Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: Role of cholinergic medial septal neurons in spatial working memory.

Abstract

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory.

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

“…It means only that elevating ACh is sufficient to overcome the deficit, perhaps, for example, by increasing compensatory responses (Björklund and Dunnett 1995). Indeed, the hypothesis that septal GABA receptor activation impairs memory exclusively via an effect on hippocampal ACh is not supported by the finding that septal infusions of muscimol still impair memory when the septohippocampal cholinergic projection is lesioned (Pang and Nocera 1999). On the other hand, a wealth of evidence indicates that septal GABA receptor activation does likely impair memory through a process that involves, at least in part, inhibition of hippocampal ACh.…”

“…Impairments have also been reported in acquisition and performance of a delayed matching-to-place task in the T-maze (Gibbs 2002;Johnson et al 2002) following lesions limited to MS/VDB cholinergic neurons. However, nonmatching-to-place in the Tmaze is not impaired following MS/VDB cholinergic lesions (Pang and Nocera 1999;Kirby and Rawlins 2003). Because the memory requirement in the two tasks is equivalent, the matching deficits may reflect an inability to apply a behavioral rule that is contrary to the rat's spontaneous nonmatching behavior, rather than an impairment in spatial memory per se.…”

“…This distinction between necessity and sufficiency/ involvement is hardly a novel one (e.g., Berntson et al 1996;Martin et al 2000), but it has not been widely considered in analyses of the role of septohippocampal ACh in memory (cf. Pang and Nocera 1999;Baxter and Murg 2002;McIntyre et al 2002).…”

“…For instance, septal infusions of cholinergic agonists enhance memory or reverse memory deficits (Izquierdo et al 1992;Givens and Olton 1995;cf. Markowska et al 1995;Pang and Nocera 1999), and would thus be expected to increase ACh function in the hippocampus. Instead, septal infusions of cholinergic agonists decrease hippocampal extracellular ACh levels (Gorman et al 1994).…”

Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

“…However, a recent study in which cholinergic neuron integrity at the lesion site was verified found impairment in spatial working memory after 192 IgGsaporin lesions of the MS/VDB (Lehmann et al 2003), suggesting that these lesions can be sufficient to impair spatial memory under some circumstances. Studies examining spatial working memory using rewarded T-maze alternation have not found effects of cholinergic MS/VDB lesions (Pang and Nocera 1999;Kirby and Rawlins 2003). These differences across studies also do not appear to be related to whether the lesion is given before training on the maze task, or afterward.…”