Pierre Karli

Flight induced by infusion of bicuculline methiodide into periventricular structures

Microinjections of different doses of bicuculline methiodide (BM) were performed into the mesencephalic central gray (CG), the medial hypothalamus (MH) and lateral hypothalamus (LH). Flight reactions could be induced by microinjections of BM into either the CG or the MH. However, the type of flight behavior was different whether the injection was made in the CG or the MH. Furthermore, microinjections of 35 ng of BM in either structure produced an increase in locomotor activity whose time course differed according to the injected structure, and an increase in rearings was induced at MH but not at CG sites. At lateral hypothalamic sites, BM produced an increase in locomotor activity and rearings but no jump. These effects were antagonized in a dose-dependent manner by a local pretreatment with 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), a GABA agonist. These results suggest that (1) at the level of both the MH and the CG, a GABAergic link is involved in the inhibition of a substrate whose activation produces aversive effects, and (2) the aversive effect induced by CG BM microinjection seems to be different from that induced by MH BM microinjection.

Effects of mesencephalic central gray and raphe nuclei lesions on hypothalamically induced escape

Central gray (CG) lesions, in particular those located in its anterior part, provoked in about half of the lesioned rats a decrease in switch-off responses (SOR) induced by medial hypothalamic stimulation. Such a decrease in performance, followed by a partial or even total recovery, occurred only when the stimulation site was located in the postero-medial part of the medial hypothalamus. Occurrence and duration of the decrease in SOR did not depend on a possible severance of noradrenergic fibers that ascend from the locus coeruleus and course along the CG, since bilateral destruction of the locus coeruleus did not alter SOR. On the other hand, a lasting facilitation of SOR was observed in those rats in which the CG lesion extended more caudalle fully explained by an interruption of serotonergic fibers ascending from the raphé nuclei since lesions limited to the dorsal nucleus as well as combined lesions of the dorsal and medial raphé nuclei induced only a transient facilitation, whereas a lasting one was provoked both by raphé lesions that encroached upon the ventro-medial tegmentum and by CG lesions that only partially destroyed the dorsal raphé nucleus.

Effets aversifs et appe´titifs induits par stimulation me´sence´phalique et hypothalamique

Approach and escape latencies induced by hypothalamic or central grey stimulation were measured in the rat by means of a shuttle-box technique. In order to compare the effects obtained at various brain sites, the maximal value of the escape latency/approach latency ratio was determined within a given range of stimulation intensities. The ratio was shown to have high values at sites located in the ventral part of the central grey (in or near the dorsal raphe nucleus) or in the lateral hypothalamus. It was equal to zero for most of the sites located in the dorsal part of the central grey, as the rate regularly interrupted the stimulation without initiating it again. Intermediate values were obtained at sites located in the medial hypothalamus and in the dorsal pontine tegmentum.

Unilateral injection of GABA agonists in the superior colliculus: asymmetry to tactile stimulation.

A unilateral microinjection of each one of three different GABA agonists (Muscimol: 1.4 nmoles; Baclofen: 0.8 nmole; THIP: 10.7 nmoles) into the superior colliculus was found to result in a reversible asymmetry in the rats responsiveness to tactile stimulation. The rat was hyporeactive to stimulations applied contralaterally and hyperreactive to stimulations applied ipsilaterally to the infusion site. Furthermore, the rat showed ipsiversive turning in response to tactile stimulation applied either ipsi- or contralaterally to the infusion site. The results are discussed in relation with motor and sensory asymmetry produced by unilateral manipulations affecting the striato-nigro tectal system.

Morphine applied to the mesencephalic central gray suppresses brain stimulation induced escape

In the rat, microinjections of morphine (1.5 to 15 nmoles) into the dorsal part of the mesencephalic central gray (CG) were found to suppress both escape responding induced by electrical stimulations applied to either the medial hypothalamus (MH) or the CG and behavioral responsiveness to peripheral nociceptive stimulations. The time course of these two effects proved quite similar (Experiments 1 and 2). A systemic injection of naloxone reversed--in a dose dependent manner--the effects of morphine on the centrally induced escape responses (Experiment 3). The possibility that microinjections of morphine decrease both responsiveness to peripheral nociceptive stimulation and the reactivity of higher structures involved in the generation of aversive effects is discussed.

Escape and approach induced by brain stimulation:A parametric analysis

The study reported pursued two general aims: (a) to find out whether a brain-stimulation-induced escape response results from the bringing into play of similar mechanisms irrespective of whether the stimulation is applied to a site located in the mesencephalic central gray (CG), in the medial hypothalamus (MH) or in the lateral hypothalamus (LH); and (b) to verify whether escape and approach that can be induced by stimulating one and the same hypothalamic site result from a combined activation of two distinct neuronal systems, by means of specifying some of their functional characteristics that would possibly allow differentiation between them. Three experiments were carried out using a situation (shuttle-box) that allowed the measurement, for each given brain site, of both the time for which the rat underwent the stimulation before interrupting it (stimulation time, st., corresponding to an escape latency) and the time for which the animal remained non-stimulated before eventually restarting the stimulation himself (non-stimulation time, nst, corresponding to an approach latency). The following stimulation parameters were varied: the pulse duration (D), the stimulation intensity (I) and the interpulse interval (IPI = 1/stimulation frequency), i.e. the time interval that separated the beginning of a stimulating pulse from the beginning of the next one. The results obtained suggest the following. (1) Some of the mechanisms implicated in the elaboration of an escape response are similar irrespective of whether escape is induced by stimulating a site located in the CG, in the MH or in the LH.

Mapping of jumping, rearing, squealing and switch-off behaviors elicited by periaqueductal gray stimulation in the rat

Rats readily learn to escape from a stimulation applied to most mesencephalic periaqueductal gray (PAG) sites. In the present study, we tried to find out to what extent the differential effects induced by such stimulations actually reflect the existence of intraPAG functional subdivisions. To that end, a row of five electrodes was implanted into the PAG of each of 29 rats. Two kinds of effects were analyzed, the stimulation-elicited overt behaviors and the generalization of switch-off responding from one stimulation site to the others. Further, switch-off latency versus interpulse interval (IPI) relationships were established and both the threshold IPIs and the ceiling switch-off latencies were determined. The most commonly elicited behaviors (jumping, rearing and squealing) as well as the threshold IPIs and the ceiling switch-off latencies were mapped within the PAG. Switch-off behavior was elicited from all the stimulation sites studied. However, in the dorsal PAG the switch-off latency was found to decrease more steeply with decreasing IPI than it did in the ventral PAG. Switch-off generalization was less frequently observed between dorsally located stimulation sites. Jumps were most often elicited from dorsally and rostrally located PAG sites while squeals were more frequently elicited from the caudal part of the PAG and rearings from PAG subareas surrounding the aqueduct.

Escape induced by combined stimulation in medial hypothalamus and central gray

Abstract To elucidate some aspects of the functional interrelations between two brain structures whose activation induces aversive effects, electrical stimulations of varying intensity were applied to two sites, either located both in the medial hypothalamus (MH) or both in the mesencephalic central gray (CG), or one in each of the two brain regions. With the exception of a few pairs of sites located in the CG, the escape speed induced by a combined stimulation came close to the sum of the escape speeds respectively produced by an isolated stimulation applied to each site. At high intensities, however, the combined stimulation often induced an escape speed that lay below the sum of the escape speeds induced by the two isolated stimulations, which corresponds to a reduced effectiveness of the stimulations when applied in combination. Conversely, a combined stimulation at low intensities often induced an escape speed that clearly exceeded the sum of the escape speeds respectively induced by each stimulation applied alone. Such a mutual facilitation of the stimulation effects occurred regardless of the mutual location (ipsilateral or contralateral) of the MH and CG stimulation sites. Variations in the time interval (0.1–10 msec) between the pulses respectively stimulating each site did not provoke changes in the stimulation-induced escape speeds. The discussion bears on a possible convergence of different aversive inputs on a hypothetical common neural substrate as well as on the spatial and temporal interactions that may occur within such a substrate.

Effets de la stimulation de l'hypothalamus latéral, de l'amygdale et de l'hippocampe sur le comportement d'agression interspécifique rat-souris

Abstract Electrical stimulation of various sites located in the posterior two-thirds of the lateral hypothalamus elicited a clear facilitation of the mouse-killing response in spontaneous “killer”-rats; but interspecific aggressive behavior could be elicited in spontaneous “non-killers” only by stimulation of a very circumscribed zone located in the anterior hypothalamus between optic tract and fornix. A non-epileptogenic stimulation of amygdala or dorsal hippocampus did never interfere with release and course of the rats interspecific aggressive behavior. Any epileptogenic stimulation of one of these two nervous structures provoked inhibition of the mouse-killing response. The inhibitory effect of a hippocampal seizure discharge seems to be due to its propagation to other nervous structures, in particular to amygdala and hypothalamus. As to the effect of amygdaloid stimulation, it could not be made clear to what extent inhibition of the killing-response was due to development of neuronal synchronisation within the amygdala itself or to its propagation to the hypothalamus.

Distribution of GABA in the periaqueductal gray matter. Effects of medial hypothalamic lesions

Gas chromatography and chemical ionization mass spectrometry were used in order to measure the GABA (gamma-aminobutyric acid) concentration in a series of successive horizontal slices of the mesencephalic periaqueductal gray (CG) as well as in a series of successive frontal CG slices in the rat. Along the dorso-ventral axis, the GABA concentration (3.5-7 microgram/mg protein) was found first to increase and then to decrease, a maximum concentration being found at the level of the aqueduct. In contrast, no concentration gradient was found along the caudo-rostral axis. In an additional experiment, the medial hypothalamus (MH) was lesioned on one side and the effect of such a unilateral MH lesion on the caudo-rostral distribution of GABA was investigated. Fifteen days after performing the lesion, a graded decrease in GABA concentration--with a maximum in the rostral CG--was found to occur mainly on the lesioned side.