Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood

Gregory John Sengstock, Kevin B. Johnson, Paul T. Jantzen, Edwin M. Meyer, Adrian J. Dunn, Gary W. Arendash

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Ibotenic acid was infused into the nucleus basalis magnocellularis (nBM) of 2-day old rats to eliminate immature cholinergic neurons before they develop functional synaptic connections in the neocortex. For bilaterally lesioned neonates, cognitive testing was initiated 2 months after lesioning and animals were sacrificed at 8 or 12 months of age. Lesioned animals exhibited a marked deficit in the retention of passive avoidance behavior, as well as in the acquisition of 2-way active avoidance behavior. Lesioned animals also made significantly more alternation errors than control animals in the Lashley III spatial maze and showed severe impairments in general learning, reference memory and working memory during 17-arm radial maze testing. For all 4 tasks, neonatally lesioned animals did not show any recovery to the performance level of control animals. Histological analysis of the subcortex from lesioned animals during adulthood revealed: (1) a substantial reduction in acetylcholinesterase-positive cells (presumably cholinergic) within the nucleus basalis, (2) decreased acetylcholinesterase staining in neocortex and (3) a gliosis essentially restricted to the globus pallidus. Surrounding brain regions were apparently not damaged as a direct result of excitotoxin infusion. Neurochemically, neonate nBM lesioning produced a long term cholinergic hypofunction as evidenced by significant reductions of 25% and 18% in frontal cortex chorine acetyltransferase (CAT) activity at 12 and 8 months of age, respectively. By contrast, prefrontal cortical concentrations of biogenic amines and their metabolites were unaffected, thus indicating a degree of neurochemical specificity for these neonatal nBM lesions. The persistant cortical cholinergic hypofunction in lesioned animals may be related to the long term deficits in learning/memory abilities that were also observed. It is suggested that neonatal nBM lesioning could provide a useful animal model for elucidating the plasticity of the developing brain after cortical anervation.

Original languageEnglish (US)
Pages (from-to)163-174
Number of pages12
JournalExperimental Brain Research
Volume90
Issue number1
DOIs
StatePublished - Jan 1 1992

Fingerprint

Cholinergic Agents
Basal Nucleus of Meynert
Avoidance Learning
Neocortex
Acetylcholinesterase
Learning
Ibotenic Acid
Acetyltransferases
Cholinergic Neurons
Globus Pallidus
Aptitude
Biogenic Amines
Gliosis
Neurotoxins
Brain
Frontal Lobe
Short-Term Memory
Animal Models
Staining and Labeling

Keywords

  • Acetylcholine
  • Cognition
  • Excitotoxic lesions
  • Neonate
  • Nucleus basalis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood. / Sengstock, Gregory John; Johnson, Kevin B.; Jantzen, Paul T.; Meyer, Edwin M.; Dunn, Adrian J.; Arendash, Gary W.

In: Experimental Brain Research, Vol. 90, No. 1, 01.01.1992, p. 163-174.

Research output: Contribution to journalArticle

Sengstock, Gregory John ; Johnson, Kevin B. ; Jantzen, Paul T. ; Meyer, Edwin M. ; Dunn, Adrian J. ; Arendash, Gary W. / Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood. In: Experimental Brain Research. 1992 ; Vol. 90, No. 1. pp. 163-174.
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