AgRP neurons control structure and function of the medial prefrontal cortex

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Neuroendocrinology

Background:

• Hypothalamic AgRP neurons regulate feeding and non-feeding behaviors across development.
• These neurons are implicated in modulating various brain functions, but their precise role in higher-order cognitive processes remains unclear.

Purpose of the Study:

• To investigate the role of AgRP neurons in the development and function of the medial prefrontal cortex (mPFC).
• To explore the neural pathways through which AgRP neurons exert their influence on brain function.

Main Methods:

• Constitutive impairment and peripubertal chemogenetic inhibition of AgRP neurons in mice.
• Assessment of neuronal number and function in the mPFC.
• Analysis of oscillatory network activity, sensorimotor gating, and ambulatory behavior.
• Pharmacological intervention with clozapine and tracing of neural pathways.

Main Results:

• Impairment of AgRP neurons led to a numerical and functional reduction of mPFC neurons.
• Observed alterations in mPFC network activity, impaired sensorimotor gating, and modified ambulatory behavior.
• These behavioral and neural changes were reversible with clozapine administration and involved dopaminergic and thalamic pathways.

Conclusions:

• Hypothalamic AgRP neurons play a critical, previously unrecognized role in the development and adult function of mPFC circuits.
• AgRP neuron influence on higher-order brain functions is mediated via projections through the ventral tegmental area and medial thalamus.
• These findings reveal a novel link between energy balance regulation and complex cognitive processes controlled by the mPFC.