Striosomal ghrelin receptor activity controls reward-cost integration

Area of Science:

• Neuroscience
• Endocrinology
• Decision-making research

Background:

• Growth hormone secretagogue receptors (GHSRs) are known to affect reward and cost processing.
• The specific role of GHSRs in complex decision-making, particularly under conflict, remains largely unexplored.

Purpose of the Study:

• To investigate the effects of GHSR activation on conflict-based decision-making in a rat model.
• To elucidate the neural circuits underlying GHSR modulation of decision-making processes.

Main Methods:

• Administered varying doses of the GHSR agonist ibutamoren (IBU) to rats and assessed decision-making performance.
• Examined GHSR expression in brain regions relevant to decision-making, including the dorsomedial striosomes.
• Utilized neuronal activity recordings and chemogenetic manipulations to investigate circuit mechanisms.

Main Results:

• Moderate doses of IBU selectively increased cost sensitivity in conflict paradigms, showing a dose-dependent effect.
• GHSR activation modulated neuronal activity in dorsomedial striosomes, projecting to the lateral habenula (LHb) and substantia nigra pars compacta (daSNc).
• Chemogenetic manipulation confirmed the causal role of dorsomedial striosomes in GHSR-mediated effects on cost sensitivity and circuit activity.

Conclusions:

• GHSRs play a critical role in modulating cost sensitivity during conflict-based decision-making.
• A novel circuit involving dorsomedial striosomes, LHb, and daSNc mediates the effects of endocrine activity on decision-making.
• This study identifies a new link between endocrine signals and the neural mechanisms governing complex choices.