A decrease in size and number of basal forebrain cholinergic neurons is paralleled by diminished hippocampal cholinergic innervation in mice lacking leukocyte common antigen related protein tyrosine phosphatase activity

Citation
Emm. Van Lieshout et al., A decrease in size and number of basal forebrain cholinergic neurons is paralleled by diminished hippocampal cholinergic innervation in mice lacking leukocyte common antigen related protein tyrosine phosphatase activity, NEUROSCIENC, 102(4), 2001, pp. 833-841
Citations number
57
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
03064522 → ACNP
Volume
102
Issue
4
Year of publication
2001
Pages
833 - 841
Database
ISI
SICI code
0306-4522(2001)102:4<833:ADISAN>2.0.ZU;2-Q
Abstract
The leukocyte common antigen-related (LAR) receptor, composed of an extrace llular region with three immunoglobulin-like and eight fibronectin type III -like domains, and a cytoplasmic region containing two protein tyrosine pho sphatase domains, is thought to play a role in axonal outgrowth and guidanc e during neural development. LAR mutant mice were generated completely tack ing the two cytoplasmic protein tyrosine phosphatase domains, resulting in the loss of ability to bind intracellular associating proteins, but (may be ) still containing the ability to perform extracellular functions. A reduct ion in size of basal forebrain cholinergic neurons and diminished hippocamp al innervation reponed for knockout mice that contain a leaky gene trap ins erted into the 5' part of the LAR gene [Yeo T. T. et al. (1997) J. Neurusci . Res. 47, 348-360] warranted a computer-assisted quantitative image analys is throughout the basal forebrain and hippocampus of our LAR mutant mice. T he total number, longest diameter and cell body area were calculated for th e choline acetyltransferase-positive neurons in the medial septum and verti cal diagonal band, and optical density measurements were performed to deter mine the extent of acetyl cholinesterase-positive fibre innervation of the different layers in the dentate gyrus. In LAR mutant mice, the number of ch olinergic cells was significantly reduced (similar to 25%) in the vertical diagonal band. Also. the cross-sectional area of the cholinergic neurons in the medial septum and vertical diagonal band was reduced (5%). These findi ngs were paralleled by a diminished cholinergic innervation of the supragra nular (18%) and molecular (4%) layers of the dentate gyrus. Thus, LAR protein tyrosine phosphatase activity appears crucial for size, n umber and target projection of basal forebrain cholinergic neurons, further strengthening a role for LAR in CNS development. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.