Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Resting-state functional MRI (rsfMRI) is crucial for studying brain topology in health and disease.
• Animal models, particularly mice, offer advantages for pharmacological and genetic brain modulation.
• Neurotransmitter systems like cholinergic and serotonergic are implicated in cognitive and emotional functions and neurological disorders.

Purpose of the Study:

• To investigate the effects of cholinergic and serotonergic antagonists on large-scale brain networks in mice.
• To examine the impact of these antagonists on the default-mode-network (DMN)-like network.
• To understand the role of specific neurotransmitter systems in functional network disruptions relevant to neurological disorders.

Main Methods:

• Utilized pharmacological manipulations targeting cholinergic and serotonergic systems in mice.
• Employed resting-state functional MRI (rsfMRI) to assess functional connectivity (FC) across brain networks.
• Analyzed alterations in network integrity, with a specific focus on the DMN-like network.

Main Results:

• Both cholinergic and serotonergic antagonists similarly impaired the mouse DMN-like network.
• Cholinergic modulation uniquely affected the retrosplenial cortex within the DMN-like network.
• Serotonergic modulation showed more extensive impairment in frontal and thalamus networks compared to cholinergic modulation.

Conclusions:

• Both cholinergic and serotonergic systems are vital for maintaining the integrity of the DMN-like network in mice.
• Pharmacological rsfMRI in animal models is a valuable tool for elucidating neurotransmitter roles in neurological conditions.
• Findings provide insights into how specific neurotransmitter dysfunctions may contribute to network disruptions in diseases like Alzheimer's, depression, and autism.