Morten L Kringelbach, Peter Vuust, Gustavo Deco
"Supporting human flourishing" is a goal of governments and societies, yet the construct may appear hard to define. We discuss the emerging science of pleasure and flourishing, insights into the brain mechanisms of meaning making and thriving, and the potential for interdisciplinary studies to advance this promising scientific field.
April 5, 2024: Neuron
Mar Márquez-Ropero, Amanda Sierra
Removal of toxic debris that can hinder brain function is performed primarily by microglia, the brain's professional phagocytes. A recent study in Cell1 identified that viral response interferons are required for priming microglia, ensuring competent phagocytosis and proper circuit wiring.
April 2, 2024: Neuron
Degan Mesler, Vicki Campbell
Scientists face challenges in communicating about their careers in biomedical research to the public, despite the importance of doing so. Here, we discuss tools and resources for outreach, such as posters, videos, and presentations that can be leveraged by scientists to help educate communities about the pivotal role of animals in medical progress.
April 2, 2024: Neuron
Laura Mòdol, Monika Moissidis, Martijn Selten, Fazal Oozeer, Oscar Marín
Synchronous neuronal activity is a hallmark of the developing brain. In the mouse cerebral cortex, activity decorrelates during the second week of postnatal development, progressively acquiring the characteristic sparse pattern underlying the integration of sensory information. The maturation of inhibition seems critical for this process, but the interneurons involved in this crucial transition of network activity in the developing cortex remain unknown. Using in vivo longitudinal two-photon calcium imaging during the period that precedes the change from highly synchronous to decorrelated activity, we identify somatostatin-expressing (SST+) interneurons as critical modulators of this switch in mice...
April 2, 2024: Neuron
Saptarshi Biswas, Sanjid Shahriar, Galina Bachay, Panos Arvanitis, Danny Jamoul, William J Brunken, Dritan Agalliu
Interactions among neuronal, glial, and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunction precedes vascular abnormalities in many retinal pathologies, how neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Using in vivo genetic studies in mice, single-cell RNA sequencing (scRNA-seq), and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas where neurons fail to release glutamate...
April 2, 2024: Neuron
George A Mashour
In the 19th century, the discovery of general anesthesia revolutionized medical care. In the 21st century, anesthetics have become indispensable tools to study consciousness. Here, I review key aspects of the relationship between anesthesia and the neurobiology of consciousness, including interfaces of sleep and anesthetic mechanisms, anesthesia and primary sensory processing, the effects of anesthetics on large-scale functional brain networks, and mechanisms of arousal from anesthesia. I discuss the implications of the data derived from the anesthetized state for the science of consciousness and then conclude with outstanding questions, reflections, and future directions...
March 27, 2024: Neuron
Dolores Irala, Shiyi Wang, Kristina Sakers, Leykashree Nagendren, Francesco Paolo Ulloa Severino, Dhanesh Sivadasan Bindu, Justin T Savage, Cagla Eroglu
Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an astrocyte-secreted inhibitory synaptogenic protein. After secretion from astrocytes, neurocan is cleaved into N- and C-terminal fragments. We found that these fragments have distinct localizations in the extracellular matrix...
March 27, 2024: Neuron
Sandra M V Kochan, Meret Cepero Malo, Milica Jevtic, Hannah M Jahn-Kelleter, Gulzar A Wani, Kristiano Ndoci, Laura Pérez-Revuelta, Felix Gaedke, Iris Schäffner, Dieter Chichung Lie, Astrid Schauss, Matteo Bergami
Integration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration and uniquely contribute to hippocampal function, immature neurons are endowed with a critical period of heightened synaptic plasticity, yet it remains unclear which mechanisms sustain this form of plasticity during neuronal maturation. We found that as new neurons enter their critical period, a transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies in dendrites to fuel synaptic plasticity...
March 26, 2024: Neuron
Jiesi Feng, Hui Dong, Julieta E Lischinsky, Jingheng Zhou, Fei Deng, Chaowei Zhuang, Xiaolei Miao, Huan Wang, Guochuan Li, Ruyi Cai, Hao Xie, Guohong Cui, Dayu Lin, Yulong Li
Norepinephrine (NE) is an essential biogenic monoamine neurotransmitter. The first-generation NE sensor makes in vivo, real-time, cell-type-specific and region-specific NE detection possible, but its low NE sensitivity limits its utility. Here, we developed the second-generation GPCR-activation-based NE sensors (GRABNE2m and GRABNE2h ) with a superior response and high sensitivity and selectivity to NE both in vitro and in vivo. Notably, these sensors can detect NE release triggered by either optogenetic or behavioral stimuli in freely moving mice, producing robust signals in the locus coeruleus and hypothalamus...
March 26, 2024: Neuron
Wei Ouyang, Keith J Kilner, Rachael M P Xavier, Yiming Liu, Yinsheng Lu, Sophia M Feller, Kayla M Pitts, Mingzheng Wu, Jokubas Ausra, Ian Jones, Yunyun Wu, Haiwen Luan, Jacob Trueb, Elizabeth M Higbee-Dempsey, Iwona Stepien, Nayereh Ghoreishi-Haack, Chad R Haney, Hao Li, Yevgenia Kozorovitskiy, Mitra Heshmati, Anthony R Banks, Sam A Golden, Cameron H Good, John A Rogers
Comprehensive, continuous quantitative monitoring of intricately orchestrated physiological processes and behavioral states in living organisms can yield essential data for elucidating the function of neural circuits under healthy and diseased conditions, for defining the effects of potential drugs and treatments, and for tracking disease progression and recovery. Here, we report a wireless, battery-free implantable device and a set of associated algorithms that enable continuous, multiparametric physio-behavioral monitoring in freely behaving small animals and interacting groups...
March 19, 2024: Neuron
Yiyao Zhang, Mursel Karadas, JingJing Liu, Xinyi Gu, Mihály Vöröslakos, Yulong Li, Richard W Tsien, György Buzsáki
A postulated role of subcortical neuromodulators is to control brain states. Mechanisms by which different neuromodulators compete or cooperate at various temporal scales remain an open question. We investigated the interaction of acetylcholine (ACh) and oxytocin (OXT) at slow and fast timescales during various brain states. Although these neuromodulators fluctuated in parallel during NREM packets, transitions from NREM to REM were characterized by a surge of ACh but a continued decrease of OXT. OXT signaling lagged behind ACh...
March 18, 2024: Neuron
Xu-Yi Li, Shi-Ya Zhang, Yi-Zhou Hong, Zhi-Gang Chen, Yan Long, Dan-Hua Yuan, Jia-Jia Zhao, Su-Su Tang, Hao Wang, Hao Hong
Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior...
March 12, 2024: Neuron
Denghong Zhang, Wei Zhang, Chen Ming, Xuheng Gao, Huilong Yuan, Xiaojie Lin, Xinru Mao, Chunping Wang, Xiaoyi Guo, Ying Du, Lin Shao, Renzhi Yang, Zhihao Lin, Xilin Wu, Timothy Y Huang, Zhanxiang Wang, Yun-Wu Zhang, Huaxi Xu, Yingjun Zhao
Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau...
March 12, 2024: Neuron
Yi-Zhe Huang, Jing-Xian Ma, Yu-Jing Bian, Qin-Ru Bai, Yu-Hao Gao, Shu-Ke Di, Yun-Tao Lei, Hui Yang, Xiao-Na Yang, Chang-Yan Shao, Wen-Hui Wang, Peng Cao, Chang-Zhu Li, Michael X Zhu, Meng-Yang Sun, Ye Yu
Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+ , Trpv1-/- , and Trpv1T634A/T634A . Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT...
March 11, 2024: Neuron
Spencer T Brown, Mauricio Medina-Pizarro, Meghana Holla, Christopher E Vaaga, Indira M Raman
Whisker stimulation in awake mice evokes transient suppression of simple spike probability in crus I/II Purkinje cells. Here, we investigated how simple spike suppression arises synaptically, what it encodes, and how it affects cerebellar output. In vitro, monosynaptic parallel fiber (PF)-excitatory postsynaptic currents (EPSCs) facilitated strongly, whereas disynaptic inhibitory postsynaptic currents (IPSCs) remained stable, maximizing relative inhibitory strength at the onset of PF activity. Short-term plasticity thus favors the inhibition of Purkinje spikes before PFs facilitate...
March 8, 2024: Neuron
Mark A Gradwell, Nofar Ozeri-Engelhard, Jaclyn T Eisdorfer, Olivier D Laflamme, Melissa Gonzalez, Aman Upadhyay, Laura Medlock, Tara Shrier, Komal R Patel, Adin Aoki, Melissa Gandhi, Gloria Abbas-Zadeh, Olisemaka Oputa, Joshua K Thackray, Matthew Ricci, Arlene George, Nusrath Yusuf, Jessica Keating, Zarghona Imtiaz, Simona A Alomary, Manon Bohic, Michael Haas, Yurdiana Hernandez, Steven A Prescott, Turgay Akay, Victoria E Abraira
Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input...
March 4, 2024: Neuron
Jason Manley, Sihao Lu, Kevin Barber, Jeffrey Demas, Hyewon Kim, David Meyer, Francisca Martínez Traub, Alipasha Vaziri
The brain's remarkable properties arise from the collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent" signals reflecting neural computations. However, can such low-dimensional representations truly explain the vast range of brain activity, and if not, what is the appropriate resolution and scale of recording to capture them? Imaging neural activity at cellular resolution and near-simultaneously across the mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number in populations up to 1 million neurons...
March 1, 2024: Neuron
Hankui Cheng, Du Chen, Xiao Li, Umar Al-Sheikh, Duo Duan, Yuedan Fan, Linhui Zhu, Wanxin Zeng, Zhitao Hu, Xiajing Tong, Guohua Zhao, Yongming Zhang, Wenjuan Zou, Shumin Duan, Lijun Kang
Phasic (fast) and tonic (sustained) inhibition of γ-aminobutyric acid (GABA) are fundamental for regulating day-to-day activities, neuronal excitability, and plasticity. However, the mechanisms and physiological functions of glial GABA transductions remain poorly understood. Here, we report that the AMsh glia in Caenorhabditis elegans exhibit both phasic and tonic GABAergic signaling, which distinctively regulate olfactory adaptation and neuronal aging. Through genetic screening, we find that GABA permeates through bestrophin-9/-13/-14 anion channels from AMsh glia, which primarily activate the metabolic GABAB receptor GBB-1 in the neighboring ASH sensory neurons...
March 1, 2024: Neuron
Bianca Graziano, Lei Wang, Olivia R White, Daryn H Kaplan, Jesus Fernandez-Abascal, Laura Bianchi
KCNQs are voltage-gated K+ channels that control neuronal excitability and are mutated in epilepsy and autism spectrum disorder (ASD). KCNQs have been extensively studied in neurons, but their function in glia is unknown. Using voltage, calcium, and GABA imaging, optogenetics, and behavioral assays, we show here for the first time in Caenorhabditis elegans (C. elegans) that glial KCNQ channels control neuronal excitability by mediating GABA release from glia via regulation of the function of L-type voltage-gated Ca2+ channels...
February 29, 2024: Neuron
K A Agyeman, D J Lee, J Russin, E I Kreydin, W Choi, A Abedi, Y T Lo, J Cavaleri, K Wu, V R Edgerton, C Liu, V N Christopoulos
Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized...
February 29, 2024: Neuron
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