A morphogenetic role for acetylcholine in mouse cerebral neocortex.

Area of Science:

• Neuroscience
• Developmental Biology
• Cognitive Science

Background:

• Cholinergic afferents to the cerebral cortex are increasingly recognized for their roles in regulating neural plasticity and cognitive functions.
• Understanding the impact of early-life cholinergic signaling on cortical development is crucial for comprehending cognitive processes.

Purpose of the Study:

• To investigate the long-term consequences of neonatal cholinergic deafferentation on cortical development and cognitive behavior in mice.
• To explore the sex-dependent nature of these developmental alterations.

Main Methods:

• Development of a neonatal basal forebrain lesion paradigm in mice.
• Assessment of neuronal differentiation, synaptic connectivity, and cognitive behaviors in lesioned and control mice.
• Analysis of sex-specific morphological and molecular changes.

Main Results:

• Transient neonatal cholinergic deafferentation leads to persistent alterations in neuronal differentiation and synaptic connectivity.
• These alterations result in modified cognitive behaviors in mature mice.
• The morphological and behavioral consequences of the lesion are sex-dependent, with rapid molecular changes observed.

Conclusions:

• Early-life cholinergic signaling is critical for normal cortical development and cognitive function.
• Neonatal basal forebrain lesions induce lasting, sex-specific changes in the mouse brain.
• Sex-dependent molecular mechanisms likely underlie the observed developmental and behavioral outcomes.