), DRN, LC, LDTg, and PPTg. We also examined the mPFC, a region involved in determining the consequences of stress and coping, and which has prominent reciprocal connections with BLA.…”

Localization of nesfatin-1 neurons in the mouse brain and functional implication

“…Such a pattern of Fos expression in the mouse brain is similar to that reported in rats exposed to WAS with Fos-immunoreactivity localized in the BNST, lateral septum, PVN, LC, dorsal raphe nucleus, VLM, NTS and lumbo-sacral spinal cord (Bonaz and Taché, 1994; Million et al, 2000). Other studies established that several stressors including restraint stress (O'Mahony et al, 2010), foot shock (Liu et al, 2009), hypertonic saline injection (Pirnik et al, 2004), ether (Korosi et al, 2005) or swim stress (Stone et al, 2007) induced Fos in stress-responsive neuronal populations in specific brain nuclei in mice namely the cingulate cortex, amygdala, PVN, Arc, paraventricular thalamic nucleus, Hi, EW, LC, dorsal raphe nucleus or VLM (Korosi et al, 2005; Liu et al, 2009; O'Mahony et al, 2010; Stone et al, 2007). …”

Neuronal NOS Inhibitor and Conventional Antidepressant Drugs Attenuate Stress-induced Fos Expression in Overlapping Brain Regions

“…In this regard, studies investigating Fos expression as a marker of neuronal activity have consistently shown that a set of structures are activated in response to the exposure to different stressors in animal models of depression, which includes the mPFC, the hippocampus, the lateral septum, the nucleus accumbens, the amygdaloid nuclei (basolateral, central and medial), the PVN, the locus coeruleus, the thalamus (mainly the paraventricular), the PAG, and the raphe nuclei [MRN and DRN;(Bilang-Bleuel et al 2002;Bruijnzeel et al 1999;Duncan et al 1993;Duncan et al 1996;Liu et al 2009;Muigg et al 2007;Ons et al 2004;Roche et al 2007;Wulsin et al 2010)]. Neuroimaging and post-mortem studies with depressed individuals have also shown significant activity and morphological changes in many of these structures [for review see (Krass et al 2011;Price and Drevets 2010)].…”