GABAergic septohippocampal neurons are not necessary for spatial memory

Abstract

The medial septum/vertical limb of the diagonal band of Broca (MSDB) provides a major input to the hippocampus and is important for spatial memory. Both cholinergic and GABAergic MSDB neurons project to the hippocampus, and nonselective lesions of the MSDB or transections of the septohippocampal pathway impair spatial memory. However, selective lesions of cholinergic MSDB neurons using 192-IgG saporin (SAP) do not impair or only mildly impair spatial memory. Previously, intraseptal kainic acid was found to reduce levels of glutamic acid decarboxylase, a marker of GABAergic neurons, but not to alter the levels of choline acetyltransferase, a marker of cholinergic neurons. The present study further characterized the effects of kainic acid on GABAergic MSDB neurons and examined the effects of intraseptal kainic acid on spatial memory. Saline, kainic acid, SAP, or the combination of kainic acid and SAP was administered into the MSDB of rats. Spatial memory was assessed in an eight-arm radial maze and a water maze. Kainic acid destroyed GABAergic septohippocampal neurons, but spared cholinergic neurons. SAP eliminated MSDB cholinergic neurons, sparing noncholinergic neurons. Coadministration of kainic acid and SAP destroyed GABAergic and cholinergic MSDB neurons. Acquisition of the radial maze task and performance on this task with 4-h delays were unimpaired by intraseptal kainic acid or SAP, but were impaired by coadministration of kainic acid and SAP. Acquisition of the water maze task was unaffected by intraseptal kainic acid, delayed slightly by SAP, and impaired severely by coadministration of kainic acid and SAP. These results provide evidence that kainic acid at appropriate concentrations effectively destroys GABAergic septohippocampal neurons, while sparing cholinergic MSDB neurons. Furthermore, lesions of the GABAergic septohippocampal neurons do not impair spatial memory. While lesions of cholinergic MSDB neurons may mildly impair spatial memory, the combined lesion of GABAergic and cholinergic septohippocampal neurons resulted in a memory impairment that was greater than that observed after a selective lesion to either population. Thus, damage of GABAergic or cholinergic MSDB neurons, which together comprise the majority of the septohippocampal pathway, cannot totally account for the spatial memory impairment that is observed after nonselective lesions of the MSDB.

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

“…IBO injections preferentially destroyed 43% of PARV neurons but also nonsignificantly decreased cholinergic neurons (21%) in the caudal BF, and significantly decreased cortical AChE staining by 41%. The preferential loss of noncholinergic over cholinergic BF neurons after IBO injections corroborates previous reports (Burk and Sarter, 2001;Pang et al, 2001). This is the first study to show that IBO lesions of the NBM/SI did not affect spontaneous sleep-wake states, whereas 192IgG-SAP lesions had a transient effect.…”

“…An additional group of 20 rats received unilateral injections of IBO (8 g in 0.5 l of ACSF; IBO-UNI; n ϭ 11) or ACSF (0.5 l; ACSF-UNI; n ϭ 9). The IBO concentrations were chosen based on previous studies (Buzsaki et al, 1988;Cahill and Baxter, 2001;Pang et al, 2001) and a pilot study using a lower concentration of IBO (0.8 g in 0.5 l of ACSF), which did not yield significant lesions. For 192IgG-SAP, a pilot study was conducted to determine an effective amount histologically, and this amount from the same batch of immunotoxin was used for the main study.…”

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

“…The combined findings that fornix lesions impair memory and that selective cholinergic and GABAergic septal lesions do not raise the possibility that combined damage to cholinergic and noncholinergic septal projection neurons might be necessary to impair hippocampaldependent memory. In support of this, selective lesions of the septal GABA projection do impair memory when combined with 192 IgG-saporin lesions of the cholinergic projection (Pang et al 2001).…”

“…Some studies have reported significant impairment in spatial learning and memory following selective 192 IgG-saporin lesions of the MS/VDB (Shen et al 1996;Walsh et al 1996;Pang et al 2001;Cassel et al 2002;Lehmann et al 2002aLehmann et al ,b, 2003. However, the interpretation of these deficits as consequent to selective loss of cholinergic MS/VDB neurons is sometimes questionable.…”

“…Ibotenic acid lesions of the MS/VDB, which primarily affect the septal GABA neurons but spare the ACh neurons, impair place learning (Cahill and Baxter 2001). In contrast, selective kainic acid-induced lesions of the septohippocampal GABA projection do not impair spatial learning, suggesting that the septal GABAergic projection is also not necessary for memory (Pang et al 2001). The discrepancy between the effects of GABA lesions in these latter two studies may be related to the presence of damage to the peptidergic component of the septohippocampal projection, which was not assessed.…”