Gilberto N.O. Brito

Memory and the septo-hippocampal cholinergic system in the rat

This study examined the effects of intrahippocampal injections of scopolamine (a muscarinic antagonist drug) on performance of a working-memory task (contingently) reinforced T-maze alternation) and a reference-memory task (visual discrimination) by the same rats in the same maze. Rats in the first shipment were trained in delayed alternation, received bilateral implantation of cannulae aimed at the CA3 field of the dorsal hippocampus, and were tested for retention with 1 μl microinjections of scopolamine (35 μg) and saline on alternate days. These rats were then trained on visual discrimination and tested alternately under scopolamine or saline as described above. It was found that scopolamine impaired performance of delayed alternation to a greater extent than performance of visual discrimination. Data from rats in the second shipment replicated this finding, with the order of the tasks reversed, and, additionally, showed that delayed alternation, but not visual discrimination, was impaired at a dose of 12 μg/μl. A dose of 4 μg/μl had no effect on either task. It is concluded that performance of a workingmemory task is significantly more sensitive to disruption of cholinergic mechanisms in the hippocampus than performance of a reference-memory task.

Prelimbic cortex, mediodorsal thalamus, septum, and delayed alternation in rats

SummaryRats were trained preoperatively on contingently reinforced delayed alternation in a T-maze. Then different matched groups of rats received lesions in the prelimbic cortex, mediodorsal thalamus, posterodorsal septum (aimed at transecting the precommissural fornix), and control operations (no brain lesions). Following a 2-week recovery period the rats were retested in the T-maze for retention of delayed alternation. Control rats were unaffected by the control operations and the testing hiatus of the recovery period. Rats with lesions in the prelimbic cortex performed at chance levels on the first postoperative session as did rats with posterodorsal septal lesions, but both groups recovered with continued experience, i.e., they could relearn the task. Rats with lesions in mediodorsal thalamus were only slightly affected by the lesions, The results suggest that a restricted field in the medial pregenual cortex, the prelimbic area, is critically involved in T-maze alternation. However, the data also suggest that a major subcortical source of afferents to prelimbic cortex, the mediodorsal nucleus of the thalamus, is not crucial for retention of delayed alternation. Impairment in retention of contingently reinforced T-maze delayed alternation following interference with septo-hippocampal circuitry is consistent with data previously reported.

Behavioral characteristics of vasopressin-deficient rats (Brattleboro strain).

A group of vasopressin-deficient rats (Brattleboro strain--DI) and a group of normal Long-Evans rats were successively evaluated on visual discrimination, olfactory discrimination, delayed alternation at short and long intertrial intervals (ITIs), approach-avoidance conflict in a straight runway, and open-field behavior. It was found that DI rats adapted more slowly than normal rats in the T-maze, in the straight runway, and they were slower to emerge into the open field. The DI rats were impaired relative to normal animals on the discrimination tasks (visual and olfactory), but they were not impaired on delayed alternation (at least for short ITIs). DI rats also showed better retention of the punishment effect in the approach-avoidance conflict test than normal animals. It is suggested that DI rats have defective reference-memory mechanisms, fairly intact working-memory processes and altered adaptability (timidity or cautiousness).

T-maze alternation, response patterning, and septo-hippocampal circuitry in rats ☆

The effects of small electrolytic lesions in the posterodorsal septal area (aimed at the precommissural fornix) on acquisition and retention of either a spatio-temporal task (contingently reinforced T-maze alternation) or a temporal task (response patterning in a straight runway) were investigated in Long-Evans rats. Acquisition of T-maze alternation was impaired following posterodorsal septal lesions, but with extensive training there was evidence of learning. Postoperative retention of T-maze alternation was also impaired by posterodorsal septal lesions but, again, with continued practice the experimental animals relearned the task and came to perform as well as controls. Postoperative acquisition of response patterning in a runway was significantly but not greatly impaired by posterodorsal septal lesions. The experimental animals did pattern, but not as well as controls, even after substantial practice. Retention of response patterning was severely impaired following lesions in the posterodorsal septum but, as in the T-maze task, experimental animals improved significantly in performance with postoperative practice. The results were interpreted in the light of two recent formulations of the functions of the septo-hippocampal system: cognitive mapping and working memory. However, the data are not conclusive and suggest that inhibition theories of septo-hippocampal function are possibly relevant.

The behavior of vasopressin-deficient rats (Brattleboro strain) ☆ ☆☆

Seven Brattleboro rats homozygous for diabetes insipidus (DI) and seven normal Long-Evans (LE) rats were tested on a neuropsychological test battery comprised of the following tasks: time-spent-eating in two adaptation boxes, time-to-emerge into an open field, adaptation to a T-maze, contingently reinforced T-maze alternation, olfactory and visual discrimination, runway learning, approach-avoidance conflict, step-through passive avoidance, prod burying, and stress-induced interference. It was found that DI rats adapted more slowly than LE rats to novel environments (e.g., adaptation box, T-maze, and runway), and DI rats were slower to emerge into an open field. However, DI rats performed as well as LE rats on all other tasks. These results suggest that DI rats have altered temperamental dispositions (timidity or cautiousness), normal working and reference memory, and similar susceptibility (compared to LE rats) to the interfering effects of inescapable stress.

Medial septal nucleus and delayed alternation in rats

The effects of small electrolytic lesions in the medial septal region on retention of a spatiotemporal task (contingently reinforced T-maze alternation) were determined in Long-Evans rats. With brief intertrial intervals (massed trials), control rats were only slightly (if at all) affected by the 17-day vacation from testing during the period of postoperative recovery.The experimental rats with medial septal lesions, on the other hand, dropped to chance levels of alternation and then recovered to a statistically significant but slight amount over nine sessions of postoperative testing. With long intertrial intervals produced by running the animals in squads of four, control rats dropped to chance levels of alternation and then recovered somewhat over seven additional sessions of testing. Animals with septal lesions tended to perseverate and showed no evidence of recovery. Results were interpreted to indicate that a major hippocampal afferent system (dorsal fornix) plays a crucial role in mediating the spatiotemporal construction and use by the brain of the “cognitive maps” necessary for successful T-maze alternation.

Septo—hippocampal disconnection and Go—NoGo discrimination in rats

Rats were trained preoperatively to perform a Go—NoGo discrimination task in sensorially distinct parallel runways. Rats with posterodorsal septal lesions, which substantially disconnected the septum from the hippocampus, when tested 2 weeks postoperatively, ran significantly more slowly on the S+ (Go) trials and faster on the S− (NoGo) trials on the first postoperative session compared with the last preoperative session. Performance of rats without brain lesions was unaffected by the control surgery and recovery period. During six subsequent postoperative relearning sessions, group differences tended to attenuate on S+ trials, but rats with posterodorsal septal lesions persisted in running faster than controls on S− trials. The results could be considered consistent with inhibition hypotheses of septo—hippocampal function. The data are not consistent with the view that the septo—hippocampal system is involved exclusively in working memory.