Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments

Abstract

The functional contribution of nucleus basalis magnocellularis (NBM) and the medial septal area (MSA) to memory was evaluated in two different spatial discriminations. Preoperatively, rats were trained to a criterion level of performance in a simultaneous left/right discrimination on the stem of a T-maze (a trial-independent memory) and a discretetrial, rewarded alternation discrimination on the arms of the T-maze (a trial-dependent memory). Bilateral lesions were made by injecting ibotenic acid (IBO) into the NBM, MSA, both NBM and MSA, or dorsal globus pallidus (DGP), and by radiofrequency current (RF) in the NBM and MSA. Control rats received operations in which either no current was passed or no neurotoxin was injected. Lesions in the NBM, MSA, or both the NBM and MSA produced a similar pattern of behavioral changes relative to the performance of controls; postoperative reacquisition of the arm discrimination was initially impaired but showed recovery to normal levels, whereas postoperative reacquisition and reversal of the stem discrimination was not impaired (except following the combined NBM and MSA lesion). Lesions of the DGP had no effect on choice accuracy in any discrimination.When the discrimination on the arms was made more difficult by increasing the delay interval during which the information had to be remembered, rats with combined NBM and MSA lesions were again impaired relative to controls and showed no signs of recovery of function. These results provide information about the behavioral functions of the basal forebrain cholinergic system and suggest that pathological changes in certain components of this system can cause disorders of memoryWithin the basal forebrain of the rat is a core of acetylcholinergic (ACh) neurons (Sofroniew et al., 1982) (NBM), diagonal band of Broca, and the medial septal area (MSA) Lehmann et al., 1980;Johnston et al., 1981;Bigl et al., 1982;Hartgraves et al., 1982; Pearson et al., 1983; Saper, 1984). The NBM projects ACh afferents primarily to the neocortex, and the MSA and vertical limb of the diagonal band project ACh afferents primarily to the hippocampus. The frontal neocortex and hippocampus, and the cholinergic systems afferent to these areas, have an important role in memory (Bartus, 1980; Bartus et al., 1982; Mishkin, 1982). Recently, the behavioral effects of lesions produced in either the NBM (LoConte et al., 1982; Flicker et al., 1983) or MSA (Mitchell et al., 1982) have been evaluated separately in individual tasks, but the behavioral effects of these two lesions have not been compared on the same tasks.In the present study, both ibotenic acid (IBO) and radiofrequency (RF) current were used to produce lesions. IBO causes degeneration of neuronal perikarya at the site of injection, without damaging axons of passage or neurons distant from the injection site (Coyle and Schwartz, 1983). RF lesions destroy both neuronal perikarya and fibers of passage. The comparison of RF and IBO lesions allows for the assessment of the relative importance of d...

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

“…Lesions of the fimbria-fornix, or electrolytic or neurotoxic lesions of the medial septum, impair hippocampal-dependent learning and memory (Mahut 1972;Olton et al 1978;Mitchell et al 1982;Rawlins and Olton 1982;Hepler et al 1985;Kelsey and Landry 1988;Markowska et al 1989;Kelsey and Vargas 1993). These studies have been interpreted as supporting the hypothesis that hippocampal ACh is necessary for normal memory function.…”

Age-Related Changes of Cholinergic Markers in the Rat Brain

“…Numerous neurochemical studies using both animals and humans have revealed age-related changes in neu rotransmitter enzyme activities and receptor binding (1)(2)(3)(4). Age-related memory disorders, including Alzhei mer's disease, show a substantial decrease in cholinergic markers, such as choline acetyltransferase (ChAT), acetyl cholinesterase (AChE) and the number of muscarinic receptors (mAChR), in the hippocampal formation and other cortical and basal forebrain structures (5-9).…”

Working Memory Deficit in Aged Rats in Delayed Nonmatching to Position Task and Effect of Physostigmine on Performance of Young and Aged Rats.

“…Ibotenic acid lesion of the nucleus basalis and/or medial septum, which include a num ber of cholinergic neurons projecting to the cortex and hippocampus, respectively, has been reported to produce a decrease in choice accuracy using this T-maze alternation task (19,(22)(23)(24). A similar memory decline was observed in rats that received an intracer ebroventricular injection of AF64A, a cho linergic neurotoxin (25).…”