Recovery following anterior thalamic lesions.

Abstract

Extensive neural connections between the anterior thalamic nuclei (ATN) and the hippocampal system may explain the overlapping amnesic syndromes associated with diencephalic and medial temporal lobe brain injury. Despite the debilitating nature of the diencephalic amnesia, treatments for this condition are lacking. In rats, lesions to the ATN or hippocampus generally produce similar memory deficits, which further implicate these structures in a single functional memory system. First evidence is presented here that seemingly permanent and robust spatial working memory deficits seen after lesions to the ATN in rats are ameliorated by environmental intervention and pharmacological treatment. Post-operative housing of ATN-lesioned rats for 30 days in enriched environment resulted in marked improvements in performance on the spatial working memory task in the cross-maze irrespective of whether rats were exposed to enrichment immediately after surgery or enrichment was delayed by 40 days post-surgery. Long-term beneficial effects of enrichment were also demonstrated. Behavioural improvements were observed when Cerebrolysin - a neurotrophic compound - was injected intraperitoneally for 30 days post-surgery. The combination of enrichment and Cerebrolysin treatment was more effective in inducing recovery on a delayed memory test in the cross-maze task. The influence of enrichment and Cerebrolysin on the neural changes produced by ATN lesions was examined utilising an immediate early gene marker c-fos. Replicating previous studies, ATN lesions produced marked hypoactivity in the retrosplenial cortex, but this effect was not reversed by either enrichment or Cerebrolysin. Unexpectedly, enrichment produced further hypoactivation in this region. Although lesion-induced deficits in a radial-arm maze spatial discrimination task were not improved by enrichment, a related study in our laboratory showed that spatial reference memory can also be improved by enrichment in ATN rats. The current research provides strong support for potential opportunities for therapeutic intervention in the human domain.