Orthogonal neural geometry of orientation, spatial frequency, and ocular dominance in macaque V1

猕猴初级视觉皮层（V1）中朝向、空间频率和眼优势的正交神经几何结构

The classical ice-cube model of Hubel and Wiesel proposes that V1 neurons are spatially organized into orthogonal maps of orientation and ocular dominance to optimize wiring efficiency. However, extending this framework to include additional features such as spatial frequency imposes constraints on how these features can be spatially arranged on the cortical surface. A recent two-photon imaging study of ours found that cellular-resolution maps of orientation, spatial frequency, and ocular dominance in macaque V1 lack consistent orthogonal or parallel spatial arrangements. To investigate whether these features are instead represented in population activity space, we applied principal component analysis (PCA) to these and additional datasets. We found that population responses formed near-orthogonal geometries in representational space, supporting the idea that feature encoding relies more on population-level activity than spatial layout. This orthogonal structure remained robust to dimensionality changes and was absent in response-shuffled control data, in which feature axes collapsed to chance-level alignment. Furthermore, artificially disrupting orthogonality, either by aligning feature axes or randomizing trial positions in PCA space, severely impaired the decodability of stimulus features, demonstrating that orthogonal representations are critical for maintaining feature separability. These findings suggest that V1 population responses follow an orthogonal encoding geometry, and that population codes, rather than spatial maps, better capture feature representation. This principle may also serve as an important benchmark for V1-inspired deep neural networks.

休伯尔和维泽尔提出的经典“冰块”模型认为，初级视觉皮层（V1）神经元在空间上被组织成方向和眼优势的正交图谱，以优化神经连接效率。然而，若将该框架扩展到包含空间频率等其他特征，就会对这些特征在皮层表面的空间排列方式产生限制。我们近期的一项双光子成像研究发现，猕猴V1中方向、空间频率和眼优势的细胞分辨率图谱并不存在一致的正交或平行空间排列。为了探究这些特征是否在群体活动空间中得到表征，我们对这些数据集以及其他额外数据集进行了主成分分析（PCA）。我们发现，群体反应在表征空间中形成了近乎正交的几何结构，这支持了特征编码更多依赖于群体水平活动而非空间布局的观点。这种正交结构在维度变化时保持稳健，而在打乱反应顺序的对照数据中则不存在，在对照数据里，特征轴的排列退化为随机水平。此外，通过对齐特征轴或随机化主成分分析空间中的试验位置来人为破坏正交性，会严重损害刺激特征的可解码性，这表明正交表征对于维持特征可分离性至关重要。这些发现表明，V1的群体反应遵循正交编码几何结构，并且群体编码而非空间图谱能更好地捕捉特征表征。这一原则也可能成为受V1启发的深度神经网络的重要基准。

REF: Wang X, Zhang SH, Tang SM, Yu C. Orthogonal neural geometry of orientation, spatial frequency, and ocular dominance in macaque V1. Prog Neurobiol. 2026;258:102874. doi:10.1016/j.pneurobio.2025.102874 PMID: 41478519

Sustained inhibitory dysfunction in complement component C1qa-deficient mice underlies epilepsy and comorbidities

补体成分C1qa缺陷小鼠的持续性抑制功能障碍是癫痫及其共病的基础

Neuronal networks undergo critical refinement throughout development and adulthood to maintain proper brain function. Dysregulation of complement component C1qa-including both up- and downregulation-has been linked to circuit dysfunction and neurological disorders such as epilepsy, primarily through effects on excitatory synapses. However, the impact of C1qa downregulation on inhibitory circuits remains poorly understood. We show that germline deletion of C1qa disrupts layer 6 somatostatin (SST)-expressing interneurons in the somatosensory cortex, which we propose underlies enhanced excitatory synaptic transmission, electrographic spike-and-wave discharges, anxiety-like behavior, and impaired sensory-driven behavior. Transplantation of medial ganglionic eminence (MGE)-derived interneuron precursors rescued behavioral deficits but did not abolish the seizure phenotype, underscoring the critical role of C1qa in maintaining inhibitory network integrity-while also suggesting that additional mechanisms beyond interneuron dysfunction contribute to the pathophysiology of absence seizures.

在整个发育过程和成年期，神经网络会经历关键的优化过程，以维持大脑的正常功能。补体成分C1qa的失调（包括上调和下调）主要通过对兴奋性突触的影响，与回路功能障碍和神经系统疾病（如癫痫）相关联。然而，C1qa下调对抑制性回路的影响仍知之甚少。我们发现，C1qa的种系缺失会破坏躯体感觉皮质中表达生长抑素（SST）的6层中间神经元，我们认为这是导致兴奋性突触传递增强、脑电图尖波 - 慢波放电、焦虑样行为以及感觉驱动行为受损的基础。移植内侧神经节隆起（MGE）来源的中间神经元前体细胞可挽救行为缺陷，但不能消除癫痫发作表型，这凸显了C1qa在维持抑制性网络完整性方面的关键作用，同时也表明除中间神经元功能障碍之外的其他机制也参与了失神发作的病理生理过程。

REF: Righes Marafiga J, Vu T, Bowlus J, Baraban SC. Sustained inhibitory dysfunction in complement component C1qa-deficient mice underlies epilepsy and comorbidities. Prog Neurobiol. 2026;258:102881. doi:10.1016/j.pneurobio.2026.102881 PMID: 41544964

Mixed-selective organization of reach and grasp in the primate fronto-parietal network

灵长类动物额顶网络中伸手和抓握的混合选择性组织

Reaching and grasping in primates require coordinated control of several parameters, such as grip type, wrist orientation, spatial position, and hand laterality. The anterior intraparietal (AIP) and rostral ventral premotor (F5) areas are key hubs in this process. This study used electrophysiological data to investigate how these parameters are co-represented in AIP and F5. The results indicate that neurons predominantly show mixed selectivity with stable temporal organization related to movement and pre-movement phases. This uncategorizable mixture of selectivity allows flexible decoding. Despite condition-dependent shifts, selectivity preferences were largely preserved across task conditions. Notably, object-related factors (orientation and position) remained more stable during grip type changes in AIP, whereas grip type was more stable in F5, suggesting a functional hierarchical organization of context-dependent coding in both areas. Together, despite the continuous range of mixed selectivity at the single-neuron level, neural ensembles exhibit a stable organization on the temporal and functional scales, enabling flexible readouts.

灵长类动物的伸手和抓握动作需要对多种参数进行协调控制，如抓握类型、手腕方向、空间位置和用手偏好。顶内前区（AIP）和吻侧腹侧运动前区（F5）是这一过程中的关键枢纽。本研究利用电生理数据来探究这些参数在AIP和F5中是如何共同表征的。结果表明，神经元主要表现出混合选择性，且具有与运动和运动前阶段相关的稳定时间组织。这种难以归类的选择性混合使得灵活解码成为可能。尽管存在条件依赖性的变化，但选择性偏好很大程度上在不同任务条件下得以保留。值得注意的是，在AIP中，与物体相关的因素（方向和位置）在抓握类型改变时保持相对稳定，而在F5中抓握类型更为稳定，这表明两个区域存在基于情境编码的功能性层级组织。总之，尽管单个神经元层面存在连续的混合选择性，但神经集合在时间和功能尺度上呈现出稳定的组织，从而实现灵活的信息读取。

REF: Fathian A, Lehmann SJ, Michaels JA, Scherberger H. Mixed-selective organization of reach and grasp in the primate fronto-parietal network. Prog Neurobiol. 2026;258:102889. doi:10.1016/j.pneurobio.2026.102889 PMID: 41620070

Prefrontal cortex interneurons and their contributions to attention, working memory, and adaptive behavior

前额叶皮质中间神经元及其对注意力、工作记忆和适应性行为的作用

Inhibitory interneurons play central roles in regulating the input and output of cortical circuits, which in prefrontal cortices (PFC) subserve attention control, working memory and adaptive behavior. Understanding how interneurons support these higher order cognitive functions is a key question in a growing number of studies. Here, we delineate recent progress by surveying molecular, functional and computational motifs of interneurons in the prefrontal cortex of nonhuman primates and rodents. Among multiple transcriptomic and molecular subtypes of neurons several electrophysiologically identified 'eType' interneurons are recruited during attention, learning, and working memory tasks. In nonhuman primate PFC, eType neurons with an inhibitory effect on the local circuit encode behaviorally relevant cues, unexpected outcomes, and tune working memory representations. These response profiles are consistent with the functional specializations proposed for PV+ , SST+ and VIP+ interneurons in rodents, which are recruited during attention and memory-guided tasks. We survey how these functional studies of interneuron types are supported by newly developed molecular and analytical tools and guided by computational studies that suggest unique circuit motifs for distinct types of interneurons to flexibly route synaptic inputs, compute prediction errors, and facilitate information retention in working memory.

抑制性中间神经元在调节皮质回路的输入和输出中起着核心作用，前额叶皮质（PFC）中的皮质回路支持注意力控制、工作记忆和适应性行为。了解中间神经元如何支持这些高阶认知功能是越来越多研究中的关键问题。在此，我们通过概述非人类灵长类动物和啮齿动物前额叶皮质中中间神经元的分子、功能和计算模式来描述近期进展。在多种转录组和分子亚型的神经元中，几种经电生理学鉴定的 “eType” 中间神经元在注意力、学习和工作记忆任务中被募集。在非人类灵长类动物的前额叶皮质中，对局部回路有抑制作用的 eType 神经元对与行为相关的线索、意外结果进行编码，并调节工作记忆表征。这些反应特征与啮齿动物中 PV+、SST+ 和 VIP+ 中间神经元的功能特化相一致，这些中间神经元在注意力和记忆引导任务中被募集。我们探讨了这些关于中间神经元类型的功能研究是如何得到新开发的分子和分析工具支持的，以及如何受到计算研究的指导，这些计算研究表明不同类型的中间神经元具有独特的回路模式，可灵活地引导突触输入、计算预测误差并促进工作记忆中的信息保留。

REF: Boroujeni KB, Balaram P, Tiesinga P, Womelsdorf T. Prefrontal cortex interneurons and their contributions to attention, working memory, and adaptive behavior. Prog Neurobiol. 2026;258:102873. doi:10.1016/j.pneurobio.2025.102873 PMID: 41478518

Molecular mechanisms of age-related vulnerability to traumatic brain injury

与年龄相关的创伤性脑损伤易感性的分子机制

Aging is associated with increased vulnerability to a wide variety of diseases and conditions, including traumatic brain injury (TBI). While advanced age is a known predictor of poorer outcomes following TBI, the molecular mechanisms underlying this susceptibility haven't been completely characterized. This review discusses some of the primary pathways and physiological changes that are affected by aging and how they influence the post-TBI recovery in both experimental and clinical settings. Some of the age-related alterations implicated in geriatric TBI include loss of white matter, compromised blood-brain-barrier integrity, aggravated oxidative stress, mitochondrial dysfunction, higher cell death and synapse loss, increased and more prolonged neuroinflammation, compromised neural repair mechanisms, dysregulated proteasomal degradation leading to misfolded protein aggregation, and systemic changes such as peripheral organ dysfunction. This review further focuses on how the underlying molecular mechanisms involved in these changes influence long-term functional and behavioral outcomes after TBI. Lastly, some of the current and potential therapeutic interventions for geriatric TBI have also been discussed.

衰老与多种疾病和状况的易感性增加有关，包括创伤性脑损伤（TBI）。虽然高龄是TBI后预后较差的已知预测因素，但这种易感性的分子机制尚未完全明确。本综述探讨了受衰老影响的一些主要通路和生理变化，以及它们在实验和临床环境中如何影响TBI后的恢复。与老年TBI相关的一些与年龄有关的改变包括白质丢失、血脑屏障完整性受损、氧化应激加剧、线粒体功能障碍、细胞死亡和突触丢失增加、神经炎症加剧且持续时间更长、神经修复机制受损、蛋白酶体降解失调导致错误折叠蛋白聚集，以及外周器官功能障碍等全身性变化。本综述进一步聚焦于这些变化所涉及的潜在分子机制如何影响TBI后的长期功能和行为预后。最后，还讨论了目前针对老年TBI的一些治疗干预措施以及潜在的治疗方法。

REF: Joshi P, Vemuganti R. Molecular mechanisms of age-related vulnerability to traumatic brain injury. Prog Neurobiol. 2026;258:102890. doi:10.1016/j.pneurobio.2026.102890 PMID: 41620071

The flexible synapse – How mossy fiber architecture adapts to changing needs

灵活的突触——苔藓纤维结构如何适应不断变化的需求

Hippocampal mossy fiber boutons are unique, highly plastic synapses within the hippocampal circuitry. Despite mossy fiber bouton's potential role in learning and memory processes, the precise underlying mechanisms leading to their strengthened synaptic connections are still not fully understood. Here, we provide an overview of the structural changes occurring during long-term potentiation of large presynaptic terminals formed by mossy fiber onto CA3 pyramidal cells. Such changes encompass (1) adaptations in the number, shape and size of the bouton; (2) changes in availability of synaptic vesicles as well as the number and occupancy of release sites within single boutons; and (3) nano-architectural changes in the molecular composition and spatial arrangements within active zones. We describe these changes and possible implications for mossy fiber function. Furthermore, we discuss open questions, current methodology, and possible future directions.

海马苔藓纤维终扣是海马神经回路中独特且具有高度可塑性的突触。尽管苔藓纤维终扣在学习和记忆过程中可能发挥作用，但导致其突触连接增强的确切潜在机制仍未完全明确。在此，我们概述了苔藓纤维与CA3锥体神经元形成的大型突触前终末在长时程增强过程中发生的结构变化。这些变化包括：（1）终扣数量、形状和大小的改变；（2）单个终扣内突触小泡的可利用性以及释放位点的数量和占据情况的变化；（3）活性区内分子组成和空间排列的纳米结构变化。我们描述了这些变化及其对苔藓纤维功能的可能影响。此外，我们还讨论了悬而未决的问题、当前的研究方法以及未来可能的研究方向。

REF: Bruentgens F, Schmitz D, Orlando M. The flexible synapse - How mossy fiber architecture adapts to changing needs. Prog Neurobiol. 2026;258:102882. doi:10.1016/j.pneurobio.2026.102882 PMID: 41587599