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.
Highlights
Adversity in early postnatal life has a lasting negative impact on behavioural and emotional functioning of individuals.[1,2,3] Compelling evidence suggests that rodent maternal separation (MS), widely used to mimic early-life stress in human infants, leads to hyper-reactivity of the hypothalamic − pituitary − adrenal axis in adulthood.[4,5,6] This is accompanied by anxious or depressive-like behaviour or cognitive deficits in some instances.[7,8,9,10] In addition, these effects have been suggested to be downstream of neuroplasticity alterations
A single episode of MS for 24 h at postnatal day 3 does not affect dendritic complexity in the basolateral amygdala (BLA).[21]. It is not known if repeated MS results in BLA structural plasticity in parallel to its observed potentiation of anxiety. This is an important gap in knowledge because dendritic and spine changes in the BLA are central to stress-induced anxiogenesis.[22,23,24]
Congruent to emergence latency from home cage, MS caused robust decrease in percentage open-arm entries when housed in standard conditions during adulthood (Figure 2a; Two parameters, total dendritic length and number of branch points, were quantified in 334 BLA neurons (8 − 11 neurons per animal, average for each individual animal used for statistical analysis)
Summary
Adversity in early postnatal life has a lasting negative impact on behavioural and emotional functioning of individuals.[1,2,3] Compelling evidence suggests that rodent maternal separation (MS), widely used to mimic early-life stress in human infants, leads to hyper-reactivity of the hypothalamic − pituitary − adrenal axis in adulthood.[4,5,6] This is accompanied by anxious or depressive-like behaviour or cognitive deficits in some instances.[7,8,9,10] In addition, these effects have been suggested to be downstream of neuroplasticity alterations. While the effects of adversity in early life possess a degree of permanence, peripubertal environmental enrichment (EE) has been shown to reverse its effects on anxiety,[25,26] depression[27,28] and learning deficits.[27,28,29] While reversibility of developmental adversity has been demonstrated in young animals, it is presently undetermined if EE in adulthood is able to reverse the persistent effects of early-life stress long after the event This is an important question because, if effective, an adult intervention can provide the opportunity to loosen the health burden of the temporally distant adverse past. We experimentally test whether MS results in BLA plasticity during adulthood, and if adult EE rescues the effects of MS on anxiety-like behaviour and BLA plasticity
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