Septal Stimulation Research Articles

Piriform cortex efferents to the entorhinal cortex in vivo: kindling-induced potentiation and the enhancement of long-term potentiation by low-frequency piriform cortex or medial septal stimulation.

The entorhinal cortex receives input from many cortical areas and mediates the flow of information between these sites and the hippocampal formation. Long-term synaptic plasticity in cortical efferents to the entorhinal cortex may contribute to the transmission of neural activity to the hippocampus, as well as the storage of information, but little is known about plasticity in these pathways. We describe here the use of evoked field potential recordings from chronically implanted electrodes in the rat entorhinal cortex to investigate synaptic plasticity in the large piriform (olfactory) cortex projection to the superficial layers of the entorhinal cortex. Both kindling-induced potentiation and long-term potentiation (LTP) were tested. In addition, we attempted to modulate LTP induction by the co-induction of frequency potentiation and by the co-activation of the medial septum. Epileptogenic kindling stimulations of the piriform cortex (1-s, 60-Hz trains 3 times/day for 5 days) were found to result in a reliable potentiation of field responses evoked by piriform cortex test pulses. Non-epileptogenic tetanization of the piriform cortex with 400-Hz 16-pulse trains reliably resulted in LTP effects. These effects could be augmented by embedding brief LTP induction stimuli within 11-pulse, 15-Hz trains that alone produce only frequency potentiation. Co-activating the medial septum with 10-Hz trains, just prior to tetanization of the piriform cortex, augmented LTP of piriform cortex inputs to the entorhinal cortex in an input-specific manner. All potentiation effects were found to last for periods of weeks. These findings demonstrate that both epileptogenic and non-epileptogenic piriform cortex stimulation induces lasting potentiation of population field responses in the entorhinal cortex of the awake rat. The LTP effects were inducible in a graded manner and were sensitive to the temporal context of stimulation. The finding that low-frequency activation of the septum can enhance plasticity in the entorhinal cortex adds to a body of data indicating a role for the medial septum in contributing to theta activity and plasticity in both the entorhinal cortex and hippocampal formation.

Erratum to: Dependence of the proactive behavioral effects of theta-driving septal stimulation on stimulation frequency and behavioral experience: 2. Continuously and partially reinforced running

Two experiments were conducted with Sprague-Dawley rats, chronically implanted with medial septal stimulating and subicular recording electrodes, to test the hypothesis that low-frequency electrical stimulation of the septal area, driving the hippocampal theta rhythm, has frequency-dependent proactive efects on behavior: specifically, that theta-driving stimulation at 7.5 Hz gives rise to tolerance for subsequent frustrative nonreward, whereas stimulation at 7.7 Hz sensitizes the animal to this event. After a 10-day stimulation regime (fifteen 6-sec stimulation trains at a 30-sec intertrain interval daily; 7.5 Hz in Experiment 1, 7.7 Hz in Experiment 2), rats were trained to run in a straight alley for food reward at 1 trial/day for 16 days on either a continuous reinforcement (CRF) or a partial reinforcement (PRF) reinforcement schedule followed by extinction; implanted controls were not stimulated but were otherwise treated identically. As predicted by the hypothesis, the partial reinforcement extinction effect (PREE; i.e., greater resistance to extinction after PRF than after CRF training) was proactively reduced by 7.5-Hz stimulation, owing to lowered resistance to extinction in the stimulated PRF-trained animals relative to their nonstimulated controls; whereas, again as predicted, the PREE was increased by 7.7-Hz stimulation, owing both to increased resistance to extinction in the stimulated PRF condition and reduced resistance to extinction in the stimulated CRF condition relative to the respective non-stimulated control groups. Thus the proactive behavioral effects of 7.5- and 7.7-Hz stimulation were opposite in sign, dependent in both cases upon the schedule of reinforcement encountered subsequent to stimulation, and consistent, respectively, with stimulation-induced tolerance for nonreward (7.5 Hz) or sensitization of the response to nonreward (7.7 Hz).

Stimulation of the lateral septum attenuates immobilization-induced stress ulcers

Rats with electrodes implanted in their dorsolateral septal area underwent a cold-immobilization restraint procedure during which the experimental group received electrical stimulation while the control group did not. Electrical stimulation of the dorsolateral septal region clearly reduced the number of gastric ulcers formed during the cold-immobilization stress procedure. The pattern of results with septal stimulation contrasts with that seen by other investigators after stimulation of the central amygdaloid nucleus. The mitigation of stress-induced ulceration after lateral septal stimulation is consistent with the proposed function for the lateral septal area in relief from aversive emotional states.

Dependence of the proactive behavioral effects of theta-driving septal stimulation on stimulation frequency and behavioral experience: 2. Continuously and partially reinforced running

Two experiments were conducted with Sprague-Dawley rats, chronically implanted with medial septal stimulating and subicular recording electrodes, to test the hypothesis that low-frequency electrical stimulation of the septal area, driving the hippocampal theta rhythm, has frequency-dependent proactive efects on behavior: specifically, that theta-driving stimulation at 7.5 Hz gives rise to tolerance for subsequent frustrative nonreward, whereas stimulation at 7.7 Hz sensitizes the animal to this event. After a 10-day stimulation regime (fifteen 6-sec stimulation trains at a 30-sec intertrain interval daily; 7.5 Hz in Experiment 1, 7.7 Hz in Experiment 2), rats were trained to run in a straight alley for food reward at 1 trial/day for 16 days on either a continuous reinforcement (CRF) or a partial reinforcement (PRF) reinforcement schedule followed by extinction; implanted controls were not stimulated but were otherwise treated identically. As predicted by the hypothesis, the partial reinforcement extinction effect (PREE; i.e., greater resistance to extinction after PRF than after CRF training) was proactively reduced by 7.5-Hz stimulation, owing to lowered resistance to extinction in the stimulated PRF-trained animals relative to their nonstimulated controls; whereas, again as predicted, the PREE was increased by 7.7-Hz stimulation, owing both to increased resistance to extinction in the stimulated PRF condition and reduced resistance to extinction in the stimulated CRF condition relative to the respective non-stimulated control groups. Thus the proactive behavioral effects of 7.5- and 7.7-Hz stimulation were opposite in sign, dependent in both cases upon the schedule of reinforcement encountered subsequent to stimulation, and consistent, respectively, with stimulation-induced tolerance for nonreward (7.5 Hz) or sensitization of the response to nonreward (7.7 Hz).

Dependence of the proactive behavioral effects of theta-driving septal stimulation on stimulation frequency and behavioral experience: 1. Leverpress experiments

We tested whether hippocampal theta has frequency-specific functions related to anxiety. Male rats received chronic implants of septal and subicular electrodes to elicit and record theta. Two to six weeks later, experimental rats received thirty 3-sec trains of theta-driving septal stimulation daily for 10 days; controls were connected to the apparatus, but not stimulated. The results were as follows: 7.7-Hz or 8.3-Hz theta driving before acquisition of a fixed-ratio 5 (FR5) barpress response increased its resistance to extinction subsequently (Experiment 1). In contrast, 7.5-Hz theta driving before acquisition of the FR5 response facilitated its later extinction (Experiment 2). Finally, 8.3-Hz theta driving after acquisition of the FR5 response also facilitated its extinction (Experiment 3). Thus, theta-driving stimulation (1) has nonassociative behavioral effects, which (2) are exquisitely frequency specific (Experiments 1–2) and (3) are modified by associative processes during acquisition of an appetitive response (Experiment 3). Theta is involved in producing anxiety, but not via spatial, motor, or memorial mechanisms.

Further characterization of kindling antagonism.

Alternating stimulation of two sites in the forebrain culminates in typical kindling of generalized seizures from one site (dominant), whereas the other site (suppressed) supports only nongeneralized seizures for as long as stimulation of the dominant site continues, a phenomenon referred to as kindling antagonism. With the termination of stimulation of the dominant site, however, seizures provoked from the suppressed site eventually generalize, a progression thought to reflect the resumption of kindling from a previous point of arrest. To further assess the nature of kindling antagonism, we established antagonism between the amygdala and the septal area and subsequently evaluated the development of seizures provoked by stimulation of sites distal to the dominant site (always the amygdala). In Experiment 1, a 30-d stimulation-free period imposed after the establishment of antagonism failed to result in immediate generalization of seizures provoked from the suppressed site (septal area) in seven of eight rats. Although these results suggest that antagonism reflects an actual arrest of kindling rather than a transient inhibition of seizures, they are not entirely unambiguous: Rats exposed to the prolonged stimulation-free period required only half the number of septal stimulations for the expression of a generalized seizure as compared to rats receiving septal stimulation immediately after the establishment of antagonism. The latter finding is suggestive of a transient component of antagonism. In Experiment 2, development of generalized seizures from the previously naive right amygdala was virtually identical in rats previously kindled from the left amygdala and in rats expressing antagonism between the septal area and left amygdala. Development of generalized seizures from the right amygdala was faster than from the left amygdala in both groups of rats, however, suggesting that the expression of seizures provoked from the suppressed site after the establishment of antagonism does not involve a general impairment or enhancement of transfer. Experiment 3 revealed that radio-frequency lesions of the dominant site (amygdala) after the establishment of antagonism did not alter the subsequent development of generalized seizures from the suppressed site (septal area). This suggests that the expression of generalized seizures from the suppressed site after the establishment of kindling antagonism is not dictated by the functional state of the dominant site.

Regional patterns of brain 2-DG uptake produced in mice by electrical stimulation of the septum, hypothalamus, or entorhinal cortex: Relation to functional neural pathways involved in memory mechanisms

The regional pattern of brain 2-DG uptake was studied in different groups of mice that received electrical stimulation of the medial septum (MS), dorsomedial hypothalamus (DMH), or lateral entorhinal cortex (LEC). Site selection was based on the findings of previous experiments, in which there was an improvement in long-term retention performance following MS stimulation when applied during the first 60 sec of posttraining, following LEC stimulation (when applied 15–60 min posttraining), and following DMH stimulation (when applied any time within the first 60 min of posttraining). The global comparison of the patterns of stimulation-induced increases in 2-DG labeling showed that MS stimulation induced specific increases in 2-DG labeling predominantly in the hippocampal formation, whereas DMH stimulation produced increased labeling in the caudate putamen, the mediodorsal thalamus, and the entorhinal cortex. Globally, LEC stimulation produced a large cortical activation, and more particularly, it induced a specific activation of the parietal cortex. Perforant-path lesions suppressed the LEC-stimulation-induced labeling in the hippocampus but did not alter the increased labeling in the amygdala and in the cortical areas. As with previous data obtained from experiments combining training and 2-DG labeling, the functional neural networks involved in these differential labeling patterns are discussed in terms of their possible implication for early or late phases of memory processing.

Minimal changes with long-term administration of anxiolytics on septal driving of hippocampal rhythmical slow activity.

In free-moving male rats, the function relating frequency to the threshold current required to drive hippocampal rhythmical slow activity (RSA; "theta") with septal stimulation has a minimum at 7.7 Hz. Classical anxiolytics all increase thresholds in the region of 7.7 Hz, and so does the novel anxiolytic buspirone. However, unlike classical anxiolytics, 2 or 3 weeks are normally required for the onset of the clinical effects of buspirone. This study tested the effects of long-term administration of chlordiazepoxide and buspirone on septal driving of RSA. Separate groups of naive rats received three IP injections per day of chlordiazepoxide (0.4 mg/kg), buspirone (0.1 mg/kg) or saline for 50 days. Both chlordiazepoxide and buspirone increased thresholds at 7.7 Hz, as expected. These acute effects were not significantly changed with chronic administration. Buspirone and chlordiazepoxide produced similar, statistically significant, but small cumulative reductions in thresholds at 6.9 Hz. The present experiments suggest that if the effects of anxiolytic drugs on septally driven RSA provide any basis for their clinical action, then classical anxiolytics may have two actions: an immediate effect on euphoria and tension and a delayed effect on anxiety proper--with buspirone sharing only the latter effect.

A comparison of the acute effects of a tricyclic and a MAOI antidepressant on septal driving of hippocampal rhythmical slow activity

In free-moving male rats, the function relating frequency to the threshold current required to drive hippocampal rhythmical slow activity (RSA) with septal stimulation has a minimum at 130 ms. Both classical anxiolytics (e.g. benzodiazepines) and the novel anxiolytic buspirone show similar effects on septal driving of RSA. The tricyclic antidepressant imipramine may be as effective as anxiolytic drugs in treatment of generalized anxiety disorder. The antidepressant monoamine oxidase inhibitor phenelzine has also been reported to be effective in treating anxiety, but this may reflect an action on "atypical depression" rather than "anxiety". The present study therefore compared the effects of acute administration of imipramine and phenelzine on septal driving of RSA to determine whether either would mimic anxiolytics in this test. Rats were chronically implanted with septal stimulating electrodes and subicular recording electrodes. Three groups of rats received IP injection of either imipramine (5.9-13.3 mg/kg or 13.3-30 mg/kg) or phenelzine (0.2-5.4 mg/kg). The effects produced by imipramine were very similar to the effects produced by anxiolytic drugs. In contrast, the effects produced by phenelzine were essentially opposite to those of both anxiolytic drugs and imipramine. The present experiment suggests that imipramine may act as a true anxiolytic, in addition to its conventional antidepressant properties. In contrast, phenelzine may be effective in cases where the etiology is essentially that of depression even when the symptomatology appears to be that of anxiety.

Relationships between septo-hippocampal cholinergic activation and the improvement of long-term retention produced by medial septal electrical stimulation in two inbred strains of mice.

This experiment was designed to highlight the relationships between septo-hippocampal cholinergic activation and the processing of memory consolidation. For that purpose, we have analyzed the consequences of a medial septal electrical stimulation (100 Hz, 30 microA) applied soon after partial acquisition session of an appetitive operant conditioning task on in vivo hippocampal cholinergic activity on the one hand and on subsequent retention 24 h later on the other hand. For maximize our data base for such comparison we used two neurochemically and behaviorally distincts strains of mice, BALB/c and C57BL/6. In these conditions, our results showed that BALB/c mice evidenced better performance in retention than C57BL/6 mice after medial septal stimulation. On the other hand, the stimulation applied in resting conditions produced a moderate and similar hippocampal cholinergic activation in the two strains. Moreover, in BALB/c mice the only strain which exhibited good consolidation capacities the stimulation do not induced any additive effect on the substantial increase of the hippocampal cholinergic activity produced by the previous acquisition session. Finally, a correlative study realized in C57BL/6 mice seems to indicate that the higher the hippocampal cholinergic activity was the lower were the consolidation capacities. These results lead us to suggest that the improvement of memory consolidation induced by the medial septal stimulation is the consequence of the recruitment of non cholinergic elements located close to the electrode tip. Consequently the septo-hippocampal cholinergic activation is more likely to facilitate certain information processes prior to the consolidation mechanisms proper.

Effects of long-term administration of antidepressants on septal driving of hippocampal RSA.

All classical anxiolytics raise the thresholds of septal-elicited hippocampal RSA overall, but do so mostly at 7.7 Hz (130 ms). The novel anxiolytic/antidepressant buspirone shows partial similarity with classical anxiolytics on septal driving thresholds. These effects of both the classical and novel anxiolytics are unchanged by long-term administration. The present experiment tested whether the tricyclic antidepressant imipramine and the monoamine oxidase inhibitor antidepressant phenelzine share these common effects of classical and novel anxiolytics with long-term administration. Rats, implanted with septal stimulating electrodes and subicular recording electrodes, received 15 mg/kg imipramine (twice per day) and 2 mg/kg phenelzine (once per day) for 28 days. Chronic administration of imipramine mimicked the documented effects of anxiolytics while chronic administration of phenelzine produced essentially opposite effects to the effects of anxiolytics on septal driving of RSA. Since both acute and chronic administration of imipramine but not phenelzine also produce similar effects to anxiolytics on the frequency of reticular-elicited hippocampal RSA, we suggest that (1) imipramine has a separate anxiolytic action, in addition to its antidepressant action; and (2) phenelzine may have no central anxiolytic action despite its capacity to relieve somatic symptoms in atypical depression.

Medial septal area modulation of sustained negative shifts in awake rabbits.

Experiments were performed on rabbits with chronically implanted Ag-AgCl electrodes over occipital cortex and chrome-nickel stimulation electrodes in the medial septal area. Visual evoked potentials (VEP) were elicited by means of randomly occurring flashes. After measuring the N1-amplitude of the VEPs, responses with N1-1 amplitudes below a previously determined discriminative value were reinforced by a weak footshock 1.5 S1 after the flash. In the group of high-amplitude VEP we found longer negative shifts than in the group of low-amplitude VEP, starting 600-700 ms after flash and lasting up to the end of the observed time range. The stimulation of medial septal area (0.5 mA, 6 imp/s) during the normal flash application led to a delay of the maximum of this negative shift which returned now to baseline within the observed range. The amplitude of these sustained negative shifts was larger during septal stimulation. Larger negative shifts followed high-amplitude VEP than the low-amplitude ones. Repetition of usual flash application without septal stimulation after a 10 min break turned the negative shift to normal. After electrolytic destruction of medial septal area this late negative shift vanished without any restitution.

Long-term results of stimulation of the septal area for relief of neurogenic pain.

Chronic brain stimulation may be a useful method of treating chronic neurogenic pain. However, the knowledge about the basic mechanisms responsible for pain relief is still fragmentary, and the clinical results have often been inconsistent even contradictory. In an attempt to explore the possibility of stimulating other cerebral targets, stimulating electrodes have been implanted in the septal region in addition to stimulation in the sensory thalamus or the periventricular grey. In 19 patients subjected to septal stimulation, 12 experienced satisfactory relief of their spontaneous pain together with abolition of allodynia. There were no untoward side effects. The follow-up ranged from 1 to 10 years. Our result suggest that the septal area may be a suitable alternative target for chronic brain stimulation.

Quantitation of mapping uncertainty in Wolff-Parkinson-White syndrome

The purpose of this study was to quantitate the uncertainty inherent in the electrophysiologic mapping of ventricular preexcitation as seen in Wolff-Parkinson-White syndrome. An ink-coated needle electrode was constructed to serve as a point source of unipolar stimulation along the atrioventricular junction. Activation times for 11 ventricular mapping sites at the atrioventricular junction were measured for each stimulation point. Maps were successfully completed for 18 right free wall and 14 posterior septal stimulation points. The activation time at the mapping site closest to the stimulation point was termed the index activation time. Activation times identical to the index activation time were noted at 1.3 +/- 0.5 mapping sites for each free wall stimulation point and 1.9 +/- 0.9 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). Activation times falling within 5 msec of the index activation time were noted at 2.4 +/- 1.0 mapping sites for each free wall stimulation point and at 3.9 +/- 1.4 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). The uncertainty of electrophysiologic mapping can be quantitated, and this error should be considered when making inferences regarding the anatomy of accessory pathways based on electrophysiologic data. A knowledge of the uncertainty inherent in the localization of accessory atrioventricular connections by electrophysiologic mapping can be used to plan borders of surgical dissection that will account for this uncertainty at a 95% confidence level.

Post-training medial septal stimulation improves spatial information processing in BALB/c mice

The experiment reported here was designed to highlight the effects of medial septal nucleus electrical stimulation on memory processes. To that end, we have used a learning task carried out in a 4-hole board in which animals were successively presented with the location of 2 baited holes. Under these conditions, the consequence of a weak stimulation (30 microA peak to peak, 80 s in duration) applied 30 s after acquisition of these 2 separate spatial informations was assessed on a retention test 24 h later. The results indicated that performance of stimulated animals was improved by medial septal stimulation as shown by an increase in the time duration of exploration of the second previously baited hole. However, post-training stimulation also produced a significant avoidance of the first previously baited hole not observed in the control groups. These results suggest that medial septal stimulation improves retroactive inhibition involved in working memory processes, thus leading to better retention of this kind of learning situation.

Neurochemically dissimilar anxiolytic drugs have common effects on hippocampal rhythmic slow activity

Previous experiments have shown that anxiolytic drugs reduce the frequency of hippocampal rhythmic slow activity, induced by high frequency stimulation of the reticular formation and flatten the function relating threshold septal stimulation to the frequency of driven rhythmic slow activity. All of the drugs involved are known to augment GABAergic transmission. The present experiments investigated the effects of the novel anxiolytic compound buspirone which, unlike conventional anxiolytics, does not interact with GABA, yet is a clinically effective anxiolytic. Buspirone (0.156–40 mg/kg, i.p.) was found to reduce the frequency of reticular-elicited rhythmic slow activity, in a similar manner to chlordiazepoxide (0.019–20 mg/kg, i.p.). Buspirone did not change the linearity of the voltage-frequency function. Buspirone (10 mg/kg, i.p.) also altered the threshold for septal driving of rhythmic slow activity, in a similar manner to classical anxiolytics. The combination of chlordiazepoxide (5 mg/kg, i.p.) with corticosterone (0.2 mg, s.c.) removed the minor differences between buspirone and chlordiazepoxide in both the septal and reticular tests. These results show that buspirone altered the control of rhythmic slow activity in the hippocampus, in a manner which appeared functionally equivalent to other anxiolytics but which depends on mechanisms which are likely to be neurally and pharmacologically distinct from those of other anxiolytic drugs.

Further Evidence that the Septum is not part of the Main Pathway of the Milk Ejection Reflex in the Rat

Abstract The possible role of the medial septum in the control of oxytocin release and of the milk ejection reflex induced by suckling was investigated in lactating rats by using electrical stimulations and lesions. In anaesthetized animals, brief electrical stimulation of the medial septum at 5 to 50 Hz elicited a single brief milk ejection similar to natural reflex milk ejections, whereas prolonged low frequency stimulations (5 to 10 Hz) induced a prolonged inhibition of the reflex. In acute experiments under anaesthesia, lesions of the medial septum did not impair the amplitude and pattern of reflex milk ejections. In chronic experiments, lesions of the medial septum resulted first in a loss of body weight of the mothers and a parallel reduction in growth of the litters. After a few days, the litters gained weight normally, and the pattern of milk ejections was normal. Thus, the pathways which pass through or originate from the medial septum and which are excitatory for oxytocin release appear not to be involved in the regulation of the milk ejection reflex. In view of these results and those from our previous study on the lateral septum, we conclude that the whole septum is not essential to the milk ejection reflex. However, the effects of septal stimulation suggest that the medial and lateral septum may be involved in a secondary neural circuitry that can inhibit the reflex.

High-frequency septal stimulation suppresses long-term potentiation (LTP) in the CA1 region of rat hippocampus

The effects of high-frequency stimulation (HFS) of the medial septum/diagonal band (MSDB) on long-term potentiation (LTP) of CA1 extracellular field potentials were assessed in anesthetized rats. Ten rats received HFS of the Schaffer collateral pathway alone, and 10 received MSDB HFS 10 min prior to hippocampal HFS. Septal HFS suppressed LTP development assessed by change in population spike (PS) amplitude 60 min after hippocampal HFS (ANOVA, P < 0.03). Septal inhibition of LTP development was most prominent when septal HFS had little direct effect on the CA1 PS. These results provide a novel demonstration of the functional heterogeneity of septihippocampal pathways and in vivo modulation of hippocampal LTP by HFS of natural afferent inputs.

Luteinizing Hormone Release in the Anesthetized Cat following Stimulation in the Diagonal Band of Broca, Dorsal Septum and Fornix

The release of luteinizing hormone (LH) in response to electrical stimulation of septal nuclei (the diagonal band of Broca, DBB, and dorsal septal nucleus) and the subcallosal fornix has been studied in gonadectomized female cats. The cats were anesthetized with Althesin. Electrodes were placed on the medial and lateral aspects of the subcallosal fornix and paired bipolar stimulating electrodes were aimed at the DBB or dorsal septal nucleus. The effect of electrical stimulation of these regions on the secretion of LH was studied by radioimmunoassay of LH in serial blood samples taken before, during and after stimulation. Stimulation in the DBB or in the dorsal septal nucleus resulted in a peak of LH release during stimulation followed by further spontaneous peaks. All peaks showed an exponential decline. The frequency of spontaneous peaks following stimulation could reach the level found in unanesthetized cats. Stimulation of the subcallosal fornix produced a significant depression in the amplitude of LH release. The effects of DBB, dorsal septal and fornix stimulation are all exerted, we suggest, by projections to LHRH containing neurons in the preoptic region.

Stimulation of the lateral septum is a more effective conditioned stimulus than stimulation of the medial septum during classical conditioning of the eye-blink response.

Eight rabbits were trained in the classically conditioned eye-blink response procedure using stimulation of the septal nuclei as the conditioned stimulus (CS). Each rabbit was trained with both medial septal stimulation and lateral septal stimulation. Stimulation of the medial septum was a far less effective CS than stimulation of the lateral septum. This effect may be due to the different roles of these two nuclei in classical conditioning. Conditioning using lateral septal stimulation as a CS is dependent on the cerebellar interpositus nucleus as is conditioning using peripheral and other brain stimulation CSs.