Effects of neonatal cholinergic basal forebrain lesions on excitatory amino acid receptors in neocortex

The role of cholinergic basal forebrain projections in the modulation of cortical plasticity and associated functional changes is currently the subject of renewed attention. Excitatory amino acid receptors have been identified as mediators of cortical topographic efferent and afferent information. In addition some of these receptors, notably the NMDA and metabotropic [mGluR] type, participate in cortical plasticity. Growing evidence suggests that interactions between cholinergic and glutamatergic systems contribute to cognitive cortical functions and their anatomical and physiological substrates. Though cholinergic and glutamatergic mechanisms have both been shown to be involved in cortical morphogenesis, few studies have attempted to study their interactions in development. The present study investigates the effect of neonatal lesions to the cholinergic basal forebrain on NMDA, AMPA and mGluR receptors in BALB/CByJ mice, at two different developmental ages. We demonstrated previously that nBM lesions at birth result in transient cholinergic depletion for the first two postnatal weeks, substantial morphogenetic alterations in neocortex and cognitive deficits by adulthood. We show here that unilateral neonatal lesions result in decreases in NMDA and AMPA receptors but increases in mGluRs during the second posnatal week (PND 14). At 30 days postnatal, lesion mediated changes were attenuated, compared with PND 14, but significant sex differences in control and nBM lesioned mice were apparent. These data support the notion that cholinergic/glutamatergic interactions are important during early cortical morphogenesis. Moreover, our results highlight the fact that cholinergic as well glutamatergic developmental mechanisms are sexually dimorphic.