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

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      1 , 1 , 1 , *
      Translational Psychiatry
      Nature Publishing Group

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          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.

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          Most cited references50

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          Neural consequences of environmental enrichment.

          Neuronal plasticity is a central theme of modern neurobiology, from cellular and molecular mechanisms of synapse formation in Drosophila to behavioural recovery from strokes in elderly humans. Although the methods used to measure plastic responses differ, the stimuli required to elicit plasticity are thought to be activity-dependent. In this article, we focus on the neuronal changes that occur in response to complex stimulation by an enriched environment. We emphasize the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning.
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            Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex.

            The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic-pituitary-adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons' capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.
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              Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons.

              The hippocampus and the amygdala are essential components of the neural circuitry mediating stress responses. The hippocampus, which provides negative feedback regulation of the stress response, is particularly vulnerable to degenerative changes caused by chronic stress. Unlike the hippocampus, relatively little is known about how stress affects the amygdala and the nature of its role in the stress response. Hence, we examined the effects of two different models of chronic stress on hippocampal and amygdaloid neuronal morphology in rats. In agreement with previous reports, chronic immobilization stress (CIS) induced dendritic atrophy and debranching in CA3 pyramidal neurons of the hippocampus. In striking contrast, pyramidal and stellate neurons in the basolateral complex of the amygdala exhibited enhanced dendritic arborization in response to the same CIS. Chronic unpredictable stress (CUS), however, had little effect on CA3 pyramidal neurons and induced atrophy only in BLA bipolar neurons. These results indicate that chronic stress can cause contrasting patterns of dendritic remodeling in neurons of the amygdala and hippocampus. Moreover, CIS, but not CUS, reduced open-arm activity in the elevated plus-maze. These findings raise the possibility that certain forms of chronic stress, by affecting specific neuronal elements in the amygdala, may lead to behavioral manifestations of enhanced emotionality. Thus, stress-induced structural plasticity in amygdala neurons may provide a candidate cellular substrate for affective disorders triggered by chronic stress.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                February 2016
                02 February 2016
                1 February 2016
                : 6
                : 2
                : e729
                Affiliations
                [1 ]School of Biological Sciences, Nanyang Technological University, Singapore , Singapore
                Author notes
                [* ]School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, Singapore 637551, Singapore. E-mail: rmitra@ 123456ntu.edu.sg
                Article
                tp2015217
                10.1038/tp.2015.217
                4872421
                26836417
                ec9ce281-bb95-4ce8-a087-754a0327ec5c
                Copyright © 2016 Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 01 June 2015
                : 18 October 2015
                : 02 December 2015
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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