MetaTOC stay on top of your field, easily

Integration of cortical inputs in the lateral hypothalamus is dominated by the medial prefrontal cortex

, , ,

The Journal of Physiology

Published online on

Abstract

["The Journal of Physiology, EarlyView. ", "\nAbstract figure legend The lateral hypothalamus (LH) is a critical controller of innate behaviours such as feeding. It is anatomically connected to specific cortical areas. We mapped these areas using a combination of retrograde tracing and anterograde optogenetic circuit mapping. The medial prefrontal and insular cortices are key sources of neocortical output, and they have different synaptic dynamics. Dual‐colour optogenetics revealed that these inputs are integrated supralinearly and are routed to partially distinct LH cells depending on their intrinsic electrophysiological properties. Cortical input from specific associative areas is integrated within individual LH neurons and affects their action potential output. \n\n\n\n\n\n\n\n\n\nAbstract\nThe lateral hypothalamus (LH) is a critical brain region orchestrating survival behaviours, including feeding. Its sparse local synaptic connectivity allows long‐range projections to modulate its activity. Some of these projections arise from the cerebral cortex, which is known to influence feeding. However the functional and anatomical organization of cortico‐hypothalamic pathways has remained poorly studied. We used anatomical and optogenetic mapping to show that the medial prefrontal cortex (mPFC) is the strongest cortical input source to the LH, followed by a lateral associative region, including the insular cortex (IC), and the ventral subiculum. Inputs from the mPFC and IC had markedly different synaptic dynamics and were integrated supralinearly. IC input surpassed that of the mPFC in a subpopulation of highly excitable dorsal LH neurons which had a strong h‐current. Input from the mPFC showed selective targeting to LH neurons which project back to the mPFC, suggesting the existence of a direct feedback loop. Overall these results identify a direct prefrontal–hypothalamic pathway which is poised to dominate rapid cortical control of hypothalamic activity.\n\n\n\n\n\n\n\n\n\nKey points\n\nThe lateral hypothalamus (LH) receives monosynaptic, excitatory cortical synaptic input from associative cortical regions and hippocampus.\nCortical input is integrated temporally in a pathway‐specific manner within individual LH neurons.\nInputs from the medial prefrontal cortex (mPFC) and insula are integrated supralinearly.\nThe mPFC is a dominant source targeting LH neurons projecting back to the mPFC.\n\n\n"]