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Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson’s disease
Subthalamic deep brain stimulation produces evoked resonant neural activity (ERNA) which has been linked to therapeutic benefit. Using a multimodal approach, the authors propose that ERNA reflects activation of the basal ganglia indirect pathway network.
- Leon A. Steiner
- , David Crompton
- & Luka Milosevic
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| Open Access
Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons
Connecting cerebral organoids with an axon bundle models inter-regional projections and enhances neural activity. Optogenetic stimulation induces short-term plasticity, offering insights into macroscopic circuit development and functionality.
- Tatsuya Osaki
- , Tomoya Duenki
- & Yoshiho Ikeuchi
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| Open Access
Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons
The health of brain cells is known to depend on functional autophagy, but the details are unclear. Here, the authors perform systematic proteomic profiling of human and mouse neurons, delineating the landscape of autophagy degradation in brain.
- Xiaoting Zhou
- , You-Kyung Lee
- & Zhenyu Yue
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Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex
Glial cells and their crosstalk after injury are crucial for brain regeneration. Here, the authors show the spatial, temporal, and single-cell responses of glial cells after injury and identify shared pathways controlling glial reactivity.
- Christina Koupourtidou
- , Veronika Schwarz
- & Jovica Ninkovic
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Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity
Long noncoding RNAs (lncRNAs) function in many processes yet their participation in learning is largely unknown. Here, we identify and characterize the lncRNA SLAMR, which is recruited to stimulated synapses to mediate structural plasticity during experience and fear memory consolidation.
- Isabel Espadas
- , Jenna L. Wingfield
- & Sathyanarayanan Puthanveettil
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| Open Access
Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes
SNARE-dependent membrane fusion underlies neurotransmission in the nervous system. Here, the authors demonstrate how, in mammalian neurons, the synaptic protein tomosyn controls secretion by increasing the energy barrier for fusion.
- Marieke Meijer
- , Miriam Öttl
- & Matthijs Verhage
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Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling
Here the authors report a method for cryogenic electron microscopy imaging of human brain tissue samples directly obtained from autopsy, offering insights into cellular ultrastructure and a tool to study potential pathologic features.
- Benjamin C. Creekmore
- , Kathryn Kixmoeller
- & Yi-Wei Chang
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| Open Access
Serotonergic modulation of vigilance states in zebrafish and mice
To successfully escape a predator, animals usually maintain a vigilance state, the neural basis of which was unknown. Here, authors show a 5-HT driven mechanism operating at neural circuit level which shapes the vigilance state in zebrafish and mice.
- Yang Zhao
- , Chun-Xiao Huang
- & Jianren Song
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| Open Access
The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
Mitochondria emerged as essential actors of neural circuits development. Here, the authors uncovered that the AMPK-related kinase NUAK1 controls axonal mitochondrial metabolism through the regulation of the mitochondrial microprotein BRAWNIN.
- Marine Lanfranchi
- , Sozerko Yandiev
- & Julien Courchet
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Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells
How the neighboring cells contribute to the survival and functions of neuronal cells remains elusive. Here, authors identified the cell-cell interactions between retinal ganglion cells (RGCs) and other cells after RGC injury and discovered the μ-opioid receptor promotes RGC resilience.
- Cheng Qian
- , Ying Xin
- & Jiang Qian
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| Open Access
Identification of the growth cone as a probe and driver of neuronal migration in the injured brain
Structure and functions of the tip of migratory neurons remain elusive. Here, the authors show that the PTPσ-expressing growth cone senses extracellular matrix changes and drives neuronal migration in the injured brain, leading to the functional recovery.
- Chikako Nakajima
- , Masato Sawada
- & Kazunobu Sawamoto
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Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo
The mechanisms regulating mitochondrial architecture in neurons remain unclear. The authors report that in dendrites, mitochondria structure is specified by the CAMKK2-AMPK pathway through compartment-specific and activity-dependent levels of fission.
- Daniel M. Virga
- , Stevie Hamilton
- & Tommy L. Lewis Jr
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| Open Access
A persistent prefrontal reference frame across time and task rules
The prefrontal cortex (PFC) is involved in rule-coding and long-term memory. Here, the authors identified a stably active neuronal ensemble in the mouse medial PFC in an olfaction-guided spatial memory task, which showed stable tuning to task features across time, rule-reversal, and context changes.
- Hannah Muysers
- , Hung-Ling Chen
- & Marlene Bartos
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| Open Access
A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution
The dorsal pons in the brainstem is packed with clusters of neurons, including the parabrachial nucleus, that are involved in many vital functions. Here, authors use single nucleus RNA sequencing and MERFISH to create a spatially defined transcriptional atlas of this region.
- Stefano Nardone
- , Roberto De Luca
- & Bradford B. Lowell
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Subfield-specific interneuron circuits govern the hippocampal response to novelty in male mice
Hippocampal GABAergic neurons are thought to play a role in processing memories. Here, the authors show that functions of parvalbumin and somatostatin expressing interneurons in mice depend on novelty and differ between hippocampal subfields.
- Thomas Hainmueller
- , Aurore Cazala
- & Marlene Bartos
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| Open Access
VAP spatially stabilizes dendritic mitochondria to locally support synaptic plasticity
Brain mitochondria serve as local energy supplies for synapses, and the mechanisms that stabilize mitochondria near dendritic spines are not fully understood. Here, the authors identify the vesicle-associated membrane protein-associated protein VAP as a mitochondrial stabilizer in spatially supporting synaptic plasticity.
- Ojasee Bapat
- , Tejas Purimetla
- & Vidhya Rangaraju
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Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis
Although functional interactions between receptors shape brain cell communication, their direct interaction remains elusive. Here, authors monitor the weak and transient interaction between NMDA and dopamine receptors, which tune synaptogenesis.
- Nathan Bénac
- , G. Ezequiel Saraceno
- & Laurent Groc
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| Open Access
ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function
Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome. Here the authors show this syndrome is associated with impaired white matter integrity, and that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function.
- Chang Hoon Cho
- , Ilana Vasilisa Deyneko
- & Bryen A. Jordan
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Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex
How aging affects the brain active milieu remains unknown. Here, the authors reveal atrophy and mitochondrial malfunction of astrocytes but not neurons in older human neocortex.
- Alexander Popov
- , Nadezda Brazhe
- & Alexey Semyanov
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Immunoproximity biotinylation reveals the axon initial segment proteome
The molecular composition of the axon initial segment (AIS) is not well defined. Here, the authors used a ratiometric immunoproximity labeling strategy on fixed wild-type rat neurons to identify the AIS proteome, including the scaffolding protein SCRIB.
- Wei Zhang
- , Yu Fu
- & Peng Zou
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| Open Access
Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex
How oligodendrocyte precursor cells (OPCs) integrate calcium signals and neuromodulatory cues to regulate fate is unclear. Here, the authors report that locomotion-induced norepinephrine release modulates OPC calcium dynamics and differentiation.
- Frederic Fiore
- , Khaleel Alhalaseh
- & Amit Agarwal
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| Open Access
Holistic bursting cells store long-term memory in auditory cortex
Previous work has identified cells in L2/3 of auditory cortex which strongly respond with bursting to a specific learned chord, but not to single component tones in an auditory task. Here the authors show that these cells correlate with the behavioral relevance of the learned composite sounds.
- Ruijie Li
- , Junjie Huang
- & Hongbo Jia
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| Open Access
INPP5D regulates inflammasome activation in human microglia
INPP5D/SHIP1 is a microglial-expressed gene that has been associated with Alzheimer’s disease through genetic studies. This study reveals that reduction in INPP5D activity induces activation of the NLRP3-inflammasome in human microglia.
- Vicky Chou
- , Richard V. Pearse II
- & Tracy L. Young-Pearse
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| Open Access
Online conversion of reconstructed neural morphologies into standardized SWC format
There are a number of programs available for digital reconstruction of neural morphology. Here the authors present a standardized specification of the SWC file format, and introduce xyz2swc, a tool that converts reconstruction formats described in the literature into the SWC standard.
- Ketan Mehta
- , Bengt Ljungquist
- & Giorgio A. Ascoli
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Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles
Using single-molecule super-resolution microscopy, researchers revealed that Tau controls the recycling pool of synaptic vesicles in hippocampal neurons by forming nanoscale biomolecular condensates that are dynamically regulated by neuronal activity.
- Shanley F. Longfield
- , Mahdie Mollazade
- & Ramón Martínez-Mármol
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| Open Access
Rapid threat assessment in the Drosophila thermosensory system
Animals are more likely to react to rapid rather than slow temperature change. Here, the authors identify a brain circuit in Drosophila that selectively responds to rapid thermal change, priming behavior for escape.
- Genevieve C. Jouandet
- , Michael H. Alpert
- & Marco Gallio
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| Open Access
Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer’s disease mouse model
The mechanisms that confer cognitive resilience to Alzheimer’s disease are not fully understood. Here, the authors uncover the role of the nucleus reuniens in promoting resilience through the suppression of hyperexcitability and the restoration of circuit-level homeostasis to prevent memory decline.
- Shiri Shoob
- , Nadav Buchbinder
- & Inna Slutsky
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Neuronal connected burst cascades bridge macroscale adaptive signatures across arousal states
Here the authors describe a biophysical layer-5 pyramidal neuronal model linking microscale spiking to macroscale complex dynamics, that predicts distinct burst dynamics and information processing across unconscious, dreaming, and awake states.
- Brandon R. Munn
- , Eli J. Müller
- & James M. Shine
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Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments
Few resident cell surface proteins have been identified at the axon initial segment. Here, Ogawa and colleagues use proximity labeling and proteomics to identify Contactin-1 as a transmembrane axon initial segment protein that regulates brain wiring.
- Yuki Ogawa
- , Brian C. Lim
- & Matthew N. Rasband
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Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication
Exposure to cannabis in adolescence is associated with increased risk of psychiatric disorders. Here, in a mouse model of 16p11.2 duplication, the authors identified a role of microglial Cnr1 for mediating the adverse effect of THC exposure on mPFC maturation and social memory.
- Yuto Hasegawa
- , Juhyun Kim
- & Atsushi Kamiya
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Discrete hippocampal projections are differentially regulated by parvalbumin and somatostatin interneurons
Discrete hippocampal cell types differentially regulate behavior. Here authors show that parvalbumin and somatostatin interneurons differentially innervate and regulate pyramidal cell projections, providing a potential circuit mechanism underlying hippocampal control of behavior.
- Daniel J. Lodge
- , Hannah B. Elam
- & Jennifer J. Donegan
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O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations
The neurofilament cytoskeleton is critical for axon function and can be dysregulated in disease. Here, the authors show that intracellular glycosylation regulates a key neurofilament protein.
- Duc T. Huynh
- , Kalina N. Tsolova
- & Michael Boyce
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Descending GABAergic pathway links brain sugar-sensing to peripheral nociceptive gating in Drosophila
Escape behavior is dynamically altered by animals’ physiological conditions. Here, the authors identify in Drosophila larvae a cluster of GABAergic descending neurons that mediate nociceptive modulation upon nutritional changes.
- Mami Nakamizo-Dojo
- , Kenichi Ishii
- & Kazuo Emoto
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| Open Access
Shadow imaging for panoptical visualization of brain tissue in vivo
Brain morphology is complex, heterogenous and miniaturized—and notoriously difficult to visualize. Dembitskaya et al. show how fluorescence ‘shadow imaging’ gives detailed and comprehensive access to the cellular architecture of the mouse brain in vivo.
- Yulia Dembitskaya
- , Andrew K. J. Boyce
- & U. Valentin Nägerl
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| Open Access
Polarized microtubule remodeling transforms the morphology of reactive microglia and drives cytokine release
Microglia drastically change their morphology when reacting to pathological stimuli. Here, the authors study the molecular responses to stimulation and unravel cytoskeleton remodeling pathways that induce morphological and functional changes.
- Max Adrian
- , Martin Weber
- & Casper C. Hoogenraad
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| Open Access
VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation
How the leptomeninges establish CNS compartments with different accessibility to immune cells and immune mediators remains unknown. Here, the authors show junctional localization of VE-cadherin in arachnoid and pia mater cells, which allows to visualize potential barrier properties of the leptomeninges in vivo.
- Josephine A. Mapunda
- , Javier Pareja
- & Britta Engelhardt
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| Open Access
Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents
Prosaposin (PSAP) variants are linked to Parkinson’s disease (PD). Here, the authors report PSP changes in PD and lipid dyshomeostasis and PD-like phenotypes in mice lacking PSAP in dopamine neurons; PSAP overexpression counteracts experimental PD.
- Yachao He
- , Ibrahim Kaya
- & Per Svenningsson
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| Open Access
Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice
The role of lactate in the control of microglial function remains poorly investigated. Here, the authors show that lactate promotes lysosomal acidification in microglia, and that mice lacking the lactate transporter MCT4 in these cells display defective brain development and anxiety-like behavior.
- Katia Monsorno
- , Kyllian Ginggen
- & Rosa Chiara Paolicelli
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Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control
The role of synaptogenesis during the acquisition of goal-directed behaviors is unknown. Here, the authors show that learning-induced synaptogenesis in the adult mouse cortex is required to excite a specific circuit to adjust effort exertion.
- Francesco Paolo Ulloa Severino
- , Oluwadamilola O. Lawal
- & Cagla Eroglu
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| Open Access
Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1 epileptic encephalopathy
One third of all epilepsies are treatment-resistant. Here, the authors show in a genetic model of epilepsy that a repurposed drug can correct cell defects, brain circuits and seizure-like events by accelerating endocytosis.
- Katherine Bonnycastle
- , Katharine L. Dobson
- & Michael A. Cousin
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| Open Access
Heterogeneous receptor expression underlies non-uniform peptidergic modulation of olfaction in Drosophila
Neuropeptides are ancient modulators of neural signaling, but remain poorly understood. Here, the authors examine the neural and molecular substrates that enable a single neuropeptide to differentially modulate olfactory input to the Drosophila AL.
- Tyler R. Sizemore
- , Julius Jonaitis
- & Andrew M. Dacks
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| Open Access
Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling
A-kinase anchoring proteins (AKAPs) target protein kinase A to specific locations within the cell. Here, the authors identify SPHKAP as an AKAP that enriches protein kinase A near ER-plasma membrane contact sites in brain neurons.
- Nicholas C. Vierra
- , Luisa Ribeiro-Silva
- & James S. Trimmer
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| Open Access
Erythropoietin re-wires cognition-associated transcriptional networks
The mechanism and physiological role of brain-expressed Erythropoietin (EPO) is unclear. Here, authors show that the trajectory of pyramidal neurons is maneuvered by EPO, befitting the neurogenic hypothesis of alleviating mood, memory, and cognition.
- Manvendra Singh
- , Ying Zhao
- & Hannelore Ehrenreich
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Article
| Open Access
Reactivated endogenous retroviruses promote protein aggregate spreading
Endogenous retroviruses, or genomic relics of ancient viral infection, have been associated with certain neurodegenerative diseases. Here, Liu et al. report a pathway by which reactivated viral gene products contribute to intercellular protein aggregate spreading.
- Shu Liu
- , Stefanie-Elisabeth Heumüller
- & Ina M. Vorberg
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| Open Access
A parabrachial-hypothalamic parallel circuit governs cold defense in mice
The neural mechanisms responsible for cold defense regulation are still unclear. Here, authors show parallel thermogenic pathways from the brain stem to the hypothalamus work together to enable resilience to cold temperature exposure and hypothermia.
- Wen Z. Yang
- , Hengchang Xie
- & Wei L. Shen
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| Open Access
Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice
Brain mitochondria play crucial roles that influence cognition, yet their diversity is often overlooked. This study in mice identifies distinct mitochondrial phenotypes distributed as large-scale networks, accounting for a large portion of animal-to-animal behavioural variation.
- Ayelet M. Rosenberg
- , Manish Saggar
- & Martin Picard
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| Open Access
Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury
The cellular responses below the lesion remain unclear after spinal cord injury (SCI). Here, authors show region-heterogeneous responses in the SCI monkey by single-cell transcriptomics analysis and uncover the mechanism of scaffold-based SCI repair.
- Yongheng Fan
- , Xianming Wu
- & Jianwu Dai
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| Open Access
Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers
High neuronal proteostress can trigger the production of aggregate-filled exophers in C. elegans. Here authors show that such extrusion relies on aggregate-associated intermediate filaments and adaptors.
- Meghan Lee Arnold
- , Jason Cooper
- & Monica Driscoll
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Article
| Open Access
An open resource combining multi-contrast MRI and microscopy in the macaque brain
Linking microscale cellular structures to macroscale features of the brain is required to fully understand its structure and function. Here, the authors present a resource which combines multi-contrast microscopy and MRI of a single whole macaque brain to facilitate multimodal analyses.
- Amy F. D. Howard
- , Istvan N. Huszar
- & Karla L. Miller
Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila