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Published on: April 24, 2009
GABAergic septohippocampal neurons are not necessary for spatial memory
K C Pang1, R Nocera, A J Secor
1Department of Psychology, J.P. Scott Center for Neuroscience, Mind and Behavior, Bowling Green State University, Ohio 43403, USA. kpang@bgnet.bgsu.edu
Insights
GABAergic septohippocampal neurons do not impair spatial memory. Combined GABAergic and cholinergic neuron damage severely impacts spatial memory, suggesting both pathways are crucial for hippocampal function.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- The medial septum/vertical limb of the diagonal band of Broca (MSDB) is vital for hippocampal spatial memory.
- Both cholinergic and GABAergic MSDB neurons project to the hippocampus, and their damage impairs spatial memory.
Purpose of the Study:
- To investigate the specific roles of GABAergic and cholinergic MSDB neurons in spatial memory.
- To determine the effects of selective and combined lesions of these neuronal populations on memory performance.
Main Methods:
- Rats received intraseptal administration of kainic acid (to lesion GABAergic neurons), 192-IgG saporin (SAP; to lesion cholinergic neurons), or both.
- Spatial memory was assessed using the eight-arm radial maze and the water maze.
Main Results:
- Kainic acid selectively destroyed GABAergic MSDB neurons, while SAP eliminated cholinergic MSDB neurons.
- Selective lesions of either GABAergic or cholinergic neurons did not significantly impair radial maze performance.
- Combined lesions of both neuron types severely impaired performance in both the radial maze and water maze tasks.
Conclusions:
- GABAergic septohippocampal neurons are not essential for spatial memory acquisition or retention.
- Cholinergic MSDB neurons play a role in spatial memory, but their selective lesion causes only mild impairment.
- The combined damage to GABAergic and cholinergic MSDB neurons results in significant spatial memory deficits, indicating a synergistic role for both pathways.
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.
