Acetylcholine Neurons Become Cholinergic during Three Time Windows in the Developing Mouse Brain.

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Neurobiology

Background:

• Acetylcholine (ACh) neurons are vital for central nervous system functions like attention, learning, memory, and locomotion.
• Dysfunctional cholinergic signaling is implicated in neurodevelopmental and neurodegenerative disorders.
• The developmental timeline of cholinergic system maturation remains largely uncharacterized.

Purpose of the Study:

• To determine when acetylcholine (ACh) neurons acquire their cholinergic identity during brain development.
• To map the temporal emergence of cholinergic signaling in the developing brain.
• To understand the coordination between ACh neuron development and brain anatomical structure.

Main Methods:

• Utilized transgenic mice for selective labeling of acetylcholine (ACh) neurons using tdTomato.
• Performed whole-brain imaging of serially sectioned brains at various prenatal and postnatal developmental stages.
• Generated 3D whole-brain reconstructions to analyze developmental timing.

Main Results:

• Identified three critical developmental windows (two prenatal, one postnatal) for the acquisition of cholinergic identity in most ACh neuron populations.
• Demonstrated that cholinergic gene expression begins in cortical ACh interneurons.
• Showed that cholinergic projection neurons from the basal forebrain innervate the cerebral cortex.
• Established that ACh neuron populations become cholinergic before postnatal day 12, preceding the onset of major sensory processes.

Conclusions:

• Acetylcholine (ACh) neuron populations are established and become functional before the onset of major sensory development.
• The birth of ACh neurons and the initiation of cholinergic gene expression are distinct but coordinated developmental events.
• Brain anatomical structure plays a crucial role in coordinating the temporal development of the cholinergic system.