Effects of ibotenic acid lesions of the mediodorsal thalamus on memory: relationship with emotional processes in mice

The effects of ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) on memory and fear reactivity in mice were studied. In the first experiment, MD subjects were submitted to a behavioral design allowing to study the relationship between memory and anxiety [Krazem A, Borde N, Beracochea D. Effects of diazepam and beta-CCM on working memory in mice: relationship with emotional reactivity. Pharmacol Biochem Behav 2001;68:235-44; Beracochea D, Krazem A, Jaffard R. Methyl beta carboline-3-carboxylate reverses the working memory deficits induced either by chronic alcohol consumption or mammillary body lesions in mice. Psychobiology 1995;23:52-8]. In a second experiment, MD-lesioned subjects were submitted to a GO/NOGO temporal alternation task involving two intertrial intervals (ITIs: 0 and 30 s). Lesioned subjects exhibited large bilateral mediodorsal thalamic lesions with small damage into the centromedial thalamic nucleus. In the first experiment, MD-lesioned animals performed normally a sequential alternation task involving fixed ITIs over seven successive trials (5 or 30 s); in contrast, MD-lesioned subjects exhibited deficits in the sequential task involving the same but mixed ITIs (30-5 s versus 5-30 s) the deficit being observed for the last trials of the series, regardless the ITIs used. MD lesions increased fear reactivity in an elevated-plus maze, and scores of anxiety were negatively correlated with performance in the mixed alternation schedule. The second experiment involving non spatial information extended results of the first experiment in showing that the deficit of MD-lesioned animals was not dependent on the ITIs separating trials. Overall, our data show that MD-lesioned subjects exhibit a cognitive impairment characterized by a difficulty to maintain an alternation rule in situations involving procedural variance, and this deficit could stem primarily from an increase of fear reactivity.