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Biomedical subjects

D S Olton

Publications and source records attributed to D S Olton.

At least 19 recordsLinked to original sources

Galanin in the medial septal area impairs working memory.

Galanin, a peptide of 29 amino acids, is co-localized with acetylcholine in a subpopulation of neurons of the medial septal area (MSA) that project to the hippocampus. Galanin reverses the actions of acetylcholine in several biochemical and behavioral procedures, and may be involved in memory processes. To test the possibility that galanin acts on the cell bodies of MSA neurons, two measures of septohippocampal function were assessed following intra-septal microinfusion of galanin or two synthetic fragments of galanin (1-16 and 21-29). The behavioral measure was choice accuracy in a working memory task in a T-maze. The electrophysiological measure was hippocampal theta activity recorded from the dentate hilus. The galanin fragment, 1-16, and the complete peptide, 1-29, decreased choice accuracy and decreased hippocampal theta activity in a dose-dependent fashion. Saline and the 21-29 fragment had no effect on choice accuracy and hippocampal theta. Sensorimotor performance was unaffected. These findings demonstrate that galanin impairs working memory when administered directly into the MSA and suggest that galanin inhibits MSA neural activity.

Animals

Tolman's cognitive analyses: predecessors of current approaches in psychology.

Hindsight is always helpful. I hope that I have provided some appreciation of why the experiment by Tolman et al. (1946) is a classic and deserves to be included in this series. Evaluating the extent to which this particular experiment actually influenced the development of all of the endeavors described above is difficult, and I leave it to those individuals who have an interest in the history of science to draw the appropriate conclusions. Even without direct causality, the continued relevance of this experiment is striking. We might all wish that we have sufficient foresight to investigate significant problems in such a way that our own contributions are still considered important almost 50 years after we make them.

Animals

Hippocampus, fimbria-fornix, amygdala, and memory: object discriminations in rats.

Rats with lesions of the fimbria-fornix, hippocampus, or hippocampus and amygdala were tested in object discriminations commonly used with monkeys. Two 1-pair object discriminations were learned preoperatively and tested postoperatively. Additional postoperative testing included acquisition of a third 1-pair object discrimination, an 8-pair concurrent object discrimination, and spatial alternation. All lesions impaired performance in the 8-pair object discrimination and in spatial alternation but not in the 1-pair object discriminations. Data from this study and from previous studies indicate that the hippocampus in both rats and monkeys has an important role in the mnemonic processes required for concurrent object discriminations and that variations of the procedure for concurrent object discriminations can be an effective tool for investigating hippocampal function.

Amygdala

Circadian rhythm of luminance detectability in the rat.

Rats lived in a visual detection test environment which allowed for around-the-clock measurement of the detectability of a 500 nm stimulus of low luminance. Daily trends in visual sensitivity were compared with a behavioral activity measure, the rate of trial initiations in the self-paced testing procedure. Both variables showed circadian rhythms with periods exceeding 24 hr in the absence of day-night cues. However, the two oscillations were phase-displaced, such that maximal visual sensitivity occurred earlier than did maximal behavioral activity, each day. The temporal organization of visual sensitivity may underlie well-known photic influence on circadian rhythms and photoperiodic behavior.

Animals

Spatial memory deficit following fimbria-fornix lesions: independent of time for stimulus processing.

The present experiment examined the possible role of stimulus processing time in the spatial memory deficit found following fimbria-fornix lesions in rats. Rats were trained preoperatively on a radial arm maze in a procedure that placed them at the end of each arm and confined them there for 30 seconds. This confinement period was markedly longer than the few seconds the rats normally spend there in the usual test procedure. Rats with fimbria-fornix lesions performed no better than expected by chance on the first choice after placements. Although performance on subsequent choices was above chance, this was due to a strong turning pattern; when this pattern was interrupted, performance was no greater than that expected by chance on all choices. These data demonstrate that the deficit in the radial arm maze resulted primarily from a difficulty in spatial memory, rather than from an insufficient time for processing stimulus information.

Animals

Hippocampal connections and spatial discrimination.

Rats were tested in a new spatial discrimination procedure which measured working memory. Following preoperative testing, lesions were placed to disrupt each of the major extrinsic fiber connections of the hippocampal formation. Destruction of the entorhinal area, body of the fimbria-fornix anterior to hippocampus, septum, or postcommisural fornix produced a severe and consistent impairment in performance. Analysis of error patterns indicated that when animals with limbic lesions made errors, they were likely to make these errors in the same sequence as the original choices. These data support the hypothesis that the hippocampus has an important role in the processing of information about spatial location, and that normal performance on this task requires an intact hippocampal circuitry.

Acetylcholinesterase

The function of septo-hippocampal connections in spatially organized behaviour.

The role of septo-hippocampal connections in spatial behaviour is examined in lesion and stimulation experiments in rats. Destruction of septo-hippocampal connections produces a severe and enduring deficit in the ability to perform a spatial memory task. Furthermore, crossed unilateral lesions of the entorhinal area and fimbria-fornix produce the same deficit as bilateral lesions in either the entorhinal area or the fimbria-fornix, as predicted from a disconnection analysis of hippocampal lesions. Evidence also suggests that septo-hippocampal damage produces a greater deficit in spatial behaviours when a flexible response is required than when a consistent response is required, although this difference is a relative one rather than an absolute one. Finally, disruptive stimulation of the hippocampus while rats are performing a spatial memory task produces retrograde amnesia but not proactive interference. Taken together, these data indicate an important role of the septo-hippocampal system in spatial behaviour, and in the maintenance of spatial memories.

Animals

Damage to hippocampus and hippocampal connections: effects on DRL and spontaneous alternation.

Male albino rats were tested both pre- and postoperatively either on a schedule of differential reinforcement of low-rate responding (DRL 20 sec; Experiment 1) or for spontaneous alternation (Experiment 2). Selective lesions were produced in the hippocampus and its fiber connections. Performance of both behaviors was consistently disrupted by total fornix, medial fornix, and septum lesions, while neither behavior was significantly disrupted by postcommissural fornix or entorhinal cortex lesions. Anterior hippocampus lesions consistently disrupted only DRL performance, while neither posterior hippocampus nor lateral fornix lesions resulted in consistently impaired performance of either behavior. These data are discussed as representing a possible functional differentiation between anterior and posterior portions of the hippocampal system.

Animals

Spatial memory.

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Action Potentials

Active avoidance and brain DNA after postnatal food deprivation in rats.

Fond deprivation was produced in infant rats, from 2 to 20 days of age, by a procedure designed to minimize reduction in maternal care. Body weights in the deprived animals were 60% of control weights at 7 days, 65% at 20 days, and, after ad lib feeding, 89% at 4 months. No change was observed in the rate of acquistion of a conditioned active avoidance response in the food-deprived rats when compared with their littermate controls when tested as adults. No lasting reduction in cerebral desoxynucleic acid (DNA) was observed despote a 9% reduction in cerebellar DNA.

Animals

Hippocampal influence on hyperreactivity induced by septal lesions.

Rats were tested for their responses to 4 stimuli in order to measure hyperreactivity. Animals with septal lesions emitted the expected hyperreactivity. Lesions of the postcommisural fornix, precommissural fornix, or anterior hippocampus, administered 16 days prior to a septal lesion, blocked the expected hyperreactivity. Lesions localized to the medial or the lateral fibers of the fornix decreased the magnitude the duration of the expected hyperreactivity following septal lesions but did not block it. Lesions of the posterior hippocampus-entorhinal cortex had no reliable effect on the expected hyperreactivity after septal lesions. These data indicate that the appearance of hyperreactivity following a septal lesion depends upon a circuit involving the septum, precommissural fornix, anterior hippocampus, postcommissural fornix, and hypothalamus, and document an important functional relationship between the septum, anterior hippocampus, and hypothalamus.

Animals