J. N. P. Rawlins

Septo-hippocampal connections and the hippocampal theta rhythm

SummaryRecordings were made of spontaneous hippocampal theta activity in free-moving rats, before and after a variety of lesions. Three recording sites were used to monitor activity in the dorsal hippocampus, the ventral hippocampus, or close to the site of the hippocampal flexure. Electrolytic lesions were made in the medial septal area or the dorso-lateral septal area; surgical transections were made of the fimbria or dorso-medial area of the fornix. Following lesions restricted to the medial septal area, theta was abolished throughout the hippocampus; after lesions restricted to the dorso-lateral septal area theta was retained. Fimbria lesions abolished theta in the ventral, but not the dorsal hippocampus; dorso-medial fornix lesions abolished it in the dorsal, but not the ventral, hippocampus. In some subjects the hippocampal formation was subsequently stained for cholinesterase: cholinesterase staining loss was generally associated with theta loss, but this was not clear at the flexure recording site. It was confirmed that theta is dependent upon the integrity of the medial septal area. It was concluded that damage to hippocampal afferents from the septum does abolish theta, while damaging the feedback efferents does not.

The hippocampus and conditioning to contextual cues.

Two experiments are reported in which behavioral control by contextual cues was assessed in groups of rats with dorsal hippocampal (HC), neocortical (NC), or operated control (OC) lesions. Following Odling-Smees (1975) procedure, a Pavlovian conditioning paradigm was followed in which conditioned stimuli (CSs: tone, light) predicted an unconditioned stimulus (US:footshock) always, never, or half the time. Conditioning trials took place in a small black box. Subsequently, conditioning to background contextual cues was assessed by measuring the amount of time rats spent in the black box in preference to an adjacent white one with neither CS nor US presented. In OC groups and, to a lesser extent, NC groups, conditioning to background cues was inversely related to the probability that CS predicted US. In contrast to graded contextual conditioning in control groups, the HC groups consistently showed abnormally strong conditioning to context that was at or near asymptotic level. The results, which were related to current theories of the relation between contextual stimuli and CSs, suggest that the hippocampus may play an important role in stimulus selection during learning.

The effects of hippocampectomy and of fimbria section upon the partial reinforcement extinction effect in rats.

SummaryRats were trained to run in an alley for food reward given on every trial (continuous reinforcement, CR) or on a random 50% of trials (partial reinforcement, PR) and were then extinguished. Sham-operated controls showed the usual partial reinforcement extinction effect (PREE), i.e., PR-trained animals were more resistant to extinction than CR-trained animals. The PREE was abolished by hippocampectomy, which increased resistance to extinction in CR-trained rats and decreased it in PR-trained rats. Bilateral fimbria section had no effect on resistance to extinction in either condition. These results are discussed in the light of theories of hippocampal function and the anatomy of septohippocampal connections.

Differential involvement of the shell and core subterritories of the nucleus accumbens in latent inhibition and amphetamine-induced activity

Latent inhibition (LI) consists of retardation in conditioning to a stimulus as a consequence of its prior non-reinforced pre-exposure. In view of findings that LI is disrupted in acute schizophrenic patients and evidence from animal experiments pointing to the involvement of the mesolimbic dopamine (DA) system in this phenomenon, the present study investigated the effects of electrolytic lesions to the shell and core subterritories of the nucleus accumbens on LI in rats (Expt. 1). LI was indexed by the amount of suppression of drinking in the presence of a tone that was either pre-exposed or not prior to its pairing with reinforcement (a foot shock). Expt.2 tested the effects of the DA antagonist, haloperidol, on LI in shell- and core-lesioned animals. Expt. 3 tested the effects of shell and core lesions on spontaneous and amphetamine-induced locomotion. In Expt. 1, LI, i.e., lower suppression of drinking in the pre-exposed as compared to the non-pre-exposed animals, was obtained in the sham-operated condition. Core and shell lesions produced distinct effects on LI. Animals with core lesions developed LI, but exhibited an overall lower suppression of drinking in comparison to the sham-operated animals. In contrast, shell lesions led to a disappearance of LI. Expt. 2 replicated the differential effects of shell and core lesions on LI, although in this experiment, core lesion did not attenuate suppression of drinking. Haloperidol prevented shell-induced abolition of LI. In Expt. 3, shell- but not core-lesioned animals were more active than sham controls following amphetamine administration. These results provide evidence for functional differences between the shell and core subregions, as well as for the involvement of the mesolimbic DA system in LI.

Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats

Rats with radiofrequency lesions of the fimbria/fornix or with extensive aspiration lesions of the hippocampal region (the hippocampus proper, dentate gyrus, and subicular complex) were tested on their performance of a delayed non-matching to position task which had been learnt before surgery. On a given trial, one of two sample levers was presented in a random manner. Following a response on this lever and a subsequent delay, both levers were presented and reward was now contingent on a response on the lever that was not used as the sample. Both lesions produced equivalent performance deficits on this test of spatial working memory, the pattern of these deficits being consistent with a mnemonic impairment. The lack of difference between these two groups on a variety of performance measures indicates that hippocampal connections passing through the fornix are not only necessary for this test, but that non-fornical hippocampal connections appear unable on their own to maintain accurate responding.

Latent inhibition in rats is abolished by NMDA-induced neuronal loss in the retrohippocampal region, but this lesion effect can be prevented by systemic haloperidol treatment

Latent inhibition (LI) refers to the retardation in learning about the significance of a neutral stimulus that results from its nonreinforced preexposure. There is evidence that electrolytic or aspiration lesions of the hippocampal formation can disrupt LI (see I. Weiner, 1990). It has been suggested that this effect may stem from the interruption of a projection from the retrohippocampal region to the nucleus accumbens (A. J. M. Clark et al., 1992). The present experiment assessed this possibility by comparing LI in rats with retrohippocampal N-methyl-D-aspartate (NMDA) lesions extending from the entorhinal cortex to the ventral subiculum to that seen in vehicle controls and unoperated controls. LI was abolished by the retrohippocampal lesion. The effect of the lesion on LI was prevented by treatment with systemic haloperidol (0.2 mg/kg). The results are discussed with respect to an animal model of schizophrenia.

Effects of Amygdaloid and Amygdaloid-Hippocampal Lesions on Object Recognition and Spatial Working Memory in Rats

Neurotoxic lesions of the amygdala did not affect the postoperative acquisition of a nonspatial test of object recognition (delayed nonmatching to sample) even when retention delays were increased from 0 s to 20 or 60 s, or when test stimuli were deliberately repeated within a session. Although these amygdaloid lesions did not alter forced-choice spatial alternation, they slightly increased neophobic responses to novel foods and environments. In contrast, combined amygdalohippocampal (A + H) lesions impaired performance on the object recognition task when the retention intervals were increased beyond 0 s and when test stimuli were repeated within a session. The A + H rats were also severely impaired on the spatial alternation task, and they showed reduced neophobia. Comparisons with a previous study show that damage to the amygdala or hippocampus does not affect object recognition, whereas A + H damage produces clear deficits.

Critical determinants of nonspatial working memory deficits in rats with conventional lesions of the hippocampus or fornix.

Rats with conventional lesions of the hippocampus or fornix were compared postoperatively with controls on nonspatial memory tasks. Neither lesion impaired delayed matching-to-sample (DMS) performance in a discrete-trial task involving pseudo-trial-unique complex stimuli. An impairment emerged if a single pair of complex stimuli was used throughout each days session, and the greatest impairment was obtained with the use of a single pair of less complex stimuli throughout each days test. Transfer to a continuous DMS task with no explicit intertrial interval produced a different pattern because both lesion and control levels of performance were depressed when two complex stimuli were used repeatedly. A final, separate discrimination learning experiment showed that hippocampectomized rats readily discriminated between the stimuli associated with the greatest lesion-induced DMS deficit. Hippocampal dysfunction thus produces clear deficits on non-spatial memory tasks under appropriate test conditions.

Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat

SummaryRats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.

The hippocampus, collateral behavior, and timing.

Rats with hippocampal lesions (HC), cortical control lesions, or sham operations were trained to lever press on a differential reinforcement of low rates (DRL) schedule requiring 12 sec between responses. In four experiments, factors affecting performance efficiency in this paradigm were manipulated. Providing extra opportunities for collateral mediating behavior (Experiment 1) aided all groups nondifferentially. Adding a limited hold (Experiment 2) or administering chlordiazepoxide HCl (Experiment 3) reduced DRL efficiency in all groups nondifferentially. However, adding an auditory stimulus marking the halfway point in the DRL requirement (Experiment 4) differentially aided the HC group. The implications of these findings for different theories of hippocampal function are discussed.