Distribution of urocortin 3 neurons innervating the ventral premammillary nucleus in the rat brain.

Urocortin 3 (Ucn 3) is a recently described peptide of the corticotropin-releasing factor family. Neurons expressing Ucn 3 mRNA and peptide are distributed in specific brain areas, including the median preoptic nucleus, the perifornical area (PFx), and the medial nucleus of the amygdala (MEA). Fibers immunoreactive to Ucn 3 are confined to certain brain nuclei, being particularly dense in the ventral premammillary nucleus (PMV). In studies involving electrolytic lesions and analysis of Fos distribution according to behavioral paradigms, the PMV has been potentially implicated in conspecific aggression and sexual behavior. However, the role that Ucn 3 plays in this pathway has not been explored. Therefore, we investigated the origins of the urocortinergic innervation of the PMV of Wistar rat in an attempt to map the brain circuitry and identify likely related functions. We injected the retrograde tracer cholera toxin b subunit into the PMV and found that 88% of the Ucn 3-immunoreactive fibers in the PMV originate in the dorsal MEA, and that few originate in the PFx. As a control, we injected the anterograde tracer biotin dextran amine into both regions. We observed that the PMV is densely innervated by the MEA, and scarcely innervated by the PFx. The MEA is a secondary relay of the vomeronasal system and projects amply to hypothalamic nuclei related to hormonal and behavioral adjustments, including the PMV. Although physiological studies should also be performed, we hypothesize that Ucn 3 participates in such pathways, conveying sensory information to the PMV, which in turn modulates behavioral and neuroendocrine responses.

Effect of intrahippocampal administration of anti-melanin-concentrating hormone on spatial food-seeking behavior in rats.

Melanin-concentrating hormone (MCH) is a hypothalamic peptide that plays a critical role in the regulation of food intake and energy metabolism. In this study, we investigated the potential role of dense hippocampal MCH innervation in the spatially oriented food-seeking component of feeding behavior. Rats were trained for eight sessions to seek food buried in an arena using the working memory version of the food-seeking behavior (FSB) task. The testing day involved a bilateral anti-MCH injection into the hippocampal formation followed by two trials. The anti-MCH injection did not interfere with the performance during the first trial on the testing day, which was similar to the training trials. However, during the second testing trial, when no food was presented in the arena, the control subjects exhibited a dramatic increase in the latency to initiate digging. Treatment with an anti-MCH antibody did not interfere with either the food-seeking behavior or the spatial orientation of the subjects, but the increase in the latency to start digging observed in the control subjects was prevented. These results are discussed in terms of a potential MCH-mediated hippocampal role in the integration of the sensory information necessary for decision-making in the pre-ingestive component of feeding behavior.

AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.

The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.

Comparative distribution of cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus of the capuchin monkey (Cebus apella) and the common marmoset (Callithrix jacchus).

Cocaine- and amphetamine-regulated transcript (CART) is widely distributed in the brain of many species. In the hypothalamus, CART neurotransmission has been implicated in diverse functions including energy balance, stress response, and temperature and endocrine regulation. Although some studies have been performed in primates, very little is known about the distribution of CART neurons in New World monkeys. New World monkeys are good models for systems neuroscience, as some species have evolved several behavioral and anatomical characteristics shared with humans, including diurnal and social habits, intense maternal care, complex manipulative abilities and well-developed frontal cortices. In the present study, we assessed the distribution of CART mRNA and peptide in the hypothalamus of the capuchin monkey (Cebus apella) and the common marmoset (Callithrix jacchus). We found that the distribution of hypothalamic CART neurons in these monkeys is similar to what has been described for rodents and humans, but some relevant differences were noticed. Only in capuchin monkeys CART neurons were observed in the suprachiasmatic and the intercalatus nuclei, whereas only in marmoset CART neurons were observed in the dorsal anterior nucleus. We also found that the only in marmoset displayed CART neurons in the periventricular preoptic nucleus and in an area seemingly comprising the premammillary nucleus. These hypothalamic sites are both well defined in rodents but poorly defined in humans. Our findings indicate that CART expression in hypothalamic neurons is conserved across species but the identified differences suggest that CART is also involved in the control of species-specific related functions.