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Do GAT1-saporin lesions of the medial septum damage GABAergic afferents to the medial septum?

Gielow M, Roland J, Servatius, RJ Pang KCH (2010) Do GAT1-saporin lesions of the medial septum damage GABAergic afferents to the medial septum?. Neuroscience 2010 Abstracts 811.3/LLL66. Society for Neuroscience, San Diego, CA.

Summary: 192-IgG saporin is an antibody directed to the p75 receptor conjugated to the ribosomal-inactivating compound saporin. 192-IgG saporin has been widely used to selectively ablate cholinergic cells of the basal forebrain. Cholinergic lesions are typically made by injections of 192-IgG saporin at the soma in basal forebrain nuclei. However, 192-IgG saporin is also effective in damaging specific cholinergic projections by administration of the toxin in the axon terminal region. Recently, GAT1-saporin has been developed as a tool to selectively damage cells expressing the GABA transporter GAT1. GAT1-saporin combines an antibody to the GABA transporter GAT1 with saporin. GAT1 transporters are primarily localized to neurons and GAT1-saporin has been shown to selectively damage GABAergic neurons in the BNST and medial septum. Given the similarity to 192-IgG saporin, a major question is whether GAT1-saporin is effective in damaging GABAergic afferents to the area of administration. Our previous studies found that GAT1-saporin administered to the medial septum / diagonal band of Broca (MSDB) damages GABAergic septohippocampal neurons and impaired performance on delayed match to position tasks. While it seems likely that damage of GABAergic MSDB neurons is responsible for these behavioral impairments, one cannot rule out the possibility that destruction of GABAergic afferents to the MSDB may also contribute. Therefore, the present study was undertaken to determine whether GAT1-saporin lesions of the MSDB damage the GABAergic hippocamposeptal projection. Male Sprague Dawley rats received both fluorogold and either GAT1-saporin or vehicle in medial septum. Immunocytochemistry for choline acetyltransferase and parvalbumin confirmed the extent of the lesion. The majority of hippocamposeptal GABAergic neurons contain the neuropeptide somatostatin. Quantification of double-labeled hippocampal fluorogold-positive cell bodies with anti-somatostatin immunofluorescence was performed using unbiased stereology. Preliminary data suggest that GABAergic hippocamposeptal neurons are intact. These results will be important in understanding the damage produced by GAT1-saporin.

Related Products: GAT1-SAP (Cat. #IT-32)