Neurotensin-specific corticothalamic circuit regulates innate response conflict

Curr Biol. 2024 Aug 5;34(15):3473-3487.e6. doi: 10.1016/j.cub.2024.06.068. Epub 2024 Jul 26.

Abstract

Animals must simultaneously select and balance multiple action contingencies in ambiguous situations: for instance, evading danger during feeding. This has rarely been examined in the context of information selection; despite corticothalamic pathways that mediate sensory attention being relatively well characterized, neural mechanisms filtering conflicting actions remain unclear. Here, we develop a new loom/feed test to observe conflict between naturally induced fear and feeding and identify a novel anterior cingulate cortex (ACC) output to the ventral anterior and ventral lateral thalamus (VA/VL) that adjusts selectivity between these innate actions. Using micro-endoscopy and fiber photometry, we reveal that activity in corticofugal outputs was lowered during unbalanced/singularly occupied periods, as were the resulting decreased thalamic initiation-related signals for less-favored actions, suggesting that the integration of ACC-thalamic firing may directly regulate the output of behavior choices. Accordingly, the optoinhibition of ACC-VA/VL circuits induced high bias toward feeding at the expense of defense. To identify upstream "commander" cortical cells gating this output, we established dual-order tracing (DOT)-translating ribosome affinity purification (TRAP)-a scheme to label upstream neurons with transcriptome analysis-and found a novel population of neurotensin-positive interneurons (ACCNts). The photoexcitation of ACCNts cells indeed caused similarly hyper-selective behaviors. Collectively, this new "corticofugal action filter" scheme suggests that communication in multi-step cingulate circuits may critically influence the summation of motor signals in thalamic outputs, regulating bias between innate action types.

Keywords: anterior cingulate cortex; behavior bias; corticothalamic circuit; innate response conflict; neurotensin.

MeSH terms

  • Animals
  • Fear / physiology
  • Feeding Behavior
  • Gyrus Cinguli* / metabolism
  • Gyrus Cinguli* / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways* / physiology
  • Neurotensin* / metabolism
  • Thalamus / metabolism
  • Thalamus / physiology

Substances

  • Neurotensin