Functional Neuroanatomy and Neurophysiology

In order to study the role of non cognitive components, such as motivation, attention and emotionality, in the integration of learning and memory processes, and its neural substrates a neurogenetic approach has been followed in two genetic models, the Naples High Excitability (NHE) and Naples Low Excitability (NLE) rats using behavioral and functional imaging analysis. To this aim, adult male rats of the NHE, NLE and random-bred controls (NRB) were used in separate experiments. Behavioral analysis: rats were tested in an 8-arm radial maze (Olton-maze) with extra-maze cues. They were either kept at 80-85 % body weight (Exp. 1) or were fed ad-libitum and were given also two pieces of chocolate per day at about the testing time (Exp. 2). In both experiments, non reinforced maze exploration on day was followed by reinforcements of alley visits during shaping sessions and restriction of baited arms to a single arm. The latter was the same for each rat and differed among rats on consecutive days. The behavior was videotaped and analyzed off-line. The results indicate that (i) there was no difference among the three rat lines in working memory during non reinforced maze exploration, independent of the motivational level, (ii) at high motivational level (Exp. 1) rats of all three lines showed a higher working memory in finding the single baited arm than under low motivational level (Exp. 2), (iii) at low motivational level, both NHE/NLE showed a more stable reference memory than controls, and (iv) NHE rats paid little attention towards reinforcement upon visiting the baited arm. Functional imaging_analysis: brains were frozen, sectioned, and stained for quantitative histochemistry of cytochrome oxidase (C.O.) together with standards (brain homogenates) of known C.O. activity. Densitometric measurements converted to C.O. activity units (mmol/min/g wet weight tissue) were carried out across the anterior forebrain. Significant differences were found in medial frontal, entorhinal, and perirhinal cortex, and basolateral amygdala. NHE showed greater C.0. activity than NRB in entorhinal cortex (superficial layers) and lower activities in perirhinal cortex and basolateral amygdala. NLE showed greater C.O. activity than NRB in medial frontal cortex and lower activity in perirhinal cortex (dorsal region). Genetic selection led to greater metabolic capacity in the medial frontal cortex correlated to low behavioral reactivity and in the entorhinal cortex correlated to high behavioral reactivity. Lower metabolism in perirhinal cortex and basolateral amygdala was linked to high behavioral reactivity to spatial novelty. Thus, behavioral and functional neuroimaging analysis suggest that the neural substrates of cognitive and non cognitive components of exploration are underlied by different network operations in the neocortical and limbic cortices in the NHE and NLE rat lines. Supported by TELETHONItaly Grant E.513