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L E Jarrard

Publications and source records attributed to L E Jarrard.

51 records · Page 3Linked to original sources

Non-cholinergic neurotoxic effects of AF64A in the substantia nigra.

Ethylcholine aziridinium ion (AF64A), a putative specific cholinergic neurotoxin, was unilaterally injected into the substantia nigra of male rats. One week following injection, rats that were challenged with apomorphine exhibited ipsilateral circling behavior. After two weeks, rats were sacrificed and corpus striatum and combined n. accumbens plus o. tubercle were assayed for dopamine. Striatal dopamine levels were depleted by 50%. Histological examination showed that AF64A caused extensive damage at the injection site. These data indicate that injection of AF64A into the substantia nigra can result in damage to dopaminergic neurons.

Animals↗

Biochemical indices of reactivity and habituation in rats with hippocampal lesions.

The response of rats with hippocampal lesions to acute and repeated footshock stress was assessed by measurement of pituitary cyclic AMP, plasma corticosterone and plasma prolactin. Levels of pituitary cyclic AMP and plasma prolactin and corticosterone were similar in never-shocked sham controls, and never-shocked hippocampal and neocortical lesion groups. Acute first time shock markedly elevated all measured stress indices with no statistically significant differences observed among surgical groups. In rats subjected to repeated stress (one 15 min footshock session per day for 10 days) and sacrificed 24 hours after the last shock session, levels of pituitary cyclic AMP and plasma hormones were similar to levels in never-shocked shams with the exception of the hippocampal animals. The rats with hippocampal lesions had higher levels of pituitary cyclic AMP, plasma corticosterone and plasma prolactin compared to never-shocked animals. We suggest that these data reflect a hyperreactive response of the hippocampal animals to a situation previously associated with shock. Finally, rats in all surgical groups subjected to repeated stress and sacrificed immediately after the last shock session showed a diminished cyclic AMP response to the stressor as compared to first footshock session response, demonstrating a habituation to the stressor as measured by this index. No differences in habituation were observed among hippocampal, neocortical and sham groups. Plasma hormone responses did not habituate in any group. These data support the behavioral observations of hyperreactivity in hippocampal animals and indicate that hippocampal animals are able to habituate to repeated stressful stimuli.

Animals↗

Behavioral and neurochemical effects of intraventricular AF64A administration in rats.

Ethylcholine aziridinium ion solution (AF64A), a putative specific cholinergic neurotoxin, was injected bilaterally into the lateral ventricles of rats. Following administration of 3 or 6 nmoles of AF64A, drinking and eating were depressed but returned to normal levels after several days; increased activity in the 6 nmole group persisted throughout the 21 days of observations. Performance on complex place and cue tasks indicated that injected animals were impaired in reference memory only on the place task, but working memory was impaired on both tasks. Neurochemical measurements in a separate group of animals one week after AF64A injections found large depletions of acetylcholine in hippocampus and corpus striatum, but not depletions of norepinephrine (hippocampus) or dopamine (striatum). Histological examination of the injection site revealed extensive damage to the fimbria-fornix similar to that seen after electrolytic lesions. Since the behavorial and neurochemical changes are similar to those previously found following fimbria-fornix lesions, it is concluded that the present results are possibly due to non-specific lesion effects of the neurotoxin rather than a specific effect on cholinergic systems.

Acetylcholine↗

On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus.

Behavioral changes following interruption of the main connections of hippocampus and closely related areas (entorhinal cortex, mammillary bodies, dentate gyrus) were determined and compared with findings of previous research that involved direct damage to hippocampus. By a within-subjects design, rats were trained to run in a radial maze with a procedure that involved two kinds of learning (place and cue) and two memory functions (working and reference memory). Rats with fimbria-fornix and entorhinal cortex lesions were impaired on both the place and the cue task. Specifically, the animals suffered a general impairment in working memory on both tasks but were impaired in reference memory only on the place task. Animals with lesions of the dentate gyrus and mammillary bodies were able to perform the complex place and cue tasks with minimal problems. In previous research it was found that direct damage to hippocampus (including all cell fields, alveus, fimbria) resulted in impaired performance only on the place task (Jarrard, 1983). Taken together, these findings indicate that interruption of hippocampal input/output pathways and/or damaging some closely related structures has a greater effect on the behaviors studied than does direct damage to hippocampus.

Animals↗

Selective hippocampal lesions and behavior: effects of kainic acid lesions on performance of place and cue tasks.

Kainic acid (KA) lesions were used to study the effects of damage to the CA3 cell field and subiculum on performance of complex place and cue tasks. In Experiment 1, neuroanatomical techniques were employed to determine the selectivity of the lesions. In a within-subjects design, rats in Experiment 2 were trained before the operations to run on an eight-arm radial maze with procedures that involved two kinds of learning (place and cue) and two memory functions (reference memory and working memory). Interrupting the intrahippocampal circuit by damaging the CA3 cell field with KA had minimal effects on performance; injections into subiculum and complete aspiration lesions of hippocampus resulted in impairments on the place but not the cue task. Only intraventricular injections of KA affected performance on both tasks. These results fail to support either the cognitive map or the working memory theory of hippocampal function. The presence of distant damage beyond the immediate area of injection complicates interpretation of the results and may serve to limit the usefulness of KA as a neurotoxin in behavioral investigations.

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Role of retroactive interference in the spatial memory of normal rats and rats with hippocampal lesions.

The importance of retroactive interference (RI) in memory for spatial locations was studied by using a 12-arm radial maze and a standard RI paradigm. Animals in the RI condition first learned to choose 4 of the 12 arms, followed by training to a second set of 4 arms. In the control condition for interference, rats learned the first set of arms but were not trained to approach the second set. Thereafter, animals in each interference condition were assigned to groups (hippocampal, cortical control, unoperated control), the operations were carried out, and then all animals were tested for retention of the set of arms learned first. Contrary to predictions of the cognitive map theory, O'Keefe & Nadel, 1978), RI was found in control animals. The severe memory deficit found in hippocampals was not influenced by the interference variable. In addition to impaired performance early in relearning, rats with hippocampal lesions continued to make many errors throughout the 10 wk of testing, including choices to unbaited arms and repeated entries into baited arms. However, hippocampals eventually learned not to reenter unbaited arms. These data indicate a deficit in the selection and utilization of sets of responses and are interpreted as implicating the hippocampus in retrieval processes.

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Selective hippocampal lesions: differential effects on performance by rats of a spatial task with preoperative versus postoperative training.

Animals with selective lesions involving different hippocampal cell fields and/or projections either learned a complex spatial maze postoperatively or were trained preoperatively and tested after the operations. Following damage to anterodorsal CA1 cells and the alveus, acquisition was impaired but performance was normal when the task was learned preoperatively; postoperative acquisition and performance of the preoperatively learned task were impaired in animals with fimbrial lesions. These data suggest that the CA1 cell field and the projections to the subiculum play an important role in the acquisition of new spatial information but that these connections are not necessary for the utilization of spatial information learned preoperatively.

Animals↗

Anatomical and behavioral analysis of hippocampal cell fields in rats.

For a study of the structure and function of the different hippocampal cell fields, a surgical approach was devised that permitted selective damage to either the hippocampal subdivisions or the major efferent projections. Neuroanatomical techniques were used in Experiment 1 to verify the selective nature of the lesions and to provide information concerning differential hippocampal projections. In Experiment, 2, rats with selective hippocampal lesions were tested on a series of tasks chosen to measure various aspects of behavior. Animals with fimbrial lesions interrupting connections between the CA3-CA4 cell fields and the septal region were similar to animals with extensive hippocampal lesions in being more active than the other groups at night, more active during the day, and more affected by deprivation. In addition, both groups were facilitated in acquisition of a shuttle box avoidance task. Extensive damage to the hippocampus and more selective damage to the CA1 pyramidal cell field resulted in impaired spatial reversal learning. The results are interpreted as providing support for the view that the two main subdivisions of the hippocampus, the CA1 and CA3-CA4 cell fields, are differentially involved in behavior.

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Role of interference in retention by rats with hippocampal lesions.

Involvement of the hippocampus in memory was studied in the rat by employing a retention task with and without interpolated activity. Rats with extensive damage to hippocampus were able to relearn a preoperatively acquired single-alternation task with savings and to perform the single alternation with relatively long delays at a level similar to that of control subjects. However, hippocampals were more affected than normals by an interpolated activity that interferes with retention. The finding of normal retention combined with increased susceptibility to interference supports the view that the memory impairment in subjects with damage to hippocampus may be due to an excess of interference among stored information.

Animals↗