A prefrontal cortex-lateral hypothalamus circuit controls stress-driven increased food intake

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Neurobiology

Background:

• Stress is a known contributor to overconsumption of palatable foods, particularly high-fat options.
• The medial prefrontal cortex (mPFC) plays a role in stress-related eating behaviors, but the specific neural circuits involved are not fully understood.

Purpose of the Study:

• To elucidate the circuit mechanisms by which the medial prefrontal cortex (mPFC) influences stress-induced high-fat food intake.
• To investigate the role of mPFC projections to the lateral hypothalamus (LHA) in mediating stress-eating behaviors.

Main Methods:

• Utilized optogenetic stimulation and inhibition techniques in male mice to probe the function of the mPFC-LHA pathway.
• Employed circuit mapping techniques to identify specific neuronal populations within the LHA targeted by mPFC projections.
• Assessed changes in synaptic plasticity at mPFC-LHA synapses following social stress exposure.

Main Results:

• Activation of the mPFC-LHA pathway increased fat intake, even in sated states.
• Social stress acutely activated mPFC neurons projecting to the LHA.
• Inhibiting the mPFC-LHA pathway selectively blocked stress-induced overconsumption of high-fat foods.
• Stress induced plasticity at mPFC synapses onto LHA_VGLUT2 neurons, weakening inhibitory and strengthening excitatory connections related to feeding behavior.

Conclusions:

• The mPFC-LHA neural pathway is indispensable for stress-driven high-fat food intake in male mice.
• Specific plasticity changes within the mPFC-LHA_VGLUT2 circuit transform stress signals into heightened fat consumption.
• The mPFC-LHA represents a critical multi-branched network underlying stress-eating.