Enrichment facilitates recovery of spatial memory but not retrosplenial immediate early gene hypoactivation after anterior thalamic lesions

Abstract

The anterior thalamus exists within an ‘extended hippocampal memory system’ and has extensive reciprocal connectivity with regions known to support spatial memory function such as the retrosplenial cortex (RSC). Damage to the anterior thalamic nuclei (ATN) in humans as a result of injury or neurodegenerative disease is associated with severe anterograde amnesia that is not therapeutically manageable. Rat models of ATN lesions have provided potential avenues of treatment through environmental enrichment, to ameliorate some of the lesion-induced deficits. Previously, behavioural recovery after enrichment did not accompany recovery of the striking immediate early gene (IEG) hypoactivation in the RSC found after ATN lesions, but the tasks used may not have been sensitive to RSC function. A modified radial arm maze (RAM) task sensitive to RSC lesions was therefore used to determine whether behavioural recovery was associated with improved expression of zif268, an IEG associated with spatial memory. Initially, water maze spatial tasks were used to establish spatial memory deficits prior to enrichment and to assess memory during the period of continuous enrichment and when overnight enrichment was continued thereafter. There was little or no evidence of recovery from substantial impairments in water maze memory tasks in rats with ATN lesions. However, subsequent testing on the RAM revealed clear, albeit partial, recovery of spatial memory in the enriched rats with ATN lesions. Nonetheless, levels of zif268 expression in the superficial layers of the granular RSC remained at the same level of hypoactivity of standard-housed ATN rats; instead, there was some evidence of recovered CA1 zif268 expression. ATN lesions were also associated with reduced cell counts in the mammillary bodies, which were also not recovered in enriched rats. These findings suggest that IEG expression in the RSC may not always be a critical biomarker for spatial memory function in rats.