Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

Abstract

The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms.

Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats

“…sIPSC/sEPSC frequency, amplitude, area, decay time) in BLA pyramidal neurons did not differ between adolescents and adults, consistent with the notion that both GABA and glutamate systems are stable after P28 (Ehrlich et al, 2013; Ehrlich et al, 2012) and previous comparisons of adolescents and adults (Zhang and Rosenkranz, 2016). However, we observed a very strong trend toward an increase in the membrane resistance of adult BLA pyramidal neurons in adolescents only when using a K-gluconate internal solution – a common solution used to record glutamate-mediated neurotransmission – but not with a KCl internal solution.…”

Stress Accelerates Defensive Responses to Looming in Mice and Involves a Locus Coeruleus-Superior Colliculus Projection

“…Our accelerated looming-evoked defensive responsive results are in line with this affective modulation of the looming responses in humans. Previous reports have demonstrated the impact of stress in anxiety and paralleled conditioned fear responses [28][29][30][31][32][33] and the impact of anxiogenic manipulations in ultrasound-evoked defensive behaviors [34]. To our best knowledge, we report here the first neuronal pathway that is involved in regulating the impact of stress on innate visual-cue-induced defensive fear responses.…”

Sex- and Estrus-Dependent Differences in Rat Basolateral Amygdala

“…A handful of studies demonstrate sex differences of human amygdala activation, including three meta-analyses of the response to facial expressions (Sergerie et al, 2008;Fusar-Poli et al, 2009;Filkowski et al, 2017). Several studies have found sex differences in the laterality of amygdala activation (Cahill et al, 2004) or functional connectivity to other brain regions Engman et al, 2016;Wu et al, 2016), while others find greater amygdala activation in men in response to positive valenced and sexual stimuli (Hamann et al, 2004;Stevens and Hamann, 2012) but greater amygdala activation in women in response to negative valenced stimuli (Wrase et al, 2003;Hofer et al, 2006;Stevens and Hamann, 2012;Mareckova et al, 2016) or during non-emotion-related tasks (Hill et al, 2014), despite evidence of similar anatomical size (Marwha et al, 2017). Furthermore, major affective disorders that are more common in women (e.g., depression, anxiety, post-traumatic stress disorder) are associated with hyperactivation of the BLA (Sheline et al, 2001;Etkin and Wager, 2007;Victor et al, 2010;Hattingh et al, 2012;Sartory et al, 2013).…”