Bernard Cardo

Influence of ventral mesencephalic lesions on various spontaneous and conditioned behaviors in the rat

Abstract In the first set of experiments, we used groups of rats with either bilateral or unilateral ventral mesencephalic lesions and a group of controls in the following tests: diurnal exploratory activity, nocturnal activity, Skinner box and avoidance conditioning. Both groups of lesioned rats were found to be hyperactive in both types of activity tests, but those with unilateral lesions showed hyperactivity to a lesser extent. Neither of the experimental groups showed any evidence of extinction in the Skinner box. Rats with bilateral lesions learn a conditioned avoidance response more easily than the control animals but they also tend to show inadaptive behavior during the course of the testing procedure. In a second experiment, stimulating and recording electrodes were implanted in the lateral hypothalamus in certain of the animals of the three previous groups, having lesions as well. Such lesions were found to significantly decrease the threshold of arousal to central hypothalamic stimulation. From the results of our lesioning and testing procedures, a syndrome has been defined. However, the complex structure of the region that was destroyed does not permit a clear interpretation of the results.

Silver impregnation of dopaminergic systems after radiofrequency and 6-OHDA lesions of the rat ventral tegmentum

Nauta and Fink-Heimer silver impregnation techniques were used to study the anterior degeneration produced by radiofrequency (RF) or 6-OHDA lesions in the medial and lateral ventral mesencephalic tegmentum (VMT), substantia nigra and dorsalis tegmental decussation (DTD) in rats. Both Nauta and Fine-Heimer impregnating methods showed that RF lesion of the VNT produced degeneration in three major pathways: a ventral pathway corresponding to the fasciculus medialis prosencephali (FMP), an intermediate pathway projecting to the ventral thalamus, and a dorsal pathway to the medio-dorsal thalamus and to the nucleus lateralis habenulae. In addition, the Fink-Heimer method demonstrated prejections of the dopaminergic A10 and A9 cell group in the VMT to the nucleus caudatus after RF or 6-OHDA lesions. Projections to nucleus accumbens, tuberculum olfactorium, stria terminalis, and cortex frontalis were observed only after 6-OHDA lesion of the A10 cell group. Degeneration in cortex cinguli and entorhinalis was seen mainly after 6-OHDA lesion of the A9 cell group. The limbic forebrain cortical projections of the A10 group provide a coherent anatomical basis for the behavioral syndrome provoked by RF and 6-OHDA lesions in the VMT.

Self-stimulation in the dorsal pontine tegmentum in the rat

Self-stimulation behavior was examined in the pontine structures corresponding to the location of degenerative debris found after coagulation lesions of the ventral mesencephalic tegmentum. Part of these structures receive input from the fasciculus medialis prosencephali (FMP) fibers. Self-stimulation was not found after electrode placements in the nucleus pontis raphes or the nucleus olivaris superior. However, such behavior could be observed from placements in the substantia grisea pontis and the posterior part of the nucleus dorsalis raphes. Self-stimulation was observed from placements in all the regions of FMP projections except the Guddens nucleus dorsalis tegmenti.

Effects of posttrial hippocampal stimulation on acquisition of operant behavior in the mouse

One-hundred male mice were used of which 70 were bilaterally implanted in dorsal hippocampus. Three experiments were performed: (1) The threshold of electrical seizure was measured by bilateral stimulation of hippocampus. (2) The animals were introduced in a Skinner box and allowed to press 8 times on a lever. Each press was reinforced by a food pellet. Thirty seconds after the eighth press, the two hippocampi were stimulated for 80 sec. The intensity of current was half of the threshold determined in the first experiment. Mice receiving hippocampal stimulation showed better retention of learning than not implanted and nonstimulated mice. (3) In the third experiment the temporal gradient of hippocampal stimulation was estimated; after a 600-sec delayed stimulation no improvement of performances was observed.

Time-dependent improvement of performance on appetitive tasks in mice

Three experiments were carried out to study improvement of performance with time on appetitive tasks in BALB/c mice. Experiments 1 and 2 showed that a 24-hr interval between learning sessions significantly improves performance. It seems that there was a curvilinear relationship between this improvement and the 1st learning session duration. Experiment 3 showed that improvement is time-dependent and occured between 1 and 12 hr after the end of the learning session. These results confirm the hypothesis according to which the consolidation phase should be more an elaborative process than a simple fixing.

Effects of hippocampal electrical stimulation on long-term memory and on cholinergic mechanisms in three inbred strains of mice.

Two sets of experiments have been carried out in an attempt to determine the role of hippocampal cholinergic mechanisms in a long-term memory storage. Three inbred strains of mice were presented with two different learning tasks in order to estimate their long-term retention abilities as well as changes in this ability after a post-trial hippocampal stimulation. In parallel experiments the enzymes involved in acetylcholine metabolism were studied under different experimental conditions. Our results indicate: (a) The capacity for long-term memory of the BALB/c line is much greater than that of either the C57BL/6 or C57BR strain. (b) Hippocampal post-trial electrical stimulation leads to an improvement of this capacity in the BALB/c strain. This phenomenon is less pronounced in C57BL/6 and non-existent in C57BR mice. (c) Choline acetyltransferase activity in the hippocampus is significantly higher in BALB/c than in the other two strains. In BALB/c this enzyme activity is greatly changed by the post-trial stimulation whereas in the C57BL/L strain only a slight variation of enzyme activity is observed. No modification occurs in C57BR. The results suggest that the more active acetylcholine synthesizing enzyme in the hippocampus of BALB/c may be related to a greater acetylcholine availability, thus favoring the establishment of a long-term memory, perhaps by releasing greater amounts of acetylcholine in the hippocampus immmediately after the learning session. The electrical stimulation of the hippocampus acts to magnify or accelerate this phenomenon. It is suggested that the efficiency of the stimulation would be related to the genetically determined higher cholinergic activity of the hippocampus.

Neurochemical lesion of the locus coeruleus of the rat does not suppress the sedative effect of clonidine

The locus coeruleus of male rats was destroyed bilaterally by injection of 6-hydroxydopamine. Rats injected with the vehicle and normal rats served as controls. Starting 20 days after the lesion, the locomotor activity of all rats was measured for 5 min every day. For the first 6 days, the lesioned rats were significantly less active than control rats; from the 7th to the 15th day, on the other hand, the locomotor activity of the two groups of rats was the same. From the 16th day onwards, the sedative effect of small doses of clonidine (2.5-100 micrograms/kg) was measured in lesioned and control animals. In spite of an almost total loss of noradrenaline in the cerebral cortex and hippocampus and a 33% loss of noradrenaline in the brain-stem of the lesioned rats, the sedative effect of clonidine was the same as in the control rats. This result suggests that the sedation produced by clonidine is not dependent on presynaptically located alpha 2-adrenoceptors.

Effects of post-trial hippocampal stimulation on time-dependent improvement of performance in mice.

Abstract One hundred and fifty-two BALB/c male mice, of which 108 were bilaterally implanted in the dorsal hippocampus, were used to plot the performance level curve as a function of the inter-session delay on an incompletely learned continuous reinforcement appetitive conditioning in a Skinner ☐. All the animals were exposed to a 15-min first learning session and, 30 sec later, 76 animals were stimulated at half of the individual after-discharge threshold value for 80 sec. A 30-min second session took place after a time interval which varied from 200 sec to 24 h, and the performances of stimulated animals were compared to those of non-stimulated or non-implanted animals. In control animals, the performance observed during the first 5 min of the second session declined as the time between sessions increased up to an interval of 1 h, but then improved with further increase of this interval up to 6 h. On the contrary, in stimulated animals, the improvement of performances started at a 0.5 h interval and reached its maximum level at the end of the first hour. This level was always higher than in control animals. The results are interpreted as an indication that hippocampal stimulation acts upon the kinetics of reminiscence.

Intracranial self-stimulation from the dorsal raphe nucleus of the rat: effects of the injection of para-chlorophenylalanine and of alpha-methylparatyrosine.

A vigourous self-stimulation behavior was obtained from the ventromedian portion of dorsal raphe nucleus of the rat. The electrode placements differ from those of self-stimulation previously observed in this region. The injections of parachlorophenylalanine increase self-stimulation responding rate while the injection of alpha-methylparatyrosine produces a decrease. In the light of recent findings, the possibility of an activating intervention of CA system different from that of the dorsal noradrenergic bundle is discussed. Moreover, an inhibitory role of 5 HT neurons on self-stimulation behavior is evidenced.

Hypothalamic self-stimulation in three inbred strains of mice

Abstract Male mice from 3 inbred strains (DBA/2 Orl, BALB/c Orl and C57 BL/6 Orl) were implanted with a bipolar electrode in the hypothalamus and tested for self-stimulation. The 3 strains differed in performances: the BALB/c mice showed higher scores than the DBA/2 mice which themselves showed higher rates than the C57 BL/6 mice. These strains also differed in frequency, threshold and the nature of seizures suspending their self-stimulation behavior. Moreover, for each strain, a comparison between dorsal and ventral hypothalamus implantation was made. In the 3 strains dorsal implantation gave higher self-stimulation scores than ventral. On the other hand the seizures occured more frequently with ventral implantations.