Koutlas Ioannis, Patrikiou Lefkothea, van der Starre Stef E, Danko Diaz, Wolterink-Donselaar Inge G, Luijendijk Mieneke C M, Adan Roger A H, Meye Frank J
Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht University, Utrecht, the Netherlands.
Nat Commun. 2025 Apr 2;16(1):3147. doi: 10.1038/s41467-025-58384-3.
Assigning valence to stimuli for adaptive behavior is an essential function, involving the ventral tegmental area (VTA). VTA cell types are often defined through neurotransmitters (NT). However, valence function in VTA does not parse along NT-boundaries as, within each NT-class, certain neurons are excited by reward and others by stressors. Here we identify, in male mice, the co-activated VTA neuronal ensembles for reward and stress, and determine their role in adaptive behaviors. We show that stimuli of opposite valence (opioid vs acute social stress) recruit two distinct VTA neuronal ensembles. These two ensembles continue to be preferentially engaged by congruent valence stimuli. Stimulation of VTA stress- or reward ensembles is aversive/reinforcing, respectively. Strikingly, external valence stimuli fully require activity of these small discrete VTA ensembles for conferring approach/avoidance outcomes. Overall, our study identifies distinct VTA ensembles for positive and negative valence coding and shows their indispensability for adaptive behavior.
为适应性行为的刺激赋予效价是一项基本功能，涉及腹侧被盖区（VTA）。VTA细胞类型通常通过神经递质（NT）来定义。然而，VTA中的效价功能并不按照NT界限进行划分，因为在每个NT类别中，某些神经元被奖励激活，而其他神经元则被应激源激活。在这里，我们在雄性小鼠中识别出用于奖励和应激的共同激活的VTA神经元集群，并确定它们在适应性行为中的作用。我们表明，具有相反效价的刺激（阿片类药物与急性社会应激）会招募两个不同的VTA神经元集群。这两个集群继续被具有相同效价的刺激优先激活。刺激VTA应激或奖励集群分别具有厌恶/强化作用。引人注目的是，外部效价刺激完全需要这些小的离散VTA集群的活动来赋予接近/回避结果。总体而言，我们的研究确定了用于正性和负性效价编码的不同VTA集群，并表明它们对于适应性行为不可或缺。
