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.

Relações entre machos de roedores muitas vezes se dão com a manifestação de comportamentos agressivos, em um embate em que se define um perdedor e um ganhador. O macho perdedor, de acordo com experimentos realizados no laboratório, apresenta comportamentos de defesa (avaliação de risco) quando exposto ao contexto da derrota social. Na expressão da defesa condicionada, estruturas do hipotálamo lateral devem ser importantes, que são também mobilizadas durante o confronto. No hipotálamo lateral destacamos a a parte justadorsomedial do hipotálamo lateral (LHAjd) que tem conexões com o sistema septo-hipocampal e projeta-se liga ao prémamilar dorsal (PMD), crítico para a expressão de comportamentos de defesa. Por outro lado, o PMD, que é uma estrutura altamente mobilizada durante o confronto social, tem conexões com o núcleo anteromedial do tálamo (AMv), estrutura já conhecida pela sua importância na aquisição da memória contextual e espacial. Assim, no presente trabalho, investigamos o papel do LHAjd na expressão e do AMv na aquisição da defesa condicionada na derrota social. Nos animais com lesão do LHAjd, observamos diminuição nos comportamentos de avaliação de risco durante exposição ao contexto. Nos animais com lesão do AMv o mesmo efeito. Dado os efeitos das lesões no AMv, elaboramos um paradigma para estudo em camundongos, a fim de se realizar inativações pontuais com farmacogenética nos neurônios glutamatérgicos em animais transgênicos durante a derrota social. Foi observado o mesmo padrão em camundongos transgênicos vGlut2-cre inativados com farmacogenética, não havendo influência nos comportamentos durante a derrota social. Inativações antes do contexto não causaram efeito na defesa condicionada. As inativações durante a derrota, no entanto, não tiveram efeito quando o residente agressivo está na exposição ao contexto. Os dados sugerem que o LHAjd tem papel na expressão da defesa condicionada, enquanto que o AMv tem papel na aquisição da defesa condicionada ao contexto, mas não no reconhecimento do residente agressivo. / Male rodents may interact aggressively, and from the agonistic encounter, it results a winner and a defeated animal. Accordingingly, the defeated male shows defensive behaviors (risk assessment) to the social defeat-related context. Contextual responses are known to rely on hippocampal processing, and one of the main targets of the hippocampal system is the justodorsomedial part of lateral hypothalamus (LHAjd), which projects to dorsal premamillary nucleus (PMD), known to be involved in the expression of social defensive behaviors. Notably, PMD, a hypothalamic site highly responsive to the social defeat, in turn, projects to the ventral part of thalamic anteromedial nucleus (AMv), previously shown to be involved in the acquistion of spatial and contextual memory to predatory threats. Thus, in present study, we investigated the role of LHAjd in expression and of AMv in acquisition of social defeat conditioned defensive behaviors. In LHAjd lesioned animals, we observed a decrease in risk assessment behaviors during exposute to the social defeat associated context , but not during the social defeat itself, suggesting a role in the expression of contextual but not in the innate social defeat. In AMv lesioned animals, we observed that the animals lost contextual defensive response, suggesting a role in the acquisition and/or expression of contextual responses. Next, using pharmacogetic inhibition, we investigated in vGlut2-cre transgenic mice the role of the AMV in the acquisition and expression of contextual defensive behavior. We have found that AMV inactivation prior to the social defeaf, but not prior to the exposure to the social defeat related context, was able to decrease contextual responses in animals tested withot the presence of the male aggressor, but not in the situation where the male aggressor was present. Overall, our results suggest that the LHAjd has a role in the expression of conditioned defense, and that the AMV is involved in the acquisision of contextual fear responses, but not in social recognition of aggressive male.