Article
|
Open Access
Featured
-
-
Article
| Open AccessATR regulates neuronal activity by modulating presynaptic firing
Ataxia Telangiectasia and Rad3-related (ATR) is a key regulator of replication stress response; yet, mutations within the ATR gene cause human ATR-Seckel Syndrome associated with microcephaly and intellectual disability. Here, the authors show neuron-specific ATR deletion increases intrinsic neuronal and epileptiform activity, revealing a function of ATR beyond its role in DNA damage response.
- Murat Kirtay
- , Josefine Sell
- & Zhao-Qi Wang
-
Article
| Open AccessNon-invasive, opsin-free mid-infrared modulation activates cortical neurons and accelerates associative learning
Neurostimulant drugs or magnetic/electrical stimulation techniques have shown limited effects on learning capabilities of healthy subjects. The authors show that, without introducing an exogeneous gene, mid-infrared light can modulate firing activity of neurons in vivo and accelerate learning in mice.
- Jianxiong Zhang
- , Yong He
- & Xiaowei Chen
-
Article
| Open AccessBreathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation
Combining optogenetics, behavioral modelling and neural population analysis, the authors show in mice that during fear-related freezing the olfactory bulb transmits 4 Hz breathing rhythm to the prefrontal cortex where this oscillation organizes local activity and regulates freezing episode duration.
- Sophie Bagur
- , Julie M. Lefort
- & Karim Benchenane
-
Article
| Open AccessSpreading depression as an innate antiseizure mechanism
Spreading depression is a prolonged depolarization in the CNS associated with several neurological diseases. Here the authors demonstrate a reciprocal relationship between spreading depression and seizures in an animal model.
- Isra Tamim
- , David Y. Chung
- & Cenk Ayata
-
Article
| Open AccessBi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum
This study presents an anatomical, neurophysiological and functional characterization of four distinct prefrontal populations that project to striatal and thalamic sub-regions. The authors show that each of these populations have a discrete role in the regulation of cognitive control.
- Sybren F. de Kloet
- , Bastiaan Bruinsma
- & Huibert D. Mansvelder
-
Article
| Open AccessHost interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex
Transplantation of embryonic interneurons can restore juvenile plasticity to the adult host visual cortex. Here, the authors show that transplanted embryonic interneurons reactivate cortical plasticity via Neuregulin/ErbB4 signaling in host parvalbumin interneurons.
- XiaoTing Zheng
- , Kirstie J. Salinas
- & Sunil P. Gandhi
-
Article
| Open AccessIn vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons
The in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity. The authors identified biophysical membrane potential signatures associated with distinct in vivo firing patterns in whole-cell recordings of spontaneously active midbrain dopamine neurons.
- Kanako Otomo
- , Jessica Perkins
- & Carlos A. Paladini
-
Article
| Open AccessAstrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle
Several mechanisms contribute to the maintenance of constant extracellular pH, essential for normal brain function. Here the authors show that astrocytes help to control local brain pH via a neuronal activity-dependent release of bicarbonate by the electrogenic sodium bicarbonate cotransporter 1.
- Shefeeq M. Theparambil
- , Patrick S. Hosford
- & Alexander V. Gourine
-
Article
| Open AccessD-serine mitigates cell loss associated with temporal lobe epilepsy
Temporal lobe epilepsy (TLE) can be unresponsive to treatment. Here, the authors show that treatment with D-Serine mitigates TLE and acts on neurons and glia, attenuating neuronal loss and reducing astro- and microgliosis in rodents.
- Stephen Beesley
- , Thomas Sullenberger
- & Sanjay S. Kumar
-
Article
| Open AccessHippocampal hub neurons maintain distinct connectivity throughout their lifetime
In the neonatal hippocampus, GABA cells born the earliest operate as ‘hubs’ by orchestrating population synchrony. Here, the authors show that the earliest born GABAergic cells in the hippocampal CA1 region maintain distinct anatomical and functional properties throughout their lifetime.
- Marco Bocchio
- , Claire Gouny
- & Rosa Cossart
-
Article
| Open AccessDifferential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization
Inhibition in spinal nociceptive pathways is weaker and more labile in lamina I —where thermal input is primarily processed— than in lamina II that encodes predominantly high threshold mechanical input. This explains why noxious thermal input makes spinal circuits prone to catastrophic sensitization.
- Francesco Ferrini
- , Jimena Perez-Sanchez
- & Yves De Koninck
-
Article
| Open AccessAn axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons
The precise subcellular location of ion channels is a key determinant of their functions. Here, subcellular patch-clamp recordings demonstrate that an axon-specific expression of HCN channels facilitates the initiation and propagation of action potentials in parvalbumin-expressing basket cells.
- Fabian C. Roth
- & Hua Hu
-
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
-
Article
| Open AccessEnhancing neuronal chloride extrusion rescues α2/α3 GABAA-mediated analgesia in neuropathic pain
Disinhibition in the dorsal horn of the spinal cord may contribute to chronic pain. Here the authors show that, despite a paradoxical increase in α2/α3 subunits of the GABAA receptor in a neuropathic pain model, inhibition eventually fails due to KCC2 hypofunction.
- Louis-Etienne Lorenzo
- , Antoine G. Godin
- & Yves De Koninck
-
Article
| Open AccessKetamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
The authors show that a subanesthetic dose of ketamine markedly elevate calcium signals in apical dendritic spines in the mouse prefrontal cortex. This effect is driven by a local-circuit mechanism that involves the suppression of somatostatin interneurons leading to dendritic disinhibition.
- Farhan Ali
- , Danielle M. Gerhard
- & Alex C. Kwan
-
Article
| Open AccessIntegrating electric field modeling and neuroimaging to explain inter-individual variability of tACS effects
Electrical stimulation of the brain can have variable effects, perhaps because of individual differences in brain structure which produce differences in the electric fields. Here, the authors show that using functional and structural brain imaging along with electric field modeling can predict the effectiveness of stimulation.
- Florian H. Kasten
- , Katharina Duecker
- & Christoph S. Herrmann
-
Article
| Open AccessTsc1-mTORC1 signaling controls striatal dopamine release and cognitive flexibility
Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 or TSC2 genes, which negatively regulate mTORC1 signalling. Here the authors selectively delete Tsc1 from dopamine neurons in mice and find impairments in striatal dopamine release that are sufficient to reduce cognitive flexibility.
- Polina Kosillo
- , Natalie M. Doig
- & Helen S. Bateup
-
Article
| Open AccessTsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons
Although cortical GABAergic interneuron (CIN) dysfunction is implicated in several neuropsychiatric disorders, we still know very little about how they attain their unique properties or how their dysfunction impacts neuropsychiatric disorders. In this study, authors show that conditional loss of Tsc1, causes SST+ CINs, which are distinct from PV+ CINs, to express PV and adopt fast-spiking properties, via MTOR activity
- Ruchi Malik
- , Emily Ling-Lin Pai
- & Daniel Vogt
-
Article
| Open AccessAltered dendritic spine function and integration in a mouse model of fragile X syndrome
Fragile X syndrome and autism spectrum disorders are associated with circuit hyperexcitability, however, its cellular and synaptic bases are not well understood. Here, the authors report abnormal synaptogenesis with an increased prevalence of polysynaptic spines with normal morphology in a mouse model of fragile X.
- Sam A. Booker
- , Aleksander P. F. Domanski
- & Peter C. Kind
-
Article
| Open AccessCellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex
Somatosensory hypersensitivity in Fmr-1 knockout mice is thought to arise from an increase in cortical circuit excitability. Here, the authors report that the loss of precision of sensory encoding in the Layer 4 of barrel cortex is the primary developmental circuit alteration that drives the other compensatory circuit dysfunction.
- Aleksander P. F. Domanski
- , Sam A. Booker
- & Peter C. Kind
-
Article
| Open AccessMuscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit
Drosophila larvae are able to perform visually-guided behaviours yet the molecular and circuit mechanisms for discriminating changes in light intensity are not known. Here, the authors report that ON versus OFF discrimination results from opposing cholinergic and glutamatergic mechanisms.
- Bo Qin
- , Tim-Henning Humberg
- & Quan Yuan
-
Article
| Open AccessClosed-loop control of gamma oscillations in the amygdala demonstrates their role in spatial memory consolidation
Gamma oscillations have been proposed to underlie many cognitive and memory processes, but it has proven difficult to directly test this by manipulating them. Here, in rats, the authors show that manipulation of gamma oscillations in the amygdala affects memory consolidation.
- Vasiliki Kanta
- , Denis Pare
- & Drew B. Headley
-
Article
| Open AccessSpatial suppression promotes rapid figure-ground segmentation of moving objects
The visual system excels at segregating moving objects from their backgrounds, a key visual function hypothesized to be driven by suppressive centre-surround mechanisms. Here, the authors show that spatial suppression of background motion signals is critical for rapid segmentation of moving objects.
- Duje Tadin
- , Woon Ju Park
- & Randolph Blake
-
Article
| Open AccessModulation of extrasynaptic GABAA alpha 5 receptors in the ventral hippocampus normalizes physiological and behavioral deficits in a circuit specific manner
Region-specific increases in hippocampal activity have been reported in schizophrenia patients, yet there are little known about how these circuit levels changes modulate behavioral deficits. Here authors found that that over-expression of the a5 subunit of the GABAA receptor increased tonic GABA currents and normalized aberrant pyramidal cell activity in the ventral hippocampus which had distinct disease symptom outcomes depending on the pathway targeted
- J. J. Donegan
- , A. M. Boley
- & D. J. Lodge
-
Article
| Open AccessNeural effects of transcranial magnetic stimulation at the single-cell level
Transcranial Magnetic Stimulation (TMS) can modulate human brain activity, but the extent of the cortical area activated by TMS is unclear. Here, the authors show that TMS affects monkey single neuron activity in an area less than 2 mm diameter, while TMS-induced activity and task-related activity do not summate.
- Maria C. Romero
- , Marco Davare
- & Peter Janssen
-
Article
| Open AccessDiverse synaptic and dendritic mechanisms of complex spike burst generation in hippocampal CA3 pyramidal cells
Complex spike burst discharges of hippocampal neurons are proposed to be important for plasticity. Here, the authors report that in CA3 pyramidal neurons complex bursts generated by intrinsic mechanisms, can represent heterogeneous input-output functions and are regulated by HCN and Kv2 channels.
- Snezana Raus Balind
- , Ádám Magó
- & Judit K. Makara
-
Article
| Open AccessAsymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons
In Drosophila antenna, an unusual non-synaptic form of lateral inhibition occurs between subtypes of compartmentalized olfactory receptor neurons (ORNs). Here, authors show that direct electrical (ephaptic) interactions mediate lateral inhibition between ORNs, with physically larger ORNs dominating ephaptic interactions.
- Ye Zhang
- , Tin Ki Tsang
- & Chih-Ying Su
-
Article
| Open AccessAmyloid β oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate
The underlying mechanism of amyloid β (Aβ) oligomer-induced aberrant neurotransmitter release remains unclear. Here, authors show that the release probability at the synapse between the Schaffer collateral and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production and is mainly due to an mGluR5-mediated depletion of PIP2 in axons.
- Yang He
- , Mengdi Wei
- & Yu-Dong Zhou
-
Article
| Open AccessCorrespondence between cerebral glucose metabolism and BOLD reveals relative power and cost in human brain
The brain primarily uses glucose to generate energy, but the relationship of neuronal activity to glucose utilization is not necessarily a simple linear one. Here, the authors introduce relative power (rPWR) and relative cost (rCST) as new metrics to quantify how brain activity relates to glucose consumption.
- Ehsan Shokri-Kojori
- , Dardo Tomasi
- & Nora D. Volkow
-
Article
| Open AccessIgSF9b regulates anxiety behaviors through effects on centromedial amygdala inhibitory synapses
IgSF9b is a synaptic adhesion protein that has been linked to psychiatric disorders. Here the authors show that deletion of IgSF9b regulates anxiety-like behaviour in mice by increasing inhibitory synaptic transmission in the centromedial amygdala.
- Olga Babaev
- , Hugo Cruces-Solis
- & Dilja Krueger-Burg
-
Article
| Open AccessAutapses enhance bursting and coincidence detection in neocortical pyramidal cells
While autapses are synapses made by a neuron onto itself, its functional significance in pyramidal cells are not clear. Here, the authors show that in the mammalian neocortex, autapses of pyramidal cells can enhance burst firing and coincidence detection from other inputs.
- Luping Yin
- , Rui Zheng
- & Yousheng Shu
-
Article
| Open AccessPerineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy
Brain tumours are associated with epilepsy. Here the authors show, using a mouse model, that the degradation of perineuronal nets around fast spiking interneurons near the tumour contribute to seizures by increasing their membrane capacitance and firing.
- Bhanu P. Tewari
- , Lata Chaunsali
- & Harald Sontheimer
-
Article
| Open AccessSleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients
Many brain-injured patients retain large cortical islands that are intact, active and reactive but blocked in a state of low complexity, leading to unconsciousness. Here, the authors show that this loss of complexity is due to the pathological engagement of sleep-like neuronal mechanisms.
- M. Rosanova
- , M. Fecchio
- & M. Massimini
-
Article
| Open AccessA microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers
Peripheral nerves have a complex physiology and it is therefore difficult to measure axonal activity in vitro. Here the authors make a nerve-on-a-chip platform to align peripheral nerves and permit measurement of conduction amplitude and velocity along several axons in a single experiment.
- Sandra Gribi
- , Sophie du Bois de Dunilac
- & Stéphanie P. Lacour
-
Article
| Open AccessHigh-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins
Current optogenetic inhibition methods like light-controlled ion pumps require high-intensity light and disrupt physiological ion gradients. Here, the authors somatically target the anion-conducting opsin GtACR to eliminate spiking in distal axons and improve photocurrents, thus enhancing its utility.
- Mathias Mahn
- , Lihi Gibor
- & Ofer Yizhar
-
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
-
Article
| Open AccessRegion-specific and state-dependent action of striatal GABAergic interneurons
Striatal GABAergic interneurons regulate the influence of cortical inputs on striatal projection neurons through feedforward inhibition. Here, the authors report that this inhibition is mediated mainly by PV interneurons in the dorsolateral striatum and SOM interneurons in the dorsomedial striatum.
- Elodie Fino
- , Marie Vandecasteele
- & Laurent Venance
-
Article
| Open AccessMicroglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum
In the mammalian cerebellum, surplus synapses between climbing fibers (CF) and Purkinje cells (PC) are developmentally pruned. Here, Nakayama and colleagues show that ablation of microglia impairs pruning of CF-PC synapses because of dysfunction of GABAergic inhibition prerequisite for pruning.
- Hisako Nakayama
- , Manabu Abe
- & Kouichi Hashimoto
-
Article
| Open AccessThe interdependence of excitation and inhibition for the control of dynamic breathing rhythms
Excitatory neurons in the preBötzinger Complex generate bursting activity responsible for breathing, but these alone cannot generate physiological breathing frequencies. Here the authors show how inhibition regulates refractory properties of excitatory neurons to allow dynamic breathing rhythms.
- Nathan Andrew Baertsch
- , Hans Christopher Baertsch
- & Jan Marino Ramirez
-
Article
| Open AccessFluid network dynamics in the prefrontal cortex during multiple strategy switching
Population activity of neurons in the prefrontal cortex has been shown to represent cognitive strategy and rules. Here the authors report that when the same rule is repeated on multiple occasions in the task, it is accompanied each time by a new prefrontal firing rate state.
- Hugo Malagon-Vina
- , Stephane Ciocchi
- & Thomas Klausberger
-
Article
| Open AccessInterneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes
Interneurons in the neocortex have functional and morphological subtypes. Here, Mariotti and colleagues show that activation of parvalbumin-expressing interneurons evokes depressing calcium responses in astrocytes while somatostatin-expressing interneurons evoke potentiating astrocytic responses.
- Letizia Mariotti
- , Gabriele Losi
- & Giorgio Carmignoto
-
Article
| Open AccessMidbrain circuit regulation of individual alcohol drinking behaviors in mice
Mice exposed to a two-bottle alcohol choice paradigm can be divided into high and low drinking groups. Here, the authors show that stimulating VTA neurons to induce higher phasic activity patterns that are observed in low alcohol drinking mice, suppresses alcohol drinking in mice that are high alcohol drinking.
- Barbara Juarez
- , Carole Morel
- & Ming-Hu Han
-
Correspondence
| Open AccessCorrespondence: Reply to ‘Revisiting the theoretical cell membrane thermal capacitance response’
- Mikhail G. Shapiro
- , Kazuaki Homma
- & Francisco Bezanilla
-
Article
| Open AccessSpatiotemporal dynamics of information encoding revealed in orbitofrontal high-gamma
High gamma activity (HGA) and local neurons encode similar information, but it’s unclear if this is true when neurons are heterogeneous, as in the orbitofrontal cortex (OFC). Here, Rich & Wallis show that HGA in OFC is closely related to neuron firing, but reveals clearer spatiotemporal dynamics.
- Erin L. Rich
- & Joni D. Wallis
-
Article
| Open AccessAfferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells
Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.
- R. Chittajallu
- , J. C. Wester
- & C. J. McBain
-
Article
| Open AccessEndogenous opioids regulate moment-to-moment neuronal communication and excitability
The endogenous opioid system regulates fear and anxiety, but the underlying cellular mechanism is unclear. Winterset al. shows that in the intercalated cells (ITC) of the amygdala, endogenous opioids suppress glutamatergic inputs via the δ-opioid receptor presynaptically, and reduce the excitability of ITCs via the μ-opioid receptor postsynaptically.
- Bryony L. Winters
- , Gabrielle C. Gregoriou
- & Elena E. Bagley
-
Article
| Open AccessTheory of optimal balance predicts and explains the amplitude and decay time of synaptic inhibition
Inhibition and excitation are counterbalanced at synapses, but the conditions that constitute optimal balance are not known. Here the authors show through modelling that the properties of synaptic inhibition are fine-tuned to maintain an optimal balance in which peak excitation reaches precisely to spike threshold.
- Jaekyung K. Kim
- & Christopher D. Fiorillo
-
Article
| Open AccessDopaminergic dynamics underlying sex-specific cocaine reward
Sex differences in reward processing are at present poorly understood. Calipari and Juarezet al. report oestrous cycle-dependent fluctuations in firing of VTA dopamine neurons that drive alterations in DAT function expressed in terminals in the NAc. These differences underlie enhanced cocaine reward processing during oestrus.
- Erin S. Calipari
- , Barbara Juarez
- & Eric J Nestler
-
Article
| Open AccessThe Ca2+-activated chloride channel anoctamin-2 mediates spike-frequency adaptation and regulates sensory transmission in thalamocortical neurons
Spike-frequency adaptation in thalamocortical (TC) neurons is important for sensory transmission though the underlying mechanisms are not fully understood. Here, the authors identify a role for the calcium-activated chloride channel, ANO2, in mediating TC spiking adaptations and visceral pain response.
- Go Eun Ha
- , Jaekwang Lee
- & Eunji Cheong