Bile Acids Regulate Accumbal Cholinergic Circuitry and Dopamine Release through TGR5 Activation

Area of Science:

• Neuroscience
• Gastroenterology
• Pharmacology

Background:

• High-calorie foods and alcohol have strong reinforcing effects mediated by mesolimbic circuits.
• Bile acid secretion is crucial for caloric intake, but its role in mesolimbic circuitry is unexplored.
• Bile acids may act as a common regulator for the mesolimbic effects of alcohol and fatty foods.

Purpose of the Study:

• To investigate the direct effects of bile acids on mesolimbic neural activity.
• To assess how bile acids modulate cholinergic interneuron firing and dopamine transmission in the nucleus accumbens.

Main Methods:

• Electrophysiological recordings from acute mouse brain slices.
• Assessment of bile acid effects on accumbal cholinergic interneuron firing and postsynaptic activity.
• Voltammetry to measure dopamine release and clearance in the nucleus accumbens.

Main Results:

• Low bile acid concentrations increased cholinergic interneuron firing via TGR5 activation and suppressed inhibitory currents.
• High bile acid concentrations decreased cholinergic interneuron firing and robustly inhibited dopamine release.
• Bile acids modulated inhibitory input frequency and amplitude in a concentration-dependent manner.

Conclusions:

• Bile acids directly modulate neural activity within the striatum.
• These findings highlight a novel role for bile acids in regulating brain reward pathways.