Role of the medial and lateral septum in a variable goal spatial problem solving task.

Rats with lesions to the medial (MS) or lateral septal (LS) nuclei were compared to normal controls (CNT) in the acquisition of a spatial working memory task. In this task, animals were first allowed to explore the unbaited three-table apparatus before being fed on one of the two possible goal tables. Animals were then tested on their ability to return to the table where they just had been fed. Only rats with medial septal damage were clearly impaired on this problem, an impairment that dissipated over days. In contrast, the performance of LS rats was not significantly different from controls. During the second phase of the experiment, the same animals received either atropine sulphate (50 mg/kg, IP), atropine methylnitrate (50 mg/kg, IP), or an equivalent volume of saline. Atropine sulphate produced a sharp decrease in performance by all subjects. Meanwhile, atropine methylnitrate produced a mild temporary deficit only in LS rats. Overall, these results confirm that the medial septum plays a crucial role in the acquisition of problem solving. In addition, these results also suggest that the lateral septum may play a possible role in some form of spatial behavior easily disrupted by atropine methylnitrate.

Meal-induced c-fos expression in brain stem is not dependent on cholecystokinin release.

Sprague-Dawley rats injected with a "physiological" dose of cholecystokinin octapeptide (CCK-8; 6 micrograms/kg ip) expressed c-fos immunoreactivity in the nucleus of the tractus solitarius (NTS) and the area postrema (AP) of the brain stem. Injection of the CCK-A antagonist L-364,718 30 min before CCK-8 injection eliminated c-fos expression in these regions. These findings support the hypothesis that CCK-8 induced c-fos expression is mediated by CCK-A receptors. We then tested whether a meal (Isocal) could activate c-fos, and, if so, whether this response could be eliminated by L-364,718. Ingestion of Isocal induced c-fos immunoreactivity in the NTS and AP. Meal-induced c-fos expression was not blocked by the CCK-A antagonist L-364,718. These findings demonstrate for the first time that a purely physiological nonnoxious stimulus, a meal, induces c-fos in the rat brain stem and indicate that feeding induces c-fos expression by a pathway that is largely, if not entirely, independent of CCK release.

Cholecystokinin-induced c-fos expression in the rat brain stem is influenced by vagal nerve integrity.

Exogenous cholecystokinin (CCK) activates brain stem neurons in the area postrema and nucleus of the tractus solitarius, primarily in regions where vagal afferent fibres terminate. The present experiments show that vagal sensory fibres mediate CCK-induced c-fos in brain stem neurons, based on the findings that perivagal capsaicin pre-treatment in seven out of eight cases reduced or ablated c-fos expression in these regions.

Oral-pharyngeal-esophageal and gastric cues contribute to meal-induced c-fos expression.

We recently demonstrated that a meal induces c-fos immunoreactivity in the dorsal motor nucleus of the vagus (DMV), the nucleus of the tractus solitarius (NTS), and the area postrema (AP) of the rat brain stem. This response was not eliminated by the cholecystokinin A (CCK-A) antagonist L-364,718, a finding suggesting that feeding induces c-fos immunoreactivity by a pathway that is largely independent of CCK-A receptor activation. Consequently, the role of alternative gastrointestinal cues in the induction of c-fos was investigated. The induction of c-fos after oral-pharyngeal and esophageal stimuli was examined by use of a sham-feeding procedure via a gastric fistula. Gastric fistula-closed and fed rats displayed c-fos immunoreactivity similar to that of meal-fed rats seen previously. Fistula-open and fed rats showed the same degree of staining in the more rostral section of NTS examined as fistula-closed and fed rats, but fewer c-fos-positive nuclei in the more caudal level of the NTS. The potential for gastric distension to induce c-fos was assessed after the inflation of a gastric balloon. Physiological inflation of the balloon produced marked c-fos induction primarily in the medial NTS.