Multimodal mapping of macaque monkey somatosensory cortex

猕猴体感皮层的多模态映射

The somatosensory cortex is a brain region responsible for receiving and processing sensory information from across the body and is structurally and functionally heterogeneous. Since the chemoarchitectonic segregation of the cerebral cortex can be revealed by transmitter receptor distribution patterns, by using a quantitative multireceptor architectonical analysis, we determined the number and extent of distinct areas of the macaque somatosensory cortex. We identified three architectonically distinct cortical entities within the primary somatosensory cortex (i.e., 3bm, 3bli, 3ble), four within the anterior parietal cortex (i.e., 3am, 3al, 1 and 2) and six subdivisions (i.e., S2l, S2m, PVl, PVm, PRl and PRm) within the lateral fissure. We provide an ultra-high resolution 3D atlas of macaque somatosensory areas in stereotaxic space, which integrates cyto- and receptor architectonic features of identified areas. Multivariate analyses of the receptor fingerprints revealed four clusters of identified areas based on the degree of (dis)similarity of their receptor architecture. Each of these clusters can be associated with distinct levels of somatosensory processing, further demonstrating that the functional segregation of cortical areas is underpinned by differences in their molecular organization.

体感皮层是负责接收和处理来自整个身体的感觉信息的大脑区域，并且在结构和功能上是异质的。由于可以通过递质受体分布模式揭示大脑皮层的化学结构隔离，因此通过使用定量多受体结构分析，我们确定了猕猴体感皮层不同区域的数量和范围。我们在初级体感皮层中确定了三个在结构上不同的皮质实体 (即，3bm，3bli，3ble)，前顶叶皮层内有四个 (即，上午3点、3al、1和2) 和六个细分 (即，S2l、S2m、PVl、PVm、PRl和PRm)。我们提供了立体定位空间中猕猴体感区域的超高分辨率3D图谱，该图谱整合了已识别区域的细胞和受体结构特征。受体指纹的多变量分析显示，根据其受体结构的 (不) 相似性程度，确定了四个已识别区域的簇。这些簇中的每一个都可以与不同水平的体感处理相关联，进一步证明了皮质区域的功能分离是由其分子组织的差异所支撑的。

REF: Niu M, Rapan L, Froudist-Walsh S, et al. Multimodal mapping of macaque monkey somatosensory cortex. Prog Neurobiol. 2024;239:102633. doi:10.1016/j.pneurobio.2024.102633 PMID: 38830482

Experience-dependent regulation of dopaminergic signaling in the somatosensory cortex

躯体感觉皮层中多巴胺能信号的经验依赖性调节

Dopamine critically influences reward processing, sensory perception, and motor control. Yet, the modulation of dopaminergic signaling by sensory experiences is not fully delineated. Here, by manipulating sensory experience using bilateral single-row whisker deprivation, we demonstrated that gene transcription in the dopaminergic signaling pathway (DSP) undergoes experience-dependent plasticity in both granular and supragranular layers of the primary somatosensory (barrel) cortex (S1). Sensory experience and deprivation compete for the regulation of DSP transcription across neighboring cortical columns, and sensory deprivation-induced changes in DSP are topographically constrained. These changes in DSP extend beyond cortical map plasticity and influence neuronal information processing. Pharmacological regulation of D2 receptors, a key component of DSP, revealed that D2 receptor activation suppresses excitatory neuronal excitability, hyperpolarizes the action potential threshold, and reduces the instantaneous firing rate. These findings suggest that the dopaminergic drive originating from midbrain dopaminergic neurons, targeting the sensory cortex, is subject to experience-dependent regulation and might create a regulatory feedback loop for modulating sensory processing. Finally, using topological gene network analysis and mutual information, we identify the molecular hubs of experience-dependent plasticity of DSP. These findings provide new insights into the mechanisms by which sensory experience shapes dopaminergic signaling in the brain and might help unravel the sensory deficits observed after dopamine depletion.

多巴胺严重影响奖励处理，感官知觉和运动控制。然而，感觉体验对多巴胺能信号传导的调节尚未完全阐明。在这里，通过使用双侧单排晶须剥夺来操纵感觉体验，我们证明了多巴胺能信号通路 (DSP) 中的基因转录在初级体感 (桶状) 皮质 (S1) 的颗粒层和粒上层都经历了依赖于经验的可塑性。感觉体验和剥夺竞争跨邻近皮质柱的DSP转录的调节，并且感觉剥夺诱导的DSP变化在地形上受到限制。DSP的这些变化超出了皮质图的可塑性，并影响了神经元信息处理。D2受体的药理学调节是DSP的关键成分，表明D2受体激活可抑制兴奋性神经元兴奋性，使动作电位阈值超极化，并降低瞬时放电率。这些发现表明，源自中脑多巴胺能神经元的多巴胺能驱动，靶向感觉皮层，受到经验依赖性调节，并可能产生调节反馈回路来调节感觉处理。最后，利用拓扑基因网络分析和互信息，我们确定了DSP经验依赖可塑性的分子枢纽。这些发现为感觉体验影响大脑中多巴胺能信号传导的机制提供了新的见解，并可能有助于解开多巴胺耗竭后观察到的感觉缺陷。

REF: Jamal T, Yan X, Lantyer ADS, Ter Horst JG, Celikel T. Experience-dependent regulation of dopaminergic signaling in the somatosensory cortex. Prog Neurobiol. 2024;239:102630. doi:10.1016/j.pneurobio.2024.102630 PMID: 38834131

Calcium plays an essential role in early-stage dendrite injury detection and regeneration

钙在早期树突损伤检测和再生中起着至关重要的作用

Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their dendrites to initiate a pro-regenerative response has not yet been thoroughly investigated. Calcium plays a critical role in the early stages of axonal injury detection and is also indispensable for regeneration of the severed axon. Here, we report cell and neurite type-specific differences in laser injury-induced elevations of intracellular calcium levels. Using a human KCNJ2 transgene, we demonstrate that hyperpolarizing neurons only at the time of injury dampens dendrite regeneration, suggesting that inhibition of injury-induced membrane depolarization (and thus early calcium influx) plays a role in detecting and responding to dendrite injury. In exploring potential downstream calcium-regulated effectors, we identify L-type voltage-gated calcium channels, inositol triphosphate signaling, and protein kinase D activity as drivers of dendrite regeneration. In conclusion, we demonstrate that dendrite injury-induced calcium elevations play a key role in the regenerative response of dendrites and begin to delineate the molecular mechanisms governing dendrite repair.

树突在各种临床病症中受损，例如外伤性脑和脊髓损伤和卒中。神经元如何直接检测其树突的损伤以启动促再生反应尚未得到彻底研究。钙在轴突损伤检测的早期阶段起着至关重要的作用，并且对于切断的轴突的再生也是必不可少的。在这里，我们报告了激光损伤诱导的细胞内钙水平升高的细胞和神经突类型特异性差异。使用人KCNJ2转基因，我们证明超极化神经元仅在损伤时抑制树突再生，这表明抑制损伤诱导的膜去极化 (从而抑制早期钙流入) 在检测和响应树突损伤中起作用。在探索潜在的下游钙调节效应子时，我们确定了L型电压门控钙通道，三磷酸肌醇信号传导和蛋白激酶D活性是树突再生的驱动因素。总之，我们证明了树突损伤诱导的钙升高在树突的再生反应中起关键作用，并开始描述控制树突修复的分子机制。

REF: Duarte VN, Lam VT, Rimicci DS, Thompson-Peer KL. Calcium plays an essential role in early-stage dendrite injury detection and regeneration. Prog Neurobiol. 2024;239:102635. doi:10.1016/j.pneurobio.2024.102635 PMID: 38825174