Short environmental enrichment in adulthood reverses anxiety and basolateral amygdala hypertrophy induced by maternal separation

Abstract

Maternal separation during early childhood results in greater sensitivity to stressors later in adult life. This is reflected as greater propensity to develop stress-related disorders in humans and animal models, including anxiety and depression. Environmental enrichment (EE) reverses some of the damaging effects of maternal separation in rodent models when provided during peripubescent life, temporally proximal to the separation. It is presently unknown if EE provided outside this critical window can still rescue separation-induced anxiety and neural plasticity. In this report we use a rat model to demonstrate that a single short episode of EE in adulthood reduced anxiety-like behaviour in maternally separated rats. We further show that maternal separation resulted in hypertrophy of dendrites and increase in spine density of basolateral amygdala neurons in adulthood, long after initial stress treatment. This is congruent with prior observations showing centrality of basolateral amygdala hypertrophy in anxiety induced by stress during adulthood. In line with the ability of the adult enrichment to rescue stress-induced anxiety, we show that enrichment renormalized stress-induced structural expansion of the amygdala neurons. These observations argue that behavioural plasticity induced by early adversity can be rescued by environmental interventions much later in life, likely mediated by ameliorating effects of enrichment on basolateral amygdala plasticity.

Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress

“…In our experiment, the potentiated corticosterone increase of MS/SH rats in response to an acute stressor (i.e., cage rotation) was not associated with elevated basal corticosterone in MS/SH compared to NMS/SH groups. This finding is in accordance with studies reporting no differences in basal concentrations in animals previously exposed to early‐life stress (Knuth and Etgen, 2007; Koe et al, 2016; Rüedi‐Bettschen et al, 2005; Slotten et al, 2006; Wigger and Neumann, 1999). Given the significant role of the hippocampus, particularly its glucocorticoid receptor (GR) system, in the HPA negative feedback mechanism, it may be suggested that hippocampal alterations may be associated with the potentiated stress response.…”

Early life stress and later peer distress on depressive behavior in adolescent female rats: Effects of a novel intervention on GABA and D2 receptors

“…The LH paradigm used in this study consisted of the following conditions: 1) an escapable shock (ES) subject and 2) a no shock or “naïve to aversive stimuli” group (NS), where these animals were exposed to, but did not directly experience shock on the first day. Each LH condition assesses different aspects of depressive-like behavior via separate neuronal circuitry [28, 36]. Our previous studies found that females exposed to MS exhibited increased escape latency in the NS group only [26], an LH condition associated with motivational circuitry [26, 40, 41].…”

“…MS is associated with changes in GABA in the prefrontal cortex (PFC [22-24]) and the amygdala [25]. Rats with a history of MS show changes in PFC-mediated behaviors including learned helplessness (LH), working memory deficits, depressive-like behavior, and reduced social interaction [24, 26-28]. Prior studies show reduced GABAergic calcium-binding protein parvalbumin (PVB) expression in MS adolescent males [24] and females [26] and the basolateral amygdale in MS (BLA; [22, 23]).…”

Aberrant H3.3 dynamics in NAc promote vulnerability to depressive-like behavior

“…Next, to examine if positive life experiences may result in opposing patterns of H3.3 dynamics in NAc, we used an EE paradigm that has previously been shown to promote enhanced synaptic plasticity and cognition and can prevent or reverse some aspects of depressive-like behaviors, such as anhedonia and anxiety (16)(17)(18). We observed that EE results in a significant down-regulation of H3f3b, but not of H3f3a, expression in mouse NAc (Fig.…”