Upper brainstem cholinergic neurons project to ascending and descending circuits

Area of Science:

• Neuroscience
• Cell Biology
• Neuroanatomy

Background:

• Ascending and descending circuits are defined by rostral and caudal projections, respectively.
• Upper brainstem neurons are crucial for complex information processing.
• Cholinergic neurons in the upper brainstem have widespread projections, but individual neuron pathways are not well understood.

Purpose of the Study:

• To comprehensively characterize the single-cell projection patterns of pontine-tegmental cholinergic neurons (PTCNs).
• To elucidate the role of PTCNs in ascending and descending brain circuits.
• To classify PTCN subtypes based on their axonal morphology and connectivity.

Main Methods:

• Utilized fluorescent micro-optical sectional tomography combined with sparse labeling for high-resolution whole-brain imaging.
• Employed semi-automatic reconstruction methods to detail the morphology of individual PTCNs.
• Analyzed axonal collateralization within ascending and descending circuits.

Main Results:

• Individual PTCNs possess extensive axons (up to 60 cm) with numerous terminals (up to 5000), innervating widespread brain regions bilaterally.
• Four distinct PTCN subtypes were identified based on their collateralization patterns in ascending and descending circuits.
• PTCNs demonstrated varied innervation patterns to the thalamus and cortex, with specific projections to the ventral tegmental area and substantia nigra influencing locomotion via pontine reticular nuclei.

Conclusions:

• Individual PTCNs exhibit extensive axonal branching, simultaneously projecting to multiple collaterals within both ascending and descending circuits.
• PTCNs target various brain regions, including the thalamus and cortex, through diverse innervation patterns.
• This detailed characterization of PTCNs provides a foundational understanding of upper brainstem connexional logic.