Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin

Abstract

In this study, we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study was, however, relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is, by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data do support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, they further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's disease.

Aversive stimulus attenuates impairment of acquisition in a delayed match to position T-maze task caused by a selective lesion of septo-hippocampal cholinergic projections

“…This demonstrates that a mild aversive stimulus can attenuate or mask a deficit resulting from lesion of MS cholinergic neurons on acquisition of a spatial task. This is consistent with studies of working memory which used paradigms with an aversive component and that found that selective cholinergic lesions of the MS did not produce acquisition deficits in spatial working memory [4,5,16]. Notably, application of the aversive stimulus had no significant effect on DMP acquisition in the non-lesioned controls.…”

“…Other investigations, though, have reported only limited effects of MS SAP lesions in other spatial tasks. For example, Dornan et al [16] reported that a selective reduction of cholinergic transmission in the basal forebrain was by itself insufficient to account for the functional impairments in spatial learning of rats using a Morris water maze (MWM) paradigm. Baxter et al [4,5], also utilizing a MWM task, reported similar findings.…”

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation

“…Indeed, for some investigators cholinergic lesions did not cause impairment in spatial memory (15,23). Spatial memory, determined by the MWM, has been associated with LTP in mice in vivo (5).…”

“…These studies have given inconsistent results concerning the cognitive and behavioral processes that are affected by altering cholinergic transmission (12,15,16). This is likely related to the fact that in many cases both noncholinergic and cholinergic projection neurons are destroyed, or that the lesions produced do not fully deplete cholinergic neurons.…”

“…This is likely related to the fact that in many cases both noncholinergic and cholinergic projection neurons are destroyed, or that the lesions produced do not fully deplete cholinergic neurons. Moreover, most immunolesion experiments were performed initially in rats (15,16), and only recently immunotoxins have been developed for mice (11), a species in which genetic tools are available. In mice these toxins show poor selectivity depending on the dose used (11).…”