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Cholinergic contributions to PASA and functional compensation in rats

Yegla B, Francesconi JA, Forde JC, Parikh V (2015) Cholinergic contributions to PASA and functional compensation in rats. Neuroscience 2015 Abstracts 253.11/V29. Society for Neuroscience, Chicago IL.

Summary: Neuroimaging studies have indicated increased recruitment of prefrontal regions coupled to reduced activation of posterior regions in task-performing older adults. This shift of activity in cortical networks is described as posterior-anterior shift in aging (PASA). What cellular mechanisms contribute to PASA and how it provides functional compensation for age-related decline in cognitive capacities remains unknown? Cortically-projecting forebrain cholinergic neurons modulate cortical networks and facilitate attentional processes. Here we examined whether cortical cholinergic inputs contribute to PASA expression and maintenance of attentional capacities in aging. Young (3 months) and aged (24 months) Wistar rats were trained in a sustained attention task (SAT) that requires them to distinguish between signal and non-signal events. After attaining criterion performance (_70% correct responses for 3 consecutive sessions), rats received bilateral infusions of cholinoselective immunotoxin 192-IgG SAP either into the prefrontal cortex (PFC) or posterior parietal cortex (PPC) to produce partial cholinergic deafferentation. Control animals were infused with saline. Following behavioral testing 4 weeks post-surgery, animals were perfused 45-min after the last session to examine changes in neuronal activity in the PFC and PPC using c-fos immunohistochemistry. Partial prefrontal cholinergic deafferentation in aged rats produced robust deficits in response accuracy on signal trials as compared to aged sham (p=0.04) and young lesion (p=0.03) rats. In general, c-fos expressing neurons were higher in the PFC of aged rats as compared to young rats. Although prefrontal neuronal activity did not differ between the aged sham and PFC lesion group, there was a trend for a higher neuronal activity in the PPC of the latter. Surprisingly, attentional performance displayed a negative correlation with the prefrontal activity. Neuronal activity in the PPC did not correlate with performance. PPC-infused aged rats displayed no lesion effect on SAT and performed better than aged rats infused with 192 IgG-SAP into the PFC (p=0.04). Moreover, partial loss of cholinergic inputs into the PPC reduced PFC recruitment as compared to PFC lesioned aged rats. Collectively, these data suggest that reduced cortical activity in young rats compared to aged rats may represent better neural capacity, or the efficient utilization of normal brain regions, for task performance. Moreover, PASA is not triggered by prefrontal cholinergic inputs, but these inputs may regulate the reciprocal interactions between the PFC and PPC networks to maintain optimal performance in aging.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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