Dissociable effects on spatial maze and passive avoidance acquisition and retention following AMPA- and ibotenic acid-induced excitotoxic lesions of the basal forebrain in rats: Differential dependence on cholinergic neuronal loss

Page, K. J., Everitt, B. J., Robbins, T. W., Marston, H. M. and Wilkinson, Lawrence Stephen ORCID: https://orcid.org/0000-0002-9337-6124 1991. Dissociable effects on spatial maze and passive avoidance acquisition and retention following AMPA- and ibotenic acid-induced excitotoxic lesions of the basal forebrain in rats: Differential dependence on cholinergic neuronal loss. Neuroscience 43 (2-3) , pp. 457-472. 10.1016/0306-4522(91)90308-B

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Abstract

Excitotoxic lesions of the basal forebrain were made by infusing either α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or ibotenic acid. Acquisition and performance of spatial learning in the Morris water maze, over a ten day, two trials per day, training regimen were unaffected by the AMPA-induced lesions which reduced cortical choline acetyltransferase activity by 70%. However, acquisition was significantly impaired in rats with ibotenic acid-induced lesions that reduced cortical choline acetyltransferase by 50%. Additionally, ibotenic acid-lesioned rats swam further than either sham or AMPA-lesioned rats, in the “training” quadrant during a probe trial, in which the escape platform was removed, suggesting a perseverative search strategy. Lesions induced with AMPA, but not ibotenate, significantly impaired the acquisition of “step-through” passive avoidance. Both AMPA- and ibotenateinduced lesions significantly impaired the 96 h retention of passive avoidance, but the effect of AMPA was greater on latency measures. Histological analysis revealed that AMPA infusions destroyed more choline acetyltransferase-immunoreactive neurons than did ibotenate infusions but, unlike ibotenate, spared the overlying dorsal palhdum and also parvocellular, non-choline acetyltransferase-immunoreactive neurons in the ventral pallidal/substantia innominata region of the basal forebrain. The impairment in acquisition of the water maze following ibotenate-induced basal forebrain lesions therefore appears unrelated to damage to cholinergic neurons of the nucleus basalis of Meynert and to depend instead on damage to pallidal and other neurons in this area. The AMPA- and perhaps also the ibotenate-induced impairment in the retention of passive avoidance appears to be more directly related to destruction of cholinergic neurons of the nucleus basalis. These data are discussed in the context of cortical cholinergic involvement in mnemonic processes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI) Psychology
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	AChE acetylcholinesterase; AMPA α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; BF basal forebrain; BNST bed nucleus of the stria terminalis; ChAT choline acetyltransferase; DAB diaminobenzidine; EL escape latency; -IR immunoreactivity; nbM nucleus basalis of Meynert; NMDA N-methyl-d-aspartate; PA passive avoidance; PAP peroxidaseantiperoxidase; PB phosphate buffer; PBS phosphatebuffered saline
Publisher:	Elsevier
ISSN:	0306-4522
Last Modified:	31 Oct 2022 10:36
URI:	https://orca.cardiff.ac.uk/id/eprint/85447

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