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Published on: February 26, 2018
State-dependent neurotensin modulation in the brain: From network dynamics to pharmacological opportunity
Shengru Hu1, Zixu Zhang1, Wei Xie2
1School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, PR China; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, PR China.
Abstract:
Neurotensin (NT) is a conserved neuropeptide acting as a critical state-dependent neuromodulator across hypothalamic, limbic, and brainstem circuits. Historically categorized by discrete behavioral effects, recent spatial transcriptomic and functional breakthroughs reveal a unifying computational logic: NT signaling modulates how neural circuits integrate and prioritize competing motivational and homeostatic signals. Crucially, NT-dependent effects emerge predominantly under physiological challenge, uncertainty, or conflicting demands, biasing the probability of behavioral outputs through conditional gain-control. This framework reconciles divergent findings and highlights NT receptors (NTSR1/NTSR2) as highly tractable pharmacological targets. The development of subtype-selective and biased agonists offers novel therapeutic avenues for modulating adaptive behavior in psychiatric, metabolic, and pain-related disorders.
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