瑞士苏黎世大学Fritjof Helmchen和Dominik Groos共同合作,近期取得重要工作进展。他们研究提出一个独特的下丘脑-缰核回路调控着风险选择偏好。相关研究成果2025年1月8日在线发表于《自然—神经科学》杂志上。
据介绍,适当的风险评估对于在复杂、不确定的环境中生存至关重要。面对在某些确定(安全)和不确定(有风险)选项之间做出选择,动物在很长一段时间内对这两种选项都表现出强烈的偏好。这种风险偏好在大脑中是如何编码的仍然难以捉摸。一个候选区域是外侧缰核(LHb),它在价值导向行为中起着重要作用。
研究人员使用平衡的双选择任务和小鼠的纵向双光子钙成像技术,确定了LHb神经元在行动选择之前,反映个体风险偏好的风险偏好选择性活动。通过使用全脑解剖追踪、多纤维光度测定,和投射特异性和细胞类型特异性光遗传学技术,研究人员发现来自内侧下丘脑(MH)而非外侧下丘脑(LH)的谷氨酸能LHb投射,会在行动选择之前提供与行为相关的突触输入。MH→LHb轴突的光致刺激诱发兴奋性和抑制性突触后反应,而LH→LHb投射是兴奋性的。
因此,研究人员揭示了在习惯性经济决策中,下丘脑 - 缰核回路对于风险偏好具有功能上不同的作用机制。
附:英文原文
Title: A distinct hypothalamus–habenula circuit governs risk preference
Author: Groos, Dominik, Reuss, Anna Maria, Rupprecht, Peter, Stachniak, Tevye, Lewis, Christopher, Han, Shuting, Roggenbach, Adrian, Sturman, Oliver, Sych, Yaroslav, Wieckhorst, Martin, Bohacek, Johannes, Karayannis, Theofanis, Aguzzi, Adriano, Helmchen, Fritjof
Issue&Volume: 2025-01-08
Abstract: Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive. A candidate region is the lateral habenula (LHb), which is prominently involved in value-guided behavior. Here, using a balanced two-alternative choice task and longitudinal two-photon calcium imaging in mice, we identify risk-preference-selective activity in LHb neurons reflecting individual risk preference before action selection. By using whole-brain anatomical tracing, multi-fiber photometry and projection-specific and cell-type-specific optogenetics, we find glutamatergic LHb projections from the medial (MH) but not lateral (LH) hypothalamus providing behavior-relevant synaptic input before action selection. Optogenetic stimulation of MH→LHb axons evoked excitatory and inhibitory postsynaptic responses, whereas LH→LHb projections were excitatory. We thus reveal functionally distinct hypothalamus–habenula circuits for risk preference in habitual economic decision-making.
DOI: 10.1038/s41593-024-01856-4
Source: https://www.nature.com/articles/s41593-024-01856-4
Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex