Hippocampal Stimulation Research Articles

Post-trial hippocampal and lateral hypothalamic electrical stimulation: Facilitation on long-term memory of appetitive and avoidance learning tasks

Mice of the BALB/c strain were bilaterally implanted with bipolar platinum electrodes either in the CA1 field of the dorsal hippocampus (HPC) or in the dorsolateral hypothalamus (HL) in order to compare the effects of postsession electrical stimulation on learning and memory. Two learning tasks were used, a discriminative food-reinforced conditioning task and a one-trial passive avoidance conditioning task. In the first two experiments, 30 sec after the end of the first learning session, subjects were stimulated during 80 sec. HPC stimulation intensity was half of afterdischarge threshold values; at HL stimulation intensity (10 μA per electrode) self-stimulation behavior (I.C.S.S.) was effective. Control groups constituted by nonoperated (n.i.) or operated nonstimulated animals (n.ST.HL and n.ST.HPC) were used. In the third experiment the HL stimulation intensities were lowered under the I.C.S.S. threshold values and their post-trial applications were tested on discriminative operant conditioning. Results from experiments I and II showed that HL as well as HPC stimulation improved performances registered during 24-hr delayed retention sessions. However, differences were observed between HL and HPC stimulation. First, HL appeared to be less effective than HPC stimulation on passive avoidance conditioning; second, compared to HPC-stimulated animals, HL-stimulated animals had over all the sessions significantly higher response rates during the food-reinforced sequences and during the nonreinforced sequences. In addition, the small lesions (200 μm in diameter) due to HL- and HPC-implanted electrodes disturbed in n.ST animals the pattern of retention, but this disruptive effect was task dependent and appears only in the discriminative operant conditioning. In the third experiment, subthreshold I.C.S.S. behavior intensities were found to have a significant facilitative effect. These data indicate (i) that post-trial HL as well as HPC stimulations have similar facilitative effects on retention of learning tasks whether controlled by positive or negative reinforcement; and (ii) that these effects are not dependent on a reward component. It was concluded that the facilitatory effects of these stimulations can be ascribed to their common ability to induce an arousal state during the post-training period.

Effects of hippocampal and amygdaloid stimulation on the firing of preoptic neurons in the proestrous female rat

Effects of hippocampal and amygdaloid stimulation on the firing of preoptic neurons in the proestrous female rat

Hippocampal inhibition and the fornix

Rats with chronically implanted electrodes in the dorsal hippocampus and fornix were operantly conditioned in a straight alley to press a bar placed at one end of the alley and to run for the water reward available at the other end. Both start and run times increased during hippocampal stimulation, but were differentially affected after electrolytic lesion of the fimbria-fornix system. The effect of stimulation on start times was abolished after the lesion, while the effect of stimulation on running remained unaltered. Perseverance of bar pressing was significantly higher during stimulation of the hippocampus, and this effect was abolished after fornix lesion. Threshold for stimulation effects increased with distance away from the pyramidal layer. These findings question the validity of a simple inhibitory explanation.

Electrode placement and kindling-induced experiemental epilepsy

Electrical stimulation of the amygdala, caudate, hippocampus, or entorhinal cortex two or three times per day led to the development and progressive intensification of elicited motor seizures in rats. After a few hundred stimulations ( X = 348 ) the subjects in all four experimental groups displayed spontaneous motor seizures which continued to recur even after the regimen of stimulation had been curtailed. Although the development of spontaneous interictal discharges at the stimulation site preceded the initial manifestation of spontaneous motor seizures in all rats kindled by amygdaloid or hippocampal stimulation and in a few of the animals kindled through entorhinal electrodes, such discharges were not recorded in the caudate subjects.

Ethanol dependence in the rat: Temporal changes in neuroexcitability following withdrawal

Electrodes were chronically implanted in the dorsal hippocampus of rats. Pretreatment levels of neural excitability were assessed by determining the duration of direct hippocampal electrical stimulation sufficient to induce forelimb clonus in each rat. Following baseline measurements the rats were administered an alcohol or sucrose-containing liquid diet and 19--22 days later were withdrawan. Two postwithdrawal stimulation sessions were conducted on each animal. Separate groups of ethanol-dependent and control rats were given primary stimulation sessions at 8 h, 24 h, 72 h, or 1 week postwithdrawal. Secondary stimulation sessions were conducted 1 week or 2 weeks postwithdrawal. The results from the primary stimulations indicated that ethanol-dependent animals exhibited significant neural hyperexcitability for at least 72 h, but not 1 week, postwithdrawal. Results from the secondary stimulations demonstrated the presence of a relative neural hypoexcitability in ethanol-dependent groups as compared to controls. The pattern of results suggests, however, that the observed relative neural hypoexcitability was not the direct result of ethanol withdrawal.

Reset of hippocampal rhythmical activities by afferent stimulation

Physostigmine induced theta rhythm and unit activity were recorded from the dorsal hippocampus in immobilized locally anesthetized rats. Correlations between theta and rhythmical unit activity and their modifications by hippocampal afferent stimulation were studied. The principal finding was that electrical stimulation of afferents reset theta and rhythmical unit activity in phase. Poststimulus theta displayed a variable frequency which depended upon the structure stimulated. Lower frequencies were evoked by septal, higher frequencies by entorhinal and reticular formation stimulations. When theta rhythms were absent either by spontaneous disappearance or as a consequence of lesions in the fornix superior or septum, the reset was not observed. The reset of the theta rhythms and unit activity by afferent stimulation, suggests that the hippocampus may participate in timing mechanisms.

Responses of thermosensitive preoptic and septal neurons to hippocampal and brain stem stimulation.

Responses of thermosensitive preoptic and septal neurons to hippocampal and brain stem stimulation.

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.

Inhibition of brain stem neuronal activity by electrochemical stimulation of the dorsal hippocampus in the freely moving proestrous rat

The involvement of the hippocampus with gonadotropin release and ovulation was studied in unanesthetized, freely moving rats. Monopolar stainless-steel or platinum electrodes were implanted bilaterally in the dorsal hippocampus; electrodes for recording multiunit activity were placed in the preoptic area and the mesencephalic reticular formation. After recovery from surgery and the completion of two or more consecutive 4-day estrous cycles, the animals were subjected to electrochemical stimulation of the dorsal hippocampus at 1200 h on the day of vaginal proestrus. Stimulation consisted of the passage of 50 μA anodal direct current through stainless-steel electrodes. Continuous multiunit recordings were obtained both before and as much as 5 or more hours after stimulation. Next day the uterine tubes were examined for ova as evidence of ovulation. Electrochemical stimulation of the dorsal hippocampus led to a decline in the activities of both the preoptic area and the mesencephalic reticular formation. Episodic focal spiking activity was observed in these animals, with a latency of 60 to 80 min after stimulation. Control rats, “stimulated” through platinum electrodes, did not show any consistent changes in their hypothalamic or midbrain electrical activity, nor did they reveal any sign of focal spiking activity. Hippocampal stimulation through stainless-steel electrodes led to the inhibition of spontaneous ovulation in 44% of the rats, whereas all animals bearing platinum electrodes ovulated in spite of the direct current. It is clear that the hippocampus is capable of influencing both neuronal and endocrine events, and our results suggest that the decrease in multiunit activity of the preoptic area and the mesencephalic reticular formation may be related to inhibition of the ovulatory surge of pituitary gonadotropins.

Effects of midbrain reticular formation, hippocampal, and lateral hypothalamic stimulation upon recovery from neophobia and taste aversion learning

In a neophobia paradigm midbrain reticular formation (MRF) electrical stimulation applied after consumption of a novel flavor produced a time-dependent disruption in recovery from neophobia (learned safety), while hippocampal and lateral hypothalamic stimulation had no disruptive effects. In a learned aversion paradigm neither MRF nor hippocampal or lateral hypothalamic stimulation applied after the illness experience produced a disruptive effect. In conjunction with previously reported effects of amygdala stimulation [12] the data support the existence of separate information processing systems mediating learned aversion and learned safety.

Electrophysiological investigation of cortico-hypothalamic relations in cats.

Projections of different parts of the orbito-frontal cortex, the basal temporal cortex, and the hippocampus on hypothalamic nuclei were studied by recording focal responses in acute experiments on cats anesthetized with pentobarbital and chloralose. The proreal gyrus was shown to have local projections in the latero-dorsal zones of the preoptic region, in the postral parts of the medial forebrain bundle, and also in the region of the lateral and posterior hypothalamus with the mammillary bodies. The orbital gyrus projects mainly to the latero-dorsal portions of the forebrain bundle, the latero-ventral part of the preoptic region, and the region of the lateral and latero-dorsal hypothalamic nuclei; projections from the orbital gyrus are relatively diffuse in character. The basal temporal cortex has diffuse projections in the central part of the preoptic region, in the latero-ventral parts of the medial forebrain bundle, and in the lateral mammillary body. No marked foci of activity were found in the hypothalamic structures during hippocampal stimulation. Diffuse projections of the hippocampus were traced in the ventral part of the preoptic region and the ventral regions of the medial forebrain bundle, and also in the lateral hypothalamus and in the lateral mammillary nucleus.

Dissociation of hippocampal EEG from its behavioral correlates by septal and hippocampal electrical stimulation

1. (1) Electrical stimulation of septum or hippocampus produced frequency-specific hippocampal synchrony and hippocampal desynchrony. 2. (2) Behaviors normally correlated with the occurence of hippocampal desynchrony continued during elicitation of synchony. Similarly, behaviors normally correlated with the occurence of synchrony continued during elicitation of desynchrony. Stated conversely, specific hippocampal patterns were elicited without eliciting the behaviors which occur when similar patterns are generated by the spontaneously behaving animal. 3. (3) These results suggest that the import of hippocampal patterns highly correlated with specific types of behaviors might best be sought in processes remote from the endpoint of motor performance per se.

Effect of food and water deprivation on hippocampal self-stimulation and poststimulation feeding

Barpressing for electrical stimulation of the dorsolateral hippocampus was facilitated by both food and water deprivation. These results were not simply attributable to a nonspecific effect of deprivation on self-stimulation; food deprivation but not water deprivation produced an increase in barpressing for lateral hypothalamic stimulation. Feeding elicited by dorsolateral hippocampal stimulation increased after food deprivation, but was not affected by water deprivation. These findings suggest a dissociation between the reinforcing consequences of hippocampal stimulation and the effects of hippocampal stimulation on feeding. In addition, there seems to be at least some degree of independence between the neural mechanisms underlying hippocampal reward and those underlying hypothalamic reward.

Effects of hippocampal and lateral hypothalamic electrical stimulation on hippocampal cholinergic mechanisms in BALB/c inbred mice

Electrical stimulation of the hippocampus (HPC) and of the lateral hypothalamus (LH) were found to have the same 24 h delayed effect on choline acetyltransferase activity. Since previous experiments demonstrated that these treatments had the same effect on memory storage processes, the present finding and earlier neurochemical investigations suggest that HPC and LH stimulation might act through a common hippocampal cholinergic mechanism.

Disruption of rabbit ( Oryctolagus cuniculus) nictitating membrane conditioning by posttrial electrical stimulation of hippocampus

Two experiments were conducted involving classical conditioning of the nictitating membrane response of rabbits with posttrial electrical brain stimulation. Hippocampal posttrial stimulation (PTS) presented immediately after each CS-US paired trial was found to cause massive disruption of conditioning by comparison with performance of either a cortical PTS group, an operated but unstimulated group, or an unoperated control group. The major effect of PTS was to postpone CR emergence. Once CRs began to occur, conditioning seemed to proceed normally regardless of the presence or absence of stimulation. Hippocampal PTS initiated after conditioning had no effect on the elicitation of conditioned responses. The results indicated that hippocampal PTS disrupted consolidation but did not affect either registration of stimuli or execution of unconditioned or conditioned responses. It was concluded that classical conditioning of the rabbit nictitating membrane response is an excellent model neural system for the investigation of neurophysiological aspects of memory.

Effets de la stimulation de l'hippocampe sur un apprentissage operant discriminatif chez la souris balb/c

Fifty-two male mice of the BALB/c strain were used in two experiments aimed at evaluating the effect of electrical posttrial stimulation of dorsal hippocampus on discrimination learning. After being trained to the bar-press in continuous reinforcement schedule (CRF), the animals were given 24 hr delayed sessions of operant discrimination. The hippocampal subseizure bilateral stimulation was applied during 80 sec, 30 sec after the end of the 1st discrimination session. The results showed that this treatment led to to an improvement of performances. This effect was a function of the time interval (1 or 5 days) between CRF training and operant discrimination learning. In addition the small hippocampal CA 1 field lesions produced by the electrode tips impaired performances in non-stimulated animals when pre- training and training were separated by a 5 days interval. The facilitation of discrimination performance produced by hippocampal stimulation was interpreted as due to facilitation of inhibitory processes involved in memory consolidation.

新しい中枢性筋弛緩薬Chlorphenesin Carbamateの脳波学的研究

Electroencephalographic (EEG) effects of chlorphenesin carbamate were investigated in rabbits with chronic electrode implants, and compared with those of chlormezanone and methocarbamol. Chlorphenesin carbamate (50 mg/kg i.v., 100 mg/kg i.d.) induced a drowsy pattern of spontaneous EEG consisting of high voltage slow waves in the cortex and amygdala, and desynchronization of hippocampal theta waves. Chlormezanone also elicited similar EEG changes but such were much more potent than chlorphenesin carbamate. Methocarbamol showed no effect on spontaneous EEG. Chlorphenesin carbamate caused sedation in this period and muscle relaxation was more potent than that of chlormezanone. The EEG arousal response to auditory stimulation and to electric stimulation of the posterior hypothalamus, centromedian thalamus and mesencephalic reticular formation was slightly depressed by chlorphenesin carbamate. Chlorphenesin carbamate, as with chlormezanone, markedly depressed the limbic afterdischarges elicited by hippocampal stimulation. These EEG effects of chlorphenesin carbamate were qualitatively similar to but much weaker than those of chlormezanone, whereas the muscle relaxant effect of chlorphenesin carbamate was more potent than that of chlormezanone.

Caudate and hippocampal inhibition of extralemniscal thalamic unitary responses and their blockade by strychnine in cats

Extracellular records were made of single extralemniscal thalamic unit activity evoked by electrical stimulation of the radial nerves in cats anaesthetized with chloralose. Effects of conditioning caudate and hippocampal stimulation on somatically evoked thalamic responses and the pharmacologi- cal characteristics of these effects have been studied. A total of 306 extralemniscal units were activated with somatotopic convergent properties at a mean response latency of 22.1 msec (range: 7–45 msec). Two hundred and forty five units, 80% of a total units recorded, were inhibited by conditioning caudate stimulation, and 229 units, 75% of a total number, were inhibited by conditioning hippocampal stimulation. There was no significant difference between the inhibitory influences from the caudate nucleus and the hippocampus. The onset latency for inhibition ranged from 10 to 30 msec for conditioning caudate and hippocampal stimuli and the duration of complete inhibition of the responses ranged from 130 to 400 msec and from 90 to 220 msec for stimulation of the caudate nucleus and the hippocampus respectively. These inhibitory influences exerted by the two brain structures were completely blocked by intravenous administration of strychnine (0.2–0.4 mg/kg) but not by intravenous doses of picrotoxin (2.0–4.0 mg/kg). From the physiological and pharmacological similarities between the caudate and hippocampal inhibitory influences on extralemniscal thalamic activity, possible involvement of the hippocampus as well as the caudate nucleus in perception of pain is discussed.

Analysis of neocortical electrical responses evoked by stimulation of various hypothalamic structures.

Evoked potentials (EPs) and extracellular unit activity were recorded in various parts of the neocortex of unanesthetized cats immobilized with succinylcholine. During hippocampal stimulation EPs of maximal amplitude are recorded in the anterior sigmoid gyrus with a latent period (LP) of 0.5-2.5 msec. The first component is a fast positive spike with a duration of about 1.5 msec. In the middle suprasylvian gyrus, hypothalamo-cortical (HC) EPs have a monophasic surface-negative configuration and are recorded after an LP of 2-6 msec. HC EPS in the anterior sigmoid gyrus can bind a rhythm of stimulation of up to 200 pulses/sec and are characterized not only by high functional mobility, but also by the property of posttetanic potentiation. The main positive wave appears to a testing stimulus with an interval of 7-10 msec. Complete recovery of all components of HC EP takes place at an interval of 50-150 msec. In response to the conditioning stimulus a biphasic change in excitability of the neurons is observed in the association areas of the anterior sigmoid and middle suprasylvian gyri of the neocortex. The maximal number of responding neurons in the deep layers of the cortex discharges in the period of development of the initial spike and the main positive wave of the HC EP.

Effect of hippocampal stimulation on evoked electrical activity of various brain structures

Functional relations between the entorhinal cortex and hippocampus were studied in acute and chronic experiments on cats. The dorsal hippocampus depresses electrical activity and responses of the ventral hippocampus evoked by stimulation of the entorhinal cortex and responses of the entorhinal cortex and ventral hippocampus to cutaneous electrical stimulation. The ventral hippocampus, on the other hand, facilitates evoked electrical activity of the dorsal hippocampus in response to stimulation of the entorhinal cortex, and also responses of the entorhinal cortex and dorsal hippocampus evoked by cutaneous electrical stimulation. The results suggest regional differences in nervous connections of the different parts of the hippocampus with the entorhinal cortex.