Hypothalamic Circuits For Predation And Evasion

The interactions between predator and prey represent some of the most dramatic events in nature,and constitute a matter of life-and-death for both sides.The hypothalamus has been implicated in driving predation and evasion;however,the exact hypothalamic neural circuits underlying these behaviors remain poorly defined.Here,we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus(LH)to the periaqueductal gray(PAG)in the midbrain drive,respectively,predation and evasion.Using a dual-virus strategy,we found an increase in the activity of PAG-projecting LH neurons starting when starving mice began to hunt crickets.Activating these PAG-projecting LH neurons drove predatory attack.In patch-clamp recordings of brain slices,stimulating the axonal terminals from retrograde-labeled LH neurons evoked a mixture of GABAergic inhibitory currents and glutamatergic excitatory currents in PAG neurons,indicating that these PAG-projecting LH neurons can release the neurotransmitters GABA and/or glutamate.LH GABA neurons were activated during predation.Inhibition of LH GABA neurons suppressed cricket-hunting behavior.In a computer controled food-chasing task,optogenetic inhibition of LH GABA neurons during the initiation stage prevented mice from chasing the moving food dish.However,inhibition applied immediately after pellet retrieval did not disrupt an animal's gnawing(putatively consummatory)behavior.Cell type-specifc activation of LH GABA neurons drove predatory attack upon cricket,an artifitial prey and intraspecifc targets.Both cell type-specifc and projection-specifc stimulating of PAG-projecting LH GABA neurons drove strong predatory attack,and inhibiting of these cells reversibly blocked predation.In contrast,LH glutamate neurons were activated during evasion.Stimulating PAGprojecting LH glutamate neurons drove evasion,and inhibiting them impeded predictive evasion.Therefore,the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG.