Moss Elizabeth H, Tantry Evelyne K, Le Elaine, Chin Pey-Shyuan, Ambrosi Priscilla, Brandel-Ankrapp Katie L, Arenkiel Benjamin R
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 97030
Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, Oregon 97239.
J Neurosci. 2025 Mar 26;45(13):e0200242025. doi: 10.1523/JNEUROSCI.0200-24.2025.
Sensory perception relies on the flexible detection and interpretation of stimuli across variable contexts, conditions, and behavioral states. The basal forebrain (BF) is a hub for behavioral state regulation, supplying dense cholinergic and GABAergic projections to various brain regions involved in sensory processing. Of GABAergic neurons in the BF, parvalbumin (PV) and somatostatin (SST) subtypes serve opposing roles toward regulating behavioral states. To elucidate the role of BF circuits in sensory-guided behavior, we investigated GABAergic signaling dynamics during odor-guided decision-making in male and female mice. We used fiber photometry to record cell type-specific BF activity during an odor discrimination task and correlated temporal patterns of PV and SST neuronal activity with olfactory task performance. We found that while both PV-expressing and SST-expressing GABAergic neurons were excited during trial initiation, PV neurons were selectively suppressed by reward, whereas SST neurons were excited. Notably, chemogenetic inhibition of BF SST neurons modestly altered decision bias to favor reward seeking, while optogenetic inhibition of BF PV neurons during odor presentations improved discrimination accuracy. Together, these results suggest that the bidirectional activity of GABAergic BF neuron subtypes distinctly influence perception and decision-making during olfactory-guided behavior.
感觉知觉依赖于在各种不同的环境、条件和行为状态下对刺激的灵活检测和解读。基底前脑(BF)是行为状态调节的枢纽,向参与感觉处理的各个脑区提供密集的胆碱能和γ-氨基丁酸能投射。在BF的γ-氨基丁酸能神经元中,小白蛋白(PV)和生长抑素(SST)亚型在调节行为状态方面发挥着相反的作用。为了阐明BF回路在感觉引导行为中的作用,我们研究了雄性和雌性小鼠在气味引导决策过程中的γ-氨基丁酸能信号动态。我们使用光纤光度法在气味辨别任务期间记录细胞类型特异性的BF活动,并将PV和SST神经元活动的时间模式与嗅觉任务表现相关联。我们发现,虽然在试验开始时,表达PV和表达SST的γ-氨基丁酸能神经元均被激活,但PV神经元会被奖励选择性抑制,而SST神经元则被激活。值得注意的是,化学遗传学抑制BF的SST神经元适度改变了决策偏向,使其更倾向于寻求奖励,而在气味呈现期间光遗传学抑制BF的PV神经元则提高了辨别准确性。总之,这些结果表明,BF的γ-氨基丁酸能神经元亚型的双向活动在嗅觉引导行为期间对感知和决策有明显影响。