Neonatal basal forebrain lesions alter excitatory amino acid receptor development in cortex

Previously, our lab developed a mouse model in which neonatal lesions in the area of the basal forebrain cholinergic projection neurons [nBM] lead to altered maturation and subsequent impaired function of cortex. We have shown that neonatal [nBM] lesions result in transient cholinergic and to a lesser degree monoaminergic depletion of the developing cortex. Subsequent morphogenetic abnormalities include altered dendritic morphogenesis of neocortical pyramidal neurons and permanent changes in cortical layer width. Behavioral alterations include retention deficits on a passive avoidance task and acquisition deficits in the Morris water maze. Since NMDA and other excitatory amino acid receptors have been shown widely to influence cortical plasticity as well as memory and learning, the present study seeks to assess whether neonatal [nBM] lesions alter ligand binding to EAA receptors. We have investigated the effect of neonatal [nBM] lesions on the NMDA, AMPA and metabotrophic glutamate receptors in cortex using receptor binding audio radiography followed by computerized quantification. Current data show that NMDA receptors are significantly decreased ipsilateral to the nBM at postnatal day 14 and 30. Metabotrophic, AMPA and Kainate receptors did not show significant changes at any of the ages investigated. The observed receptor change suggests that altered NMDA receptor expression may be involved in both the morphological and behavioral alterations seen after neonatl nBM lesions. Moreover, NMDA receptor changes similar to those seen in our mouse model may also contribute to mental retardation syndromes such as Rett syndrome.