Neural changes after training to perform cognitive tasks

Department of Neurobiology & Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Behavioural brain research (Impact Factor: 3.03). 12/2012; 241(1). DOI: 10.1016/j.bbr.2012.12.017
Source: PubMed


Cognitive operationsrequiring working memory rely on the activity of neurons in areas of the association cortex, most prominently the lateral prefrontal cortex. Human imaging and animal neurophysiological studies indicate that this activity is shaped by learning, though much is unknown about how much training alters neural activity and cortical organization. Results from non-human primates demonstrate that prior to any training in cognitive tasks, prefrontal neurons respond to stimuli, exhibit persistent activity after their offset, and differentiate between matching and non-matching stimuli presented in sequence. A number of important changes also occur after training in a working memory task. More neurons are recruited by the stimuli and exhibit higher firing rates, particularly during the delay period. Operant stimuli that need to be recognized in order to perform the task elicit higher overall rates of responses, while the variability of individual discharges and correlation of discharges between neurons decrease after training. New information is incorporated in the activity of a small population of neuronshighly specialized for the task and in a larger population of neurons that exhibit modest task related information, while information about other aspects of stimuli remains present in neuronal activity. Despite such changes, the relative selectivity of the dorsal and ventral aspect of the lateral prefrontal cortex is not radically altered with regard to spatial and non-spatial stimuli after training. Collectively, these results provide insights on the nature and limits of cortical plasticity mediating cognitive tasks.

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    ABSTRACT: Working memory is a cognitive function serving goal-oriented behavior. In the last decade, working memory training has been shown to improve performance and its efficacy for the treatment of several neuropsychiatric disorders has begun to be examined. Neuroimaging studies have contributed to elucidate the brain areas involved but little is known about the underlying cellular events. A growing body of evidence has provided a link between working memory and relatively long-lasting epigenetic changes. However, the effects elicited by working memory training at the epigenetic level remain unknown. In this study we establish an animal model of working memory training and explore the changes in histone H3 acetylation (H3K9,14Ac) and histone H3 dimethylation on lysine 27 (H3K27Me2) triggered by the procedure in the brain regions of the corticostriatothalamic circuit (prelimbic/infralimbic cortex (PrL/IL), dorsomedial striatum (DMSt) and dorsomedial thalamus (DMTh)). Mice trained on a spontaneous alternation task showed improved alternation scores when tested with a retention interval that disrupts the performance of untrained animals. We then determined the involvement of the brain areas of the corticostriatothalamic circuit in working memory training by measuring the marker of neuronal activation c-fos. We observed increased c-fos levels in PrL/IL and DMSt in trained mice 90min after training. These animals also presented lower immunoreactivity for H3K9, 14Ac in DMSt 24h but not 90min after the procedure. Increases in H3K27Me2, a repressive chromatin mark, were found in the DMSt and DMTh 24h after the task. Altogether, we present a mouse model to study the cellular underpinnings of working memory training and provide evidence indicating delayed chromatin remodeling towards repression triggered by the procedure. Copyright © 2015. Published by Elsevier Inc.
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