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JOURNAL ARTICLE
Ben Vermaercke, Ryohei Iwata, Keimpe Wierda, Leïla Boubakar, Paula Rodriguez, Martyna Ditkowska, Vincent Bonin, Pierre Vanderhaeghen
Human brain ontogeny is characterized by a considerably prolonged neotenic development of cortical neurons and circuits. Neoteny is thought to be essential for the acquisition of advanced cognitive functions, which are typically altered in intellectual disability (ID) and autism spectrum disorders (ASDs). Human neuronal neoteny could be disrupted in some forms of ID and/or ASDs, but this has never been tested. Here, we use xenotransplantation of human cortical neurons into the mouse brain to model SYNGAP1 haploinsufficiency, one of the most prevalent genetic causes of ID/ASDs...
July 31, 2024: Neuron
#22
JOURNAL ARTICLE
Kuo-Sheng Lee, Alastair J Loutit, Dominica de Thomas Wagner, Mark Sanders, Mario Prsa, Daniel Huber
In mammals, action potentials fired by rapidly adapting mechanosensitive afferents are known to reliably time lock to the cycles of a vibration. How and where along the ascending neuraxis is the peripheral afferent temporal code transformed into a rate code are currently not clear. Here, we probed the encoding of vibrotactile stimuli with electrophysiological recordings along major stages of the ascending somatosensory pathway in mice. We discovered the main transformation step was identified at the level of the thalamus, and parvalbumin-positive interneurons in thalamic reticular nucleus participate in sharpening frequency selectivity and in disrupting the precise spike timing...
July 31, 2024: Neuron
#23
Soo Yeun Lee, Konstantinos Kozalakis, Fahimeh Baftizadeh, Luke Campagnola, Tim Jarsky, Christof Koch, Costas A Anastassiou
No abstract text is available yet for this article.
July 26, 2024: Neuron
#24
JOURNAL ARTICLE
Luyu Fan, Youwen Zhuang, Hongyu Wu, Huiqiong Li, Youwei Xu, Yue Wang, Licong He, Shishan Wang, Zhangcheng Chen, Jianjun Cheng, H Eric Xu, Sheng Wang
Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a β-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus β-arrestin coupling...
July 25, 2024: Neuron
#25
JOURNAL ARTICLE
Keith R Murphy, Jordan S Farrell, Jonas Bendig, Anish Mitra, Charlotte Luff, Ina A Stelzer, Hiroshi Yamaguchi, Christopher C Angelakos, Mihyun Choi, Wenjie Bian, Tommaso DiIanni, Esther Martinez Pujol, Noa Matosevich, Raag Airan, Brice Gaudillière, Elisa E Konofagou, Kim Butts-Pauly, Ivan Soltesz, Luis de Lecea
Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types...
July 24, 2024: Neuron
#26
JOURNAL ARTICLE
Isabel Lam, Alain Ndayisaba, Amanda J Lewis, YuHong Fu, Giselle T Sagredo, Anastasia Kuzkina, Ludovica Zaccagnini, Meral Celikag, Jackson Sandoe, Ricardo L Sanz, Aazam Vahdatshoar, Timothy D Martin, Nader Morshed, Toru Ichihashi, Arati Tripathi, Nagendran Ramalingam, Charlotte Oettgen-Suazo, Theresa Bartels, Manel Boussouf, Max Schäbinger, Erinc Hallacli, Xin Jiang, Amrita Verma, Challana Tea, Zichen Wang, Hiroyuki Hakozaki, Xiao Yu, Kelly Hyles, Chansaem Park, Xinyuan Wang, Thorold W Theunissen, Haoyi Wang, Rudolf Jaenisch, Susan Lindquist, Beth Stevens, Nadia Stefanova, Gregor Wenning, Wilma D J van de Berg, Kelvin C Luk, Rosario Sanchez-Pernaute, Juan Carlos Gómez-Esteban, Daniel Felsky, Yasujiro Kiyota, Nidhi Sahni, S Stephen Yi, Chee Yeun Chung, Henning Stahlberg, Isidro Ferrer, Johannes Schöneberg, Stephen J Elledge, Ulf Dettmer, Glenda M Halliday, Tim Bartels, Vikram Khurana
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC "inclusionopathy" models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions and their effects on cell survival were trackable at single-inclusion resolution. Exemplar cortical neuron α-synuclein inclusionopathy models were engineered through transgenic expression of α-synuclein mutant forms or exogenous seeding with fibrils...
July 23, 2024: Neuron
#27
JOURNAL ARTICLE
Hannah Scheiblich, Frederik Eikens, Lena Wischhof, Sabine Opitz, Kay Jüngling, Csaba Cserép, Susanne V Schmidt, Jessica Lambertz, Tracy Bellande, Balázs Pósfai, Charlotte Geck, Jasper Spitzer, Alexandru Odainic, Sergio Castro-Gomez, Stephanie Schwartz, Ibrahim Boussaad, Rejko Krüger, Enrico Glaab, Donato A Di Monte, Daniele Bano, Ádám Dénes, Eike Latz, Ronald Melki, Hans-Christian Pape, Michael T Heneka
Microglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson's and Alzheimer's disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health...
July 23, 2024: Neuron
#28
JOURNAL ARTICLE
Frédéric Villéga, Alexandra Fernandes, Julie Jézéquel, Floriane Uyttersprot, Nathan Benac, Sarra Zenagui, Laurine Bastardo, Hélène Gréa, Delphine Bouchet, Léa Villetelle, Olivier Nicole, Véronique Rogemond, Jérôme Honnorat, Julien P Dupuis, Laurent Groc
Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological and psychiatric conditions, tuning NMDAR synaptic trapping to assess its clinical relevance for the treatment of brain conditions remains a challenge. Here, we report that ketamine (KET) and other clinically relevant NMDAR open channel blockers (OCBs) promote interactions between NMDAR and PDZ-domain-containing scaffolding proteins and enhance NMDAR trapping at synapses...
July 17, 2024: Neuron
#29
JOURNAL ARTICLE
Ming Li, Xue-Ke Yang, Jian Yang, Tong-Xia Li, Chi Cui, Xiang Peng, Jie Lei, Kun Ren, Jie Ming, Pei Zhang, Bo Tian
Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells...
July 16, 2024: Neuron
#30
JOURNAL ARTICLE
Amanda H Lewis, Marie E Cronin, Jörg Grandl
Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P ) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here, we use chemical control to acutely restrict Piezo1 conformational flexibility and show that Piezo1 conformational changes, but not ion permeation through them, are required for modulating the K2P channel K2P 2...
July 12, 2024: Neuron
#31
JOURNAL ARTICLE
Ruchira M Jha, Dhivyaa Rajasundaram, Chaim Sneiderman, Brent T Schlegel, Casey O'Brien, Zujian Xiong, Keri Janesko-Feldman, Ria Trivedi, Vincent Vagni, Benjamin E Zusman, Joshua S Catapano, Adam Eberle, Shashvat M Desai, Ashutosh P Jadhav, Sandra Mihaljevic, Margaux Miller, Sudhanshu Raikwar, Anupama Rani, Jarrod Rulney, Shima Shahjouie, Itay Raphael, Aditya Kumar, Chia-Ling Phuah, Ethan A Winkler, Dennis W Simon, Patrick M Kochanek, Gary Kohanbash
Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution...
July 11, 2024: Neuron
#32
JOURNAL ARTICLE
Rhian Stavely, Ahmed A Rahman, Jessica L Mueller, Abigail R Leavitt, Christopher Y Han, Weikang Pan, Kyla N Kaiser, Leah C Ott, Takahiro Ohkura, Richard A Guyer, Alan J Burns, Abigail N Koppes, Ryo Hotta, Allan M Goldstein
Here, we establish that plasticity exists within the postnatal enteric nervous system by demonstrating the reinnervation potential of post-mitotic enteric neurons (ENs). Employing BAF53b-Cre mice for selective neuronal tracing, the reinnervation capabilities of mature postnatal ENs are shown across multiple model systems. Isolated ENs regenerate neurites in vitro, with neurite complexity and direction influenced by contact with enteric glial cells (EGCs). Nerve fibers from transplanted ENs exclusively interface and travel along EGCs within the muscularis propria...
July 10, 2024: Neuron
#33
JOURNAL ARTICLE
Zhenggang Zhu, Lu Miao, Kaiyuan Li, Qingqing Ma, Lina Pan, Chenjie Shen, Qianqian Ge, Yonglan Du, Luping Yin, Hongbin Yang, Xiaohong Xu, Ling-Hui Zeng, Yijun Liu, Han Xu, Xiao-Ming Li, Li Sun, Yan-Qin Yu, Shumin Duan
Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice...
July 10, 2024: Neuron
#34
JOURNAL ARTICLE
Adam J Eisen, Leo Kozachkov, André M Bastos, Jacob A Donoghue, Meredith K Mahnke, Scott L Brincat, Sarthak Chandra, John Tauber, Emery N Brown, Ila R Fiete, Earl K Miller
Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs)...
July 10, 2024: Neuron
#35
JOURNAL ARTICLE
Xuewen Cheng, Miao Zhao, Lei Chen, Chenwei Huang, Qiwu Xu, Jia Shao, Hong-Tao Wang, Yuxian Zhang, Xuequan Li, Xuan Xu, Xiang-Ping Yao, Kai-Jun Lin, Hui Xue, Han Wang, Qi Chen, Yong-Chuan Zhu, Jia-Wei Zhou, Woo-Ping Ge, Shu-Jia Zhu, Jing-Yu Liu, Wan-Jin Chen, Zhi-Qi Xiong
Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1...
July 9, 2024: Neuron
#36
JOURNAL ARTICLE
Matteo Carandini
Logistic classification is a simple way to make choices based on a set of factors: give each factor a weight, sum the results, and use the sum to set the log odds of a random draw. This operation is known to describe human and animal choices based on value (economic decisions). There is increasing evidence that it also describes choices based on sensory inputs (perceptual decisions), presented across sensory modalities (multisensory integration) and combined with non-sensory factors such as prior probability, expected value, overall motivation, and recent actions...
July 9, 2024: Neuron
#37
JOURNAL ARTICLE
Yoshimitsu Nakanishi, Mayuko Izumi, Hiroaki Matsushita, Yoshihisa Koyama, Diego Diez, Hyota Takamatsu, Shohei Koyama, Masayuki Nishide, Maiko Naito, Yumiko Mizuno, Yuta Yamaguchi, Tomoki Mae, Yu Noda, Kamon Nakaya, Satoshi Nojima, Fuminori Sugihara, Daisuke Okuzaki, Masahito Ikawa, Shoichi Shimada, Sujin Kang, Atsushi Kumanogoh
Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis. Using genome-wide approaches, we identify SEMA6D as a pleiotropic gene for both psychiatric and metabolic traits in human. Sema6d deficiency increases anxiety in mice...
July 9, 2024: Neuron
#38
JOURNAL ARTICLE
Corbett Bennett, Ben Ouellette, Tamina K Ramirez, Alex Cahoon, Hannah Cabasco, Yoni Browning, Anna Lakunina, Galen F Lynch, Ethan G McBride, Hannah Belski, Ryan Gillis, Conor Grasso, Robert Howard, Tye Johnson, Henry Loeffler, Heston Smith, David Sullivan, Allison Williford, Shiella Caldejon, Severine Durand, Samuel Gale, Alan Guthrie, Vivian Ha, Warren Han, Ben Hardcastle, Chris Mochizuki, Arjun Sridhar, Lucas Suarez, Jackie Swapp, Joshua Wilkes, Joshua H Siegle, Colin Farrell, Peter A Groblewski, Shawn R Olsen
To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. Although new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe skull-shaped hemispheric implants enabling large-scale electrophysiology datasets (SHIELD). These 3D-printed skull-replacement implants feature customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days...
July 8, 2024: Neuron
#39
REVIEW
Richard H Roth, Jun B Ding
One key function of the brain is to control our body's movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain's motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills...
July 4, 2024: Neuron
#40
JOURNAL ARTICLE
Qiang Jiang, Wenjuan Zou, Shitian Li, Xufeng Qiu, Linhui Zhu, Lijun Kang, Ulrich Müller
Transmembrane channel-like (TMC) proteins are expressed throughout the animal kingdom and are thought to encode components of ion channels. Mammals express eight TMCs (mTMC1-8), two of which (mTMC1 and mTMC2) are subunits of mechanotransduction channels. C. elegans expresses two TMCs (TMC-1 and TMC-2), which mediate mechanosensation, egg laying, and alkaline sensing. The mechanisms by which nematode TMCs contribute to such diverse physiological processes and their functional relationship to mammalian mTMCs is unclear...
July 3, 2024: Neuron
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