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| Open AccessKalium channelrhodopsins effectively inhibit neurons
Kalium channelrhodopsins (KCRs) are promising tools for optogenetic silencing. Here, the authors show that KCRs inhibit cellular excitability in flies, worms, and fish, establishing them as first-line tools for inhibiting diverse types of excitable cells.
- Stanislav Ott
- , Sangyu Xu
- & Adam Claridge-Chang
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Article
| Open AccessSilencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations
Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1.
- Chinnakkaruppan Adaikkan
- , Justin Joseph
- & Thomas J. McHugh
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Article
| Open AccessDendritic mGluR2 and perisomatic Kv3 signaling regulate dendritic computation of mouse starburst amacrine cells
How starburst amacrine cell (SAC) dendrites transform concentrically distributed synaptic inputs into branch-specific directional outputs is not fully understood. Here the authors report that dendritic mGluR2 signaling and somatic Kv3-mediated shunting coordinately implement SAC dendritic direction selectivity.
- Héctor Acarón Ledesma
- , Jennifer Ding
- & Wei Wei
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Article
| Open AccessInduced neural phase precession through exogenous electric fields
The neural mechanisms underpinning phase precession remain poorly understood. Here, the authors demonstrate that exogenously generated oscillatory electric fields in the brain can induce phase precession-like effects on cortical excitability and neural firing.
- Miles Wischnewski
- , Harry Tran
- & Alexander Opitz
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Article
| Open AccessSerotonin modulates excitatory synapse maturation in the developing prefrontal cortex
The role of serotonin in prefrontal cortex development remains unexplored. Here, authors show that serotonin regulates maturation and stabilization of prefrontal excitatory synapses.
- Roberto Ogelman
- , Luis E. Gomez Wulschner
- & Won Chan Oh
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Article
| Open AccessTransient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy
Epileptic seizures need better treatments. Here, the authors show that seizure intensity is predicted and controlled by pre-seizure activity of hypothalamic orexin cells, and can be reduced by a hypothalamic deep brain stimulation.
- Han-Tao Li
- , Paulius Viskaitis
- & Denis Burdakov
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| Open AccessAcetylcholine receptor based chemogenetics engineered for neuronal inhibition and seizure control assessed in mice
Traditional systematic anti-seizure treatments alter brain-wide activity and often carry significant side effects. The authors engineered an inhibitory, acetylcholine receptor-based, chemogenetic tool to suppress targeted neurons, enabling control of chronic seizures in mice.
- Quynh-Anh Nguyen
- , Peter M. Klein
- & Ivan Soltesz
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Article
| Open AccessEpilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability
CDKL5 deficiency disorder is one of the most common genetic forms of epilepsy. Here the authors show that a model of CDKL5 deficiency disorder involves a channelopathy of CACNA1E gain-of-function, molecularly linking two distinct single-gene developmental and epileptic encephalopathies.
- Marisol Sampedro-Castañeda
- , Lucas L. Baltussen
- & Sila K. Ultanir
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Article
| Open AccessHolistic 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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Article
| Open AccessPhox2b-expressing neurons contribute to breathing problems in Kcnq2 loss- and gain-of-function encephalopathy models
Kcnq2 disfunction can cause developmental and epileptic encephalopathy (DEE). Here, authors show loss or gain of Kcnq2 function in Phox2b-expressing neurons disrupts breathing, thus identifying these cells as a likely basis for DEE breathing problems.
- J. Soto-Perez
- , C. M. Cleary
- & D. K. Mulkey
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Article
| Open AccessDiversity of cortical activity changes beyond depression during Spreading Depolarizations
Spreading depolarizations are classically thought to be associated with depression of cortical activity. Here, authors show variable, from depression to booming, changes in cortical activity during different types of spreading depolarizations.
- Azat Nasretdinov
- , Daria Vinokurova
- & Roustem Khazipov
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Article
| Open AccessSynaptic mechanisms for associative learning in the cerebellar nuclei
The role of the cerebellar nuclei (CN) during associative learning remains debated. Here, the authors show that well-timed conditioned responses can result from stimulating CN inputs, and that learning coincides with structural and synaptic activity changes in vivo.
- Robin Broersen
- , Catarina Albergaria
- & Chris I. De Zeeuw
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Article
| Open AccessDaily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability
Ionic levels in neurons provide the potential energy for all neuronal communication. Here the. authors show a very large modulation of [Cl-]i neocortical pyramidal cells, from day to night, with marked effects on cortical excitability and processing.
- Enrico Pracucci
- , Robert T. Graham
- & Gian-Michele Ratto
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Article
| Open AccessIctogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice
Predicting seizure onsets may allow for seizure prevention in patients. Here, authors show two distinct phases that always preceded temporal lobe seizures in mice, with activity confined within these two phases failing to progress into a seizure.
- John-Sebastian Mueller
- , Fabio C. Tescarollo
- & Hai Sun
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Article
| Open AccessTraining-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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Article
| Open AccessModulatory dynamics of periodic and aperiodic activity in respiration-brain coupling
Respiration modulates neural oscillations, but its link to aperiodic brain activity is not known. With a multi-centre human MEG and EEG study, here the authors show that fluctuations of aperiodic brain activity are phase-locked to the respiratory cycle.
- Daniel S. Kluger
- , Carina Forster
- & Joachim Gross
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Article
| Open AccessIn situ assembly of bioresorbable organic bioelectronics in the brain
Temporary bioelectronics can complement classical therapies in non-chronic treatments. Here, the authors describe the minimally invasive implantation of bioresorbable electrodes in the brain that form in situ from water-dispersed nanoparticles and show no tissue damage after bioresorption.
- Martin Hjort
- , Abdelrazek H. Mousa
- & Roger Olsson
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Article
| Open AccessMitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons
SHLP2 is a mitochondrial-derived peptide that plays an important role in energy homeostasis. Here, the authors show SHLP2’s protective effect against obesity and its mechanisms of action by binding to CXCR7 and activating hypothalamic neurons that regulate food intake, energy expenditure, and glucose homeostasis.
- Seul Ki Kim
- , Le Trung Tran
- & Ki Woo Kim
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Article
| Open AccessStriatal cholinergic interneuron membrane voltage tracks locomotor rhythms in mice
Behaviorally relevant neural rhythms have been mainly studied at the neural population level. Here, the authors show that subthreshold membrane voltage delta-frequency oscillations in individual striatal cholinergic neurons modulate spike timing, striatal network beta rhythmicity, and track patterned stepping movement.
- Sanaya N. Shroff
- , Eric Lowet
- & Xue Han
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Article
| Open AccessAfferent convergence to a shared population of interneuron AMPA receptors
Glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. Here, the authors find in the cerebellar cortex that glutamate spillover from climbing fibers activates synaptic AMPA receptors of molecular layer interneurons, allowing glutamate from an unconnected pathway to co-opt postsynaptic receptors.
- Reagan L. Pennock
- , Luke T. Coddington
- & Jacques I. Wadiche
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Article
| Open AccessRole of TMEM100 in mechanically insensitive nociceptor un-silencing
Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.
- Timo A. Nees
- , Na Wang
- & Stefan G. Lechner
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Article
| Open AccessCocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice
The prefrontal cortex is involved in cocaine abuse disorders. Here, the authors show that cocaine suppresses frontal association cortex (FrA) in awake mice and induces locomotor sensitization through a dopamine dependent VTA-vmPFC-FrA pathway.
- Lun Wang
- , Min Gao
- & Zhuan Zhou
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Article
| Open AccessOptogenetic frequency scrambling of hippocampal theta oscillations dissociates working memory retrieval from hippocampal spatiotemporal codes
How temporal coordination of neurons in the hippocampus contributes to memory function is not well understood. Here the authors show that abolishing hippocampal theta oscillations lead to impaired working and episodic memory while leaving spatiotemporal codes intact.
- Guillaume Etter
- , Suzanne van der Veldt
- & Sylvain Williams
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Article
| Open AccessAn astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning
How glial cells like astrocytes shape complex brain functions remains unclear. Here, the authors identified an astrocyte-mediated excitatory signaling loop between neurons and their own dendritic signal integration that supports spatial memory.
- Kirsten Bohmbach
- , Nicola Masala
- & Christian Henneberger
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Article
| Open AccessTiltable objective microscope visualizes selectivity for head motion direction and dynamics in zebrafish vestibular system
Signals about head orientation and movement in the vestibular periphery are fundamental to the sense of balance and motion, but difficult to measure systematically during head motion. Here, the authors build a microscope that visualizes neural activity in hair cells and vestibular ganglion cells during 360° head tilt and vibration in zebrafish larvae, and reveal a topographic organization of direction- and static/dynamic stimulus-selective responses.
- Masashi Tanimoto
- , Ikuko Watakabe
- & Shin-ichi Higashijima
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Article
| Open AccessA nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
Maladaptive plastic changes in the brain are critical for pain maintenance. The authors identify a nigro–subthalamo–parabrachial pathway and reveal that reversing a series of neuronal and synaptic malfunctions in this pathway in acute and chronic pain mitigates hyperalgesia, providing potential therapeutic targets for pain modulation.
- Tao Jia
- , Ying-Di Wang
- & Chunyi Zhou
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Article
| Open AccessTagging active neurons by soma-targeted Cal-Light
Techniques for tagging active neurons with high spatiotemporal precision are limited. Here the authors report soma-targeted CalLight (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression, and generate a conditional ST-Cal-Light knock-in mouse.
- Jung Ho Hyun
- , Kenichiro Nagahama
- & Hyung-Bae Kwon
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Article
| Open AccessA glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling
Presynaptic homeostatic plasticity adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor functionality. Here the authors identify a calcium-independent signaling system where active CaMKII detects a short domain encoded in a glutamate receptor C-tail, which gates retrograde homeostatic communication at a model glutamatergic synapse.
- Sarah Perry
- , Yifu Han
- & Dion Dickman
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Article
| Open AccessGABAergic neurons in the rostromedial tegmental nucleus are essential for rapid eye movement sleep suppression
The neural circuits regulating REM sleep are poorly understood. The authors reveal that GABAergic neurons in the rostromedial tegmental nucleus suppress the onset and maintenance of REM sleep, and that projections of these neurons to the LDT and LH mediate distinct REM sleep transitions.
- Ya-Nan Zhao
- , Jian-Bo Jiang
- & Su-Rong Yang
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Article
| Open AccessA circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance
Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.
- Jing-Jing Yan
- , Xiao-Jing Ding
- & Xiao-Hong Xu
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Article
| Open AccessSharp-wave ripple doublets induce complex dendritic spikes in parvalbumin interneurons in vivo
The influence of sharp-wave ripples (SPW-Rs) on dendritic computation remains poorly understood. Here, the authors demonstrate the existence of SPW-R associated, branch-specific, dendritic spikes which serve as a temporal and spatial coincidence detectors during SPW-R-doublets in PV+ interneuron dendrites of awake mice.
- Linda Judák
- , Balázs Chiovini
- & Balázs Rózsa
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Article
| Open AccessCone opponent functional domains in primary visual cortex combine signals for color appearance mechanisms
Psychophysical studies predict that retinal cone-opponent mechanisms interact in specific combinations to generate color perception. Here, the authors show that the predicted interactions are implemented by organized circuits in primary visual cortex.
- Peichao Li
- , Anupam K. Garg
- & Edward M. Callaway
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Article
| Open AccessCell-specific regulation of gene expression using splicing-dependent frameshifting
Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.
- Jonathan P. Ling
- , Alexei M. Bygrave
- & Seth Blackshaw
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Article
| Open AccessLipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion
During hypoglycemia, glucagon secretion is part of the mechanism needed to restore normal blood glucose levels. Here, Strembitska et al. report that sensing of hypoglycemia by AgRP neurons requires Agpat5, an enzyme which prevents fatty acids from entering the mitochondria for ATP production, ensuring correct neuronal activation and glucagon secretion.
- Anastasiya Strembitska
- , Gwenaël Labouèbe
- & Bernard Thorens
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Article
| Open AccessQuasAr Odyssey: the origin of fluorescence and its voltage sensitivity in microbial rhodopsins
The authors present an in-depth investigation of excited state dynamics and molecular mechanism of the voltage sensing in microbial rhodopsins. Using a combination of spectroscopic investigations and molecular dynamics simulations, the study proposes the voltage-modulated deprotonation of the chromophore as the key event in the voltage sensing. Thus, molecular constraints that may further improve the fluorescence quantum yield and the voltage sensitivity are presented.
- Arita Silapetere
- , Songhwan Hwang
- & Peter Hegemann
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Article
| Open AccessFunctional neuronal circuitry and oscillatory dynamics in human brain organoids
Brain organoids replicate cellular organization found in the developing human brain. Here, the authors utilize microelectronics to map activity in brain organoids and assemble functional circuits that mirror complexity found in brain networks in vivo.
- Tal Sharf
- , Tjitse van der Molen
- & Kenneth S. Kosik
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| Open AccessTiming is everything: structural insights into the disease-linked Kv3 channels controlling fast action-potential firing in the brain
Kv3 channels enable neurons to fire at very high frequencies (>100 Hz) which is fundamental to brain development and our ability to make sense of the world at large. Cryo-EM and structure-function studies by Chi et al. now uncover Kv3 channel gating mechanisms and support new precision medicine approaches for CNS diseases.
- Martin J. Gunthorpe
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Article
| Open AccessSex-specific regulation of inhibition and network activity by local aromatase in the mouse hippocampus
Using a combination of molecular, genetic, functional and behavioural tools, this study describes the impact of brain synthesized estrogen in inhibitory neuronal function, network oscillations and hippocampal dependent memory.
- Alicia Hernández-Vivanco
- , Nuria Cano-Adamuz
- & Pablo Méndez
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Article
| Open AccessC. elegans enteric motor neurons fire synchronized action potentials underlying the defecation motor program
Most neurons in the nematode C. elegans communicate in an analog manner. Here, the authors demonstrate that enteric motor neurons can fire all-or-none action potentials, and that this digital communication is important for defecation.
- Jingyuan Jiang
- , Yifan Su
- & Qiang Liu
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Article
| Open AccessGq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice
The authors study mechanisms underlying neuromodulatory control of transitions between brain and behavioral states. They identify a mechanism whereby modulation of Gq activity in basolateral amygdala parvalbumin interneurons mediates the transition to a fear-associated network and behavioral state.
- Xin Fu
- , Eric Teboul
- & Jeffrey G. Tasker
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Article
| Open AccessMultichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation
Researchers from Freiburg University developed an ultraflexible fiber-based 3D light delivery system for electrophysiology and optogenetic manipulation in freely moving animals. The system allows multiside modulation of neuronal activity combined with neuronal measurements.
- David Eriksson
- , Artur Schneider
- & Ilka Diester
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Article
| Open AccessColocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe
Simultaneous neural activation and inhibition in the same brain region of animals is highly desirable. Here the authors report a wireless, dual-colour optogenetic probe with the co-expression of two spectrally distinct opsins to allow for bidirectional neuronal activity manipulation in a rodent model.
- Lizhu Li
- , Lihui Lu
- & Xing Sheng
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Article
| Open AccessPhysiological synaptic activity and recognition memory require astroglial glutamine
The authors present a fluorescent probe that tracks glutamine in live cells. They demonstrate the capabilities of the probe by providing direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions.
- Giselle Cheung
- , Danijela Bataveljic
- & Nathalie Rouach
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Article
| Open AccessTwo opposing hippocampus to prefrontal cortex pathways for the control of approach and avoidance behaviour
The authors reveal a mechanism for regulation of behaviour during approach avoidance conflicts that relies on two specialized, parallel circuits that allow bidirectional hippocampal control of the prefrontal cortex.
- Candela Sánchez-Bellot
- , Rawan AlSubaie
- & Andrew F. MacAskill
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Article
| Open AccessTrpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice
The authors show that Trpm5, but not Trpm4, is the main Na+ -permeant channel mediating the warmth-activated ICaN in lumbar motoneurons. Trpm5 is also critical in generating plateau potentials in bistable motoneurons that are essential for producing a postural tone in hindlimbs and amplifying the locomotor output.
- Rémi Bos
- , Benoît Drouillas
- & Frédéric Brocard
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Article
| Open AccessResurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control
The zebra finch robust nucleus of the arcopallium (RA) directs singing by providing descending projections to brainstem motor neurons. The authors show that electrophysiological characteristics of RA neurons rely on resurgent Na+ currents that emerge early during song development only in males.
- Benjamin M. Zemel
- , Alexander A. Nevue
- & Henrique von Gersdorff
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Article
| Open AccessThe paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice
Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor drive binge alcohol drinking and anxiety. The authors describe a complex feedforward inhibitory PVTVGLUT2-BNSTCRF circuit in mice that plays sex-dependent roles in alcohol drinking and avoidance behavior.
- Olivia B. Levine
- , Mary Jane Skelly
- & Kristen E. Pleil
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Article
| Open AccessPlace fields of single spikes in hippocampus involve Kcnq3 channel-dependent entrainment of complex spike bursts
Hippocampal pyramidal cells encode an animal’s location by single action potentials and complex spike bursts. The authors show that Kcnq3-containing M-channels synergistically with GABAergic inputs coordinate complex spike bursts during theta oscillations, which is a key mechanism for spatial coding by single spikes.
- Xiaojie Gao
- , Franziska Bender
- & Alexey Ponomarenko
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Article
| Open AccessCognitive functions and underlying parameters of human brain physiology are associated with chronotype
How being a “morning person” or “evening person” affects human cognition and brain physiology is not well understood. Here the authors show evidence of an association of chronotype with cognitive functions and related physiological parameters.
- Mohammad Ali Salehinejad
- , Miles Wischnewski
- & Michael A. Nitsche