In vivo intrahippocampal microinfusion of carbachol and bicuculline induces theta-like oscillations in the septally deafferented hippocampus.

In their laboratory the authors have previously demonstrated that hippocampal slices could be induced to generate trains of "theta-like" oscillations by whole-bath perfusions of carbachol. Until recently, it has not been possible to generate similar activity in the septally deafferented hippocampus of an otherwise intact brain by microinfusions of carbachol. This study presents a full report of the first demonstration of a theta-like oscillation in the in vivo, septally deafferented hippocampal formation. Rats were anesthetized with urethane and implanted with microinfusion cannulae in the region of the medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) and at single or multiple sites in the stratum moleculare of the fascia dentata. The MS/vDBB was microinfused with procaine hydrochloride to produce a reversible suppression lasting for approximately 20 minutes. Intrahippocampal microinfusions of carbachol or bicuculline alone (in the postprocaine condition of the MS/vDBB) failed to produce any theta-like oscillations. The combination of carbachol and bicuculline produced trains of theta-like oscillations during suppression of the MS/vDBB very similar to those seen in the slice preparations. The oscillations were blocked by intravenous administration of atropine sulfate, and they had the same depth profile as that of theta. Theta-on cells were shown to discharge in rhythmic bursts in synchrony with the oscillations. Thus, it would appear that the essential nature of the medial septal input to the hippocampal formation, for the generation of theta field activity in the intact brain, consists of a critical balance between cholinergic and GABAergic circuitry.

Facilitation of learning consecutive to electrical stimulation of the locus coeruleus: cognitive alteration or stress-reduction?

This chapter summarizes behavioral and neurochemical data on the delayed effect of locus coeruleus stimulation on learning capabilities in the rat. The initial observation showed that electrical stimulation of the locus coeruleus of a 15-day-old-rat improved the early stages of acquisition and extinction of a food-reinforced task performed 4 weeks later. Neurochemical lesion of the dorsal noradrenergic bundle performed 10 days before the stimulation did not attenuate the behavioral effect, whereas the lesion of the locus coeruleus proper suppressed the subsequent behavioral improvement. More recently we showed that the increase of adrenocorticotrophin release consecutive to a moderate stressful situation was significantly lower in previously stimulated rats than in implanted non-stimulated animals. Furthermore, we demonstrated that the neurochemical lesion of the locus coeruleus increased neophobia in the open-field as well as in a specific exploration task. Taken together these data strongly suggest that the long-term improvement in acquisition and extinction of locus coeruleus-stimulated rats results mainly from an attenuated stress reaction when these animals are confronted with a new environment (beginning of acquisition) or a new situation (beginning of extinction). Finally, we were interested in investigating the possibility of some long-term neurochemical modifications that could be related to the observed behavioral effects. The most significant modification observed concerned certain subpopulations of adrenoceptors in specific brain regions. By using specific ligands of the beta-, alpha 1- and alpha 2-adrenoceptors, we studied the long-term effect (4 weeks) of the locus coeruleus stimulation on the kinetic characteristics of these three sub-types of receptors in four brain areas (the cortex, hippocampus, hypothalamus and brainstem). No significant alteration in the density of beta binding sites was observed in any of the four structures analyzed; likewise locus coeruleus stimulation did not modify the density or affinity of the beta-, alpha 1- and alpha 2-receptors in the brainstem. The density of alpha 1- and alpha 2-receptors was significantly increased in the cortex whereas in the hippocampus only the density of the alpha 2-receptors was increased. Finally, a very large increase of the density of alpha 2-adrenoceptors was observed in the hypothalamus (113%). In each case the increase in receptor density was also associated with a decreased affinity. A behavioral counterpart of these changes in the kinetic properties of the alpha 2-receptors has been observed by using a pharmacological approach.(ABSTRACT TRUNCATED AT 400 WORDS)

Clonidine-induced sedation is not modified by single or combined neurochemical lesions of the locus coeruleus, the median and dorsal raphe nuclei.

Single or combined neurochemical lesions of the locus coeruleus, the dorsal and the median raphe nuclei were performed on different groups of rats. Starting 10 days after the lesion, the locomotor activity of all rats was measured for 5 min every day in an open-field. For the first 21 days all lesioned rats, independently of the lesion site, were significantly less active than controls, but from the 11th to the 16th day the locomotor activity of lesioned animals increased progressively and, thus on days 15 and 16, the mean activity of all lesioned groups was not significantly different from that of the controls. From the 17th day onwards the sedative effect of small doses of clonidine (5-100 micrograms/kg) was measured. Neither single nor combined lesions modified the response to clonidine and the linear decrease of activity produced by increasing doses of clonidine was the same in all groups, lesioned or not. Biochemical assays showed a marked loss of corresponding amines as a result of the lesions in cortex, hippocampus and the brainstem. These results suggest that the alpha 2-receptors involved in clonidine-induced sedation are located neither on noradrenergic fibers coming from the locus coeruleus, nor on serotoninergic fibers originating in the median and dorsal raphe nuclei.