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

Abstract

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 postnatal 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.

Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats

“…Thus, lesions of the basal forebrain cholinergic system in neonatal mice (PN 0) cause a decrease in AMPA and NMDA receptors in the neocortex during the PN 14. 13 It is therefore possible that an abnormal development of the cholinergic system, induced by prenatal choline deficiency in the present study, had disrupted the cholinergic-glutamatergic interaction and consequently had caused a deficit in the retention of the familiar object.…”

Sleep-Wake Sensitive Mechanisms of Adenosine Release in the Basal Forebrain of Rodents: An In Vitro Study

“…Metabotropic glutamate receptors (mGluRs) have also been reported present in BFB neurons and glia [44]–[46], and so mGluRs were also tested to see whether they evoked adenosine release. The group I mGluR agonist (1S,3R) ACPD at 50–100 µM reliably evoked adenosine release, although this was not reliably accompanied by neuronal depolarization (figures 1e,f).…”

Morphological Effects of Estrogen on Cholinergic NeuronsIn VitroInvolves Activation of Extracellular Signal-Regulated Kinases

“…Of direct relevance to our study, the ventral paleostriatum, the origin of the cholinergic innervation of the song control nuclei in the zebra finch, contains cholinergic neurons that are of bigger size and higher density in males than in females (Sakaguchi et al, 2000). In mice, basal forebrain lesions at birth result in sex-specific changes in binding to cortical glutamatergic receptors (Hohmann et al, 1998). It is also known that endocrine regulation of sexually dimorphic brain structures is genetically controlled (Lephart et al, 2001), particularly by E 2 .…”