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| Open AccessRetromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis
ALS is a neurodegenerative disease characterized by loss of motor neurons. Here, the authors showed that reduced levels of the VSP35 subunit in the retromer complex is a conserved ALS feature and identified a new lead compound increasing retromer stability ameliorating the disease phenotype.
- Luca Muzio
- , Riccardo Sirtori
- & Gianvito Martino
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Article
| Open AccessUnexpected complexity of everyday manual behaviors
How does the brain control the complex movements of hands? Here, by tracking human hand kinematics and applying multidimensional reduction techniques, the authors provide evidence that grasping involves a complex control system that regulates even the most subtle aspects of hand movement.
- Yuke Yan
- , James M. Goodman
- & Sliman J. Bensmaia
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Article
| Open AccessDifferential contributions of the two cerebral hemispheres to temporal and spectral speech feedback control
Speech production is thought to rely on speech motor programs in the left cerebral hemisphere and on auditory feedback control by the right halve of the human brain. Here, the authors reveal that the left hemisphere preferentially controls temporal speech features while the right hemisphere controls speech by analyzing spectral features of the auditory feedback.
- Mareike Floegel
- , Susanne Fuchs
- & Christian A. Kell
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Article
| Open AccessDeep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
Deep brain stimulation (DBS) is a symptomatic treatment of Parkinson’s disease (PD) that benefits only a minority of patients. Here, the authors show that activation of cortical somatostatin interneurons alleviates motor symptoms in a mouse model of PD and may constitute a less invasive alternative than DBS.
- Sébastien Valverde
- , Marie Vandecasteele
- & Laurent Venance
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Article
| Open AccessExercise enhances motor skill learning by neurotransmitter switching in the adult midbrain
Exercise promotes motor skill learning via unclear mechanisms. Here, the authors show that running wheel training results in neurotransmitter switching in caudal pedunculopontine nucleus neurons of mice. These neurons project to several brain regions, regulating the acquisition of motor skills.
- Hui-quan Li
- & Nicholas C. Spitzer
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Article
| Open AccessFunctional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum
Striatal dopaminoceptive neurons are molecularly and functionally heterogeneous. Here, the authors provide the translatome of D2R striatal neurons and identified hundreds of region specific molecular markers as well as testing their resource to shed light into function.
- Emma Puighermanal
- , Laia Castell
- & Emmanuel Valjent
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Article
| Open AccessOptogenetic manipulation of a value-coding pathway from the primate caudate tail facilitates saccadic gaze shift
The caudate tail encodes the stable value associated with visual objects and modulates gaze accordingly. Here, the authors use pathway-specific optogenetic manipulation of the caudate terminals in the substantia nigra pars reticulata on oculomotor behaviour.
- Hidetoshi Amita
- , Hyoung F. Kim
- & Okihide Hikosaka
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Article
| Open AccessCholinergic midbrain afferents modulate striatal circuits and shape encoding of action strategies
Acetylcholine (ACh) in the striatum is involved in mediating action flexibility. Here the authors show that midbrain cholinergic nuclei provide a new source of Ach in the striatum, form excitatory synapses with striatal cholinergic interneurons (CIN) and contribute to instrumental learning.
- Daniel Dautan
- , Icnelia Huerta-Ocampo
- & Juan Mena-Segovia
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Article
| Open AccessFemale copulation song is modulated by seminal fluid
Male fruitflies sing a patterned wing song during courtship. Here, the authors show that females sing a distinct song during copulation, which is controlled by sex-specific neurons, depends on seminal fluid from the male accessory gland and modulates latency of female remating with subsequent males.
- Peter Kerwin
- , Jiasheng Yuan
- & Anne C. von Philipsborn
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Article
| Open AccessIntrinsic neuronal properties represent song and error in zebra finch vocal learning
The regulation of cellular neuronal properties distinct from synaptic plasticity has been proposed as a mechanism of functional network organization. Here, the authors show that the magnitude of five ion currents in basal ganglia projection song system forebrain neurons covary across life, rapidly and dynamically relating to learned features of individual zebra finches’ songs.
- Arij Daou
- & Daniel Margoliash
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Article
| Open AccessDirect electrical stimulation of the premotor cortex shuts down awareness of voluntary actions
Here, using electrical stimulation on patients undergoing awake brain surgery, the authors show that disruption of the premotor cortex makes patients unconscious of motor arrest. This finding suggests the premotor cortex is crucial for motor awareness.
- Luca Fornia
- , Guglielmo Puglisi
- & Francesca Garbarini
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Article
| Open AccessControl of locomotor speed, arousal, and hippocampal theta rhythms by the nucleus incertus
In addition to activation of locomotor circuits, navigation also requires regulation of arousal and spatial memory processes. Here the authors identify neuromedin B neurons in the nucleus incertus and their subcortical projections in controlling these various processes during navigation.
- Lihui Lu
- , Yuqi Ren
- & Minmin Luo
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Article
| Open AccessInhibition within a premotor circuit controls the timing of vocal turn-taking in zebra finches
Control over when to initiate or withhold vocalizations is essential for vocal turn-taking. Here the authors investigate vocal interactions in zebra finches and show that inhibition within the premotor nucleus HVC plays an important role in the precise timing of vocal motor responses.
- Jonathan I. Benichov
- & Daniela Vallentin
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Article
| Open AccessEnhancing plasticity in central networks improves motor and sensory recovery after nerve damage
Peripheral nerve damage generates maladaptive neuroplasticity as central networks attempt to compensate for the loss of peripheral connectivity. Here, the authors reverse the aberrant plasticity via vagus nerve stimulation to elicit synaptic reorganization and to improve sensorimotor recovery.
- Eric C. Meyers
- , Nimit Kasliwal
- & Seth A. Hays
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Article
| Open AccessComparative analysis of squamate brains unveils multi-level variation in cerebellar architecture associated with locomotor specialization
The cerebellum is critical in sensory-motor control and is structurally diverse across vertebrates. Here, the authors investigate the evolutionary relationship between locomotory mode and cerebellum architecture across squamates by integrating study of gene expression, cell distribution, and 3D morphology.
- Simone Macrì
- , Yoland Savriama
- & Nicolas Di-Poï
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Perspective
| Open AccessHierarchical motor control in mammals and machines
Recent research in motor neuroscience has focused on optimal feedback control of single, simple tasks while robotics and AI are making progress towards flexible movement control in complex environments employing hierarchical control strategies. Here, the authors argue for a return to hierarchical models of motor control in neuroscience.
- Josh Merel
- , Matthew Botvinick
- & Greg Wayne
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Article
| Open AccessContext-dependent limb movement encoding in neuronal populations of motor cortex
Network activity in primary motor cortex (M1) controls dexterous limb movements. Here, the authors show that the M1 population code varies according to contextual motor demands that are conveyed via the secondary motor cortex (M2).
- Wolfgang Omlor
- , Anna-Sophia Wahl
- & Fritjof Helmchen
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Article
| Open AccessHierarchical control of locomotion by distinct types of spinal V2a interneurons in zebrafish
V2a excitatory interneurons in the spinal cord are important for coordinating locomotion. Here the authors describe two types of V2a neuron with differences in higher order and lower order connectivity in larval zebrafish.
- Evdokia Menelaou
- & David L. McLean
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Article
| Open AccessSensory representations in the striatum provide a temporal reference for learning and executing motor habits
The authors combine anatomical mapping, electrophysiological recordings, lesions, and pharmacological and optogenetic manipulations in rats to examine the role of forelimb somatosensory flow in the dorsolateral striatum in the learning and execution of motor habits.
- Ana E. Hidalgo-Balbuena
- , Annie Y. Luma
- & Pavel E. Rueda-Orozco
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Article
| Open AccessCognitive control of complex motor behavior in marmoset monkeys
Whether marmosets can exhibit complex motor tasks in controlled experimental designs has not yet been demonstrated. Here, the authors show that marmoset monkeys can be trained to call on command in controlled operant conditioning tasks.
- Thomas Pomberger
- , Cristina Risueno-Segovia
- & Steffen R. Hage
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Article
| Open AccessInformation-based centralization of locomotion in animals and robots
Model-based centralization schemes, though able to quantify locomotion control in animals and bio-inspired robots, are limited to specific systems. Here, the authors report a generalized information-based centralization scheme that unifies existing models and can be applied to different systems.
- Izaak D. Neveln
- , Amoolya Tirumalai
- & Simon Sponberg
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Article
| Open AccessBrainstem and spinal cord MRI identifies altered sensorimotor pathways post-stroke
There are few studies of structural changes in ascending and descending sensorimotor pathways after stroke, beyond the corticospinal tract, in the brain. Here the authors identify changes in white matter structure in brainstem and spinal cord following stroke, and show its relationship to motor impairment.
- Haleh Karbasforoushan
- , Julien Cohen-Adad
- & Julius P. A. Dewald
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Article
| Open AccessReal-time decoding of question-and-answer speech dialogue using human cortical activity
Speech neuroprosthetic devices should be capable of restoring a patient’s ability to participate in interactive dialogue. Here, the authors demonstrate that the context of a verbal exchange can be used to enhance neural decoder performance in real time.
- David A. Moses
- , Matthew K. Leonard
- & Edward F. Chang
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Article
| Open AccessDecoupling of timescales reveals sparse convergent CPG network in the adult spinal cord
Spinal CPGs transmit movement commands through rhythmic synaptic drive onto the spinal premotor network. Here, the authors use paired recordings to demonstrate that spinal neurons have decorrelated synaptic activity suggesting a CPG network with sparse convergent connectivity.
- Marija Radosevic
- , Alex Willumsen
- & Rune W. Berg
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Article
| Open AccessSimultaneous motor preparation and execution in a last-moment reach correction task
Motor preparation processes guide movement. Here, by recording neural activity in monkeys reaching toward targets that can change location, the authors provide evidence that changing a prepared movement midway through completion reengages motor preparation.
- K. Cora Ames
- , Stephen I. Ryu
- & Krishna V. Shenoy
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Article
| Open AccessA striatal interneuron circuit for continuous target pursuit
Many natural behaviours involve tracking of a target in space. Here, the authors describe a task to assess this behaviour in mice and use in vivo electrophysiology, calcium imaging, optogenetics, and chemogenetics to investigate the role of the striatum in target pursuit.
- Namsoo Kim
- , Haofang E. Li
- & Henry H. Yin
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Article
| Open AccessDuets recorded in the wild reveal that interindividually coordinated motor control enables cooperative behavior
Recording neural activity during coordinated behaviors in controlled environments limits opportunities for understanding natural interactions. Here, the authors record from freely moving duetting birds in their natural habitats to reveal the neural mechanisms of interindividual motor coordination.
- Susanne Hoffmann
- , Lisa Trost
- & Manfred Gahr
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Article
| Open AccessIn vivo nuclear capture and molecular profiling identifies Gmeb1 as a transcriptional regulator essential for dopamine neuron function
Despite the known role of midbrain dopaminergic (mDA) signaling in the homeostatic control of mood and motor functions, little is known about how gene expression in these neurons is regulated. Here, authors develop an in vivo nuclear tagging and capture technique for low-input chromatin accessibility and transcriptome profiling of genetically-defined neuron populations to identify Gmeb1 as a novel transcriptional regulator of mDA neurons, whose loss of function impairs motor control in mice.
- Luis M. Tuesta
- , Mohamed N. Djekidel
- & Yi Zhang
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Article
| Open AccessAugmented manipulation ability in humans with six-fingered hands
Can the human brain successfully control additional body parts beyond the ones we normally possess? Here, the authors study two polydactyly individuals (with an additional finger on each hand) and show that they can carry out more complex movements, performing with only one hand tasks normally requiring two.
- C. Mehring
- , M. Akselrod
- & E. Burdet
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Article
| Open AccessRegulation of locomotor speed and selection of active sets of neurons by V1 neurons
During evoked swims, zebrafish larvae transition from fast to slow speeds. Here, the authors elucidate the circuit mechanisms in the central pattern generators in the spinal cord and show that genetically labeled V1 spinal interneurons provide in phase inhibition onto fast and slow motor neurons that are involved in the switching behaviour.
- Yukiko Kimura
- & Shin-ichi Higashijima
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Article
| Open AccessImpaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation
It is known that Purkinje cell PKC-dependent depression is involved in the stabilization of self-motion based hippocampal representation. Here the authors describe decreased stability of hippocampal place cells based on allocentric cues in mice lacking Purkinje cell PP2B-dependent potentiation.
- Julie Marie Lefort
- , Jean Vincent
- & Christelle Rochefort
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Article
| Open AccessExcitatory rubral cells encode the acquisition of novel complex motor tasks
The red nucleus (RN) is a midbrain nucleus known to be involved in the fine control of limb movements, but its role in motor learning is unclear. Here, the authors identified a neuronal population within the red nucleus, co-expressing Vglut2, PV and C1Ql2, which undergoes training-dependent plasticity.
- Giorgio Rizzi
- , Mustafa Coban
- & Kelly R. Tan
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Article
| Open AccessIdentification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies
The wiring of peripheral neural circuits that regulate heart rate is poorly understood. In this study, authors used tissue clearing for high-resolution characterization of nerves in the heart in 3D and transgenic and novel viral vector approaches to identify peripheral parasympathetic and sympathetic neuronal populations involved in heart rate control in mice.
- Pradeep S. Rajendran
- , Rosemary C. Challis
- & Kalyanam Shivkumar
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Article
| Open AccessMacaque dorsal premotor cortex exhibits decision-related activity only when specific stimulus–response associations are known
It is not clear to what degree activity in dorsal premotor cortex (PMd) reflects perceptual-deliberation versus action-selection aspects of decision-making. Here, the authors report that monkey PMd neurons do not express correlates of the perceptual decision independently of the action choices.
- Megan Wang
- , Christéva Montanède
- & John F. Kalaska
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Article
| Open AccessStrong neuron-to-body coupling implies weak neuron-to-neuron coupling in motor cortex
Some cortical neurons fire together like a synchronized chorus, while others fire independently like soloists. Here, the authors show that soloist neurons in motor cortex tend to control body movements, while the choristers do not, and that soloists can become choristers by increasing inhibition.
- Patrick A. Kells
- , Shree Hari Gautam
- & Woodrow L. Shew
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Article
| Open AccessIntrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology
Resting-state fMRI shows networks of correlated activity in the spinal cord, similar to those in the brain, but whether fMRI is a valid measure of functional connectivity in spinal cord is unclear. Here, the authors show that fMRI corresponds well to electrophysiological measures of spinal cord activity.
- Tung-Lin Wu
- , Pai-Feng Yang
- & John C. Gore
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Article
| Open AccesstACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves
Transcranial alternating current stimulation (tACS) uses weak electrical currents, applied to the head, to modulate brain activity. Here, the authors show that contrary to previous assumptions, the effects of tACS on the brain may be mediated by its effect on peripheral nerves in the skin, not direct.
- Boateng Asamoah
- , Ahmad Khatoun
- & Myles Mc Laughlin
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Article
| Open AccessAn orderly single-trial organization of population dynamics in premotor cortex predicts behavioral variability
To explain the neural correlates of behavior and its variability, one must analyze single-trial population dynamics. Here, the authors develop a statistical method that extracts low-dimensional dynamics that explain behavior better than high-dimensional neural activity revealing unexpected structure.
- Ziqiang Wei
- , Hidehiko Inagaki
- & Shaul Druckmann
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Article
| Open AccessDissociable cognitive strategies for sensorimotor learning
Motor learning is thought to be mostly procedural, but recent work has suggested that there is a strong cognitive component to it. Here, the authors show that humans use dissociable cognitive strategies, either caching successful responses or using a rule-based strategy, to solve a visuomotor learning task.
- Samuel D. McDougle
- & Jordan A. Taylor
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Article
| Open AccessRapid and robust restoration of breathing long after spinal cord injury
Respiratory failure is one of the leading causes of death following spinal cord injury and it is unclear if normal respiratory motor activity can be recovered after chronic injury-induced paralysis. Here, authors show that treatment with chondroitinase ABC induces robust rescue of breathing up to 1.5 years following complete hemidiaphragm paralysis.
- Philippa M. Warren
- , Stephanie C. Steiger
- & Jerry Silver
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Article
| Open AccessImaging neural activity in the ventral nerve cord of behaving adult Drosophila
The Drosophila ventral nerve cord (VNC) is functionally equivalent to the vertebrate spinal cord. This study reports a 2-photon imaging approach for recording neural activity in the VNC of walking and grooming adult flies.
- Chin-Lin Chen
- , Laura Hermans
- & Pavan Ramdya
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Article
| Open AccessCortical population activity within a preserved neural manifold underlies multiple motor behaviors
Motor cortical neurons enable performance of a wide range of movements. Here, the authors report that dominant population activity patterns, the neural modes, are largely preserved across various tasks, with many displaying consistent temporal dynamics and reliably mapping onto muscle activity.
- Juan A. Gallego
- , Matthew G. Perich
- & Lee E. Miller
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Article
| Open AccessTopographic precision in sensory and motor corticostriatal projections varies across cell type and cortical area
How corticostriatal connections of different pyramidal cell types are organized, particularly in convergent circuits, has not been evaluated in detail. Here, cell type-specific Cre-driver mice reveal that pyramidal tract-type corticostriatal projections, though broadly similar to intratelencephalic-type projections from the same cortical region, are generally more restricted and variable in their topographic termination patterns.
- Bryan M. Hooks
- , Andrew E. Papale
- & Charles R. Gerfen
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Article
| Open AccessSuper-wide-field two-photon imaging with a micro-optical device moving in post-objective space
Recording the activity of neurons over large brain regions requires expanding the field of view of the optics without losing on spatial and temporal resolution. Here, the authors report a micro-opto-mechanical device that enables two-photon imaging across distant motor areas around 6 mm apart in the mouse.
- Shin-Ichiro Terada
- , Kenta Kobayashi
- & Masanori Matsuzaki
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Article
| Open AccessSingle reach plans in dorsal premotor cortex during a two-target task
It is debated whether motor cortical activity reflects plans for multiple potential actions. Here, the authors report that in a delayed response task with two potential reach targets, population activity in the dorsal premotor cortex at any moment in time represents only one of the targets.
- Brian M. Dekleva
- , Konrad P. Kording
- & Lee E. Miller
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Article
| Open AccessSimultaneous dendritic voltage and calcium imaging and somatic recording from Purkinje neurons in awake mice
Dendritic integration is important for information processing in the brain. Here, in awake mice, authors combine simultaneous dendritic recording of voltage and calcium signals, with somatic recording from Purkinje neurons, enabling characterization of dendritic spiking, action potential backpropagation, and ‘hotspots’ in spiny dendrites.
- Christopher J. Roome
- & Bernd Kuhn
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Article
| Open AccessV2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements
Locomotor circuits in the spinal cord produce precise movements with variations in timing and vigor. Here, the authors report that such motor flexibility is generated through the specificity of connections between subtypes of V2a interneurons and motoneuron populations and their distinct plasticity mechanisms.
- Jianren Song
- , Elin Dahlberg
- & Abdeljabbar El Manira
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Article
| Open AccessSmooth tracking of visual targets distinguishes lucid REM sleep dreaming and waking perception from imagination
When tracking a moving object, our eyes make smooth pursuit movements; however, tracking an imaginary object produces jerky saccadic eye movements. Here, the authors show that during lucid dreams, the eyes smoothly follow dreamed objects. In this respect, dream imagery is more similar to perception than imagination.
- Stephen LaBerge
- , Benjamin Baird
- & Philip G. Zimbardo
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Article
| Open AccessNeonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction
Premature infants are vulnerable to hypoxia and thus white matter injury, especially in the cerebellum, which develops during late gestation. Here, the authors test the effects of perinatal hypoxia on motor performance and rescue behavioral deficits using the GABA reuptake inhibitor Tiagabine.
- Aaron Sathyanesan
- , Srikanya Kundu
- & Vittorio Gallo