Behavioral and cognitive changes after early postnatal lesions of the rat mediodorsal thalamus

Early insults to the thalamus result in functional and/or structural abnormalities in the cerebral cortex. However, differences in behavioral and cognitive changes after early insult are not well characterized. The present study assessed whether early postnatal damage to mediodorsal nucleus of the thalamus (MD), reciprocally interconnected with the prefrontal cortex, causes behavioral and cognitive alterations in young adult rats. Rat pups at postnatal day 4 received bilateral electrolytic lesion of MD, or a MD Sham lesion or were anesthetized controls; on recovery they were returned to their mothers until weaning. Seven weeks later, all rats were tested with the following behavioral and cognitive paradigms: T-maze test, open field test, actimetry, elevated plus maze test, social interactions test and passive avoidance test. Rats with bilateral MD damage presented with disrupted recognition memory, deficits in shifting response rules, significant hypoactivity, increased anxiety-like behavior, deficits in learning associations as well as decreased locomotor activity, and reduced social interactions compared to MD Sham lesion and anesthetized Control rats. The lesion also caused significant decreases in pyramidal cell density in three frontal cortex regions: medial infralimbic cortex, dorsolateral anterior cortex, and cingulate Cg1 cortex. The present findings suggest a functional role for MD in the postnatal maturation of affective behavior. Further some of the behavioral and cognitive alterations observed in these young adult rats after early MD lesion are reminiscent of those present in major psycho-affective disorders, such as schizophrenia in humans.