Towards therapy to relieve memory impairment after anterior thalamic lesions: improved spatial working memory after immediate and delayed postoperative enrichment

Abstract

Injury to the anterior thalamic nuclei (ATN) is associated with severe amnesia in humans. To test the principle that these deficits may be amenable to intervention, the behavioural effects of postoperative housing in an enriched environment were examined in rats that received neurotoxic lesions of the ATN. As expected, rats with ATN lesions maintained in standard group-housing showed severe, and in this case long-term, deficits in a preoperatively trained non-matching-to-sample spatial working memory task. Thirty days of enriched housing, introduced either at 5 days (Experiment 1) or delayed until 40 days post-surgery (Experiment 2) markedly reduced this working memory impairment, including evidence of improved utilization of spatial cues. The treatment gains found in Experiment 2 were maintained at 4 months post-surgery despite no further enrichment. ATN lesions also retarded the postoperative acquisition of spatial discrimination problems in Experiment 1, irrespective of the separation between target arms, but this impairment was not ameliorated by the prior enrichment. This study provides the first evidence of substantial recovery of severe, and otherwise long-lasting, spatial working memory deficits after ATN brain injury and suggests that further investigation on the extent of possible recovery of function in animal models of diencephalic amnesia is warranted.