Amygdaloid involvement in the defensive behavior of mice exposed to the open elevated plus-maze

Abstract

Previous studies have shown that the exposure to an open elevated plus maze (oEPM, an EPM with all four open arms) elicits fear/anxiety-related responses in laboratory rodents. However, very little is known about the underlying neural substrates of these defensive behaviors. Accordingly, the present study investigated the effects of chemical inactivation of the amygdala [through local injection of cobalt chloride (CoCl: a nonspecific synaptic blocker)] on the behavior of oEPM-exposed mice. In a second experiment, the pattern of activation of the basolateral (BLA) and central (CeA) nuclei of the amygdala was assessed through quantification of Fos protein expression in mice subjected to one of several behavioral manipulations. To avoid the confound of acute handling stress, 4 independent groups of mice were habituated daily for 10days to an enclosed EPM (eEPM) and, on day 11 prior to immunohistochemistry, were either taken directly from their home cage (control) or individually exposed for 10min to a new clean holding cage (novelty), an eEPM, or the oEPM. An additional group of mice (maze-naïve) was not subjected to either the habituation or exposure phase but were simply chosen at random from their home cages to undergo an identical immunohistochemistry procedure. Results showed that amygdala inactivation produced an anxiolytic-like profile comprising reductions in time spent in the proximal portions of the open arms and total stretched attend postures (SAP) as well as increases in time spent in the distal portions of the open arms and total head-dipping. Moreover, Fos-positive labeled cells were bilaterally increased in the amygdaloid complex, particularly in the BLA, of oEPM-exposed animals compared to all other groups. These results suggest that the amygdala (in particular, its BLA nucleus) plays a key role in the modulation of defensive behaviors in oEPM-exposed mice.

Survival circuits and risk assessment

“…In addition to the lateral hypothalamus [37], the posterior hypothalamus may be involved in RA (in the form of novel object exploration) and may concurrently control the anxiety-related neuroendocrine stress response [38]. Consistent with the top-down control of the PAG by the amygdala in relation to freezing and flight, the basolateral amygdala appears to be involved in the generation of RA as measured by stretch-attend in the elevated plus-maze [39] and by the firing of one group of its cells during periods of hesitation or retreat, but not of escape [40*].…”

Maternal deprivation alters nociceptive response in a gender‐dependent manner in rats

“…In addition, in the present study, we showed that male animals presented a lower numbers of PHD and higher NPHD movements in relation to female (at the same age), indicating an effect of gender in these parameters. This result can be related to an increase in both exploratory behavior and risk assessment, as well as a decrease in anxiety‐like behaviors (Sorregotti et al, 2018). In contrast, female rats showed lower latency time to start exploring the apparatus, and there was an interaction between gender and maternal deprivation on the rearing behavior at P42.…”

How much fear is in anxiety?

“…Previous studies investigating the neuropharmacological basis of altered open-arm avoidance of inbred mouse strains using the EPM, report a consistent dose-dependent anxiolytic effect of systemically administered benzodiazepines ( Rodgers et al, 1992; Cole and Rodgers, 1995; Holmes and Rodgers, 1999; Griebel et al, 2000 ) which emphasizes the predictive validity of this testing situation. More recent studies which assess the involvement of specific brain areas in the expression and regulation of open-arm avoidance in rats and mice implicate the prefrontal cortex (PFC) ( Adhikari et al, 2010,2011; Kumar etal., 2013 ), bed nucleus of the stria terminalis(BNST) ( Kim etal., 2013 ), lateral septum (LS) to anterior hypothalamic area (AHA) projection ( Anthony et al, 2014 ), medial septum (MS) ( Shin et al, 2009; Zhang et al, 2017 ), septo-habenular pathway ( Yamaguchi et al, 2013 ), basolateral amygdala (BLA) ( Sorregotti et al, 2018 ) and specifically its projections towards the central nucleus of the amygdala (CeA) ( Tye et al, 2011 ) and ventral hippocampus (vHPC) ( Felix-Ortiz et al, 2013 ) and PFC ( Felix-Ortiz et al, 2016 ), vHPC to PFC projection ( Padilla-Coreano et al, 2016 ), vHPC-lateral hypothalamic area (LHA) projection ( Jimenez et al, 2018 ), habenula (Hb) ( Pang et al, 2016 ), interpeduncular nucleus (IPN) ( Zhao-Shea et al, 2015 ), laterodorsal tegmentum (LdT) ( Yang et al, 2016 ) but also the PAG ( Santos et al, 2003; Netto and Guimarães, 2004; Borelli and Brandão, 2008; Lima et al, 2008; Campos and Guimarães, 2009; Mendes-Gomes and Nunes-de Souza, 2009; Terzian et al, 2009; Muthuraju et al, 2016 ) and the SC ( Muthuraju et al, 2016 ). It is clear that all these brain structures cannot mediate the same types and aspects of avoidance behavior (e.g.…”