Publications by authors named "Mateo Vélez-Fort"

13 Publications

  • Page 1 of 1

Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1.

Sci Rep 2021 Mar 2;11(1):4983. Epub 2021 Mar 2.

Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, 25 Howland Street, London, W1T 4JG, UK.

Quantitatively comparing brain-wide connectivity of different types of neuron is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine and compare datasets from hierarchical segmentation ontologies, and applied it to long-range presynaptic connectivity onto excitatory and inhibitory neurons, mainly located in layer 2/3 (L2/3), of mouse primary visual cortex (V1). We find that the origins of long-range connections onto these two general cell classes-as well as their proportions-are quite similar, in contrast to the inputs on to a cell type in L6. These anatomical data suggest that distal inputs received by the general excitatory and inhibitory classes of neuron in L2/3 overlap considerably.
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http://dx.doi.org/10.1038/s41598-021-82353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925549PMC
March 2021

A Circuit for Integration of Head- and Visual-Motion Signals in Layer 6 of Mouse Primary Visual Cortex.

Neuron 2018 04 15;98(1):179-191.e6. Epub 2018 Mar 15.

The Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, 25 Howland Street, London W1T 4JG, UK. Electronic address:

To interpret visual-motion events, the underlying computation must involve internal reference to the motion status of the observer's head. We show here that layer 6 (L6) principal neurons in mouse primary visual cortex (V1) receive a diffuse, vestibular-mediated synaptic input that signals the angular velocity of horizontal rotation. Behavioral and theoretical experiments indicate that these inputs, distributed over a network of 100 L6 neurons, provide both a reliable estimate and, therefore, physiological separation of head-velocity signals. During head rotation in the presence of visual stimuli, L6 neurons exhibit postsynaptic responses that approximate the arithmetic sum of the vestibular and visual-motion response. Functional input mapping reveals that these internal motion signals arrive into L6 via a direct projection from the retrosplenial cortex. We therefore propose that visual-motion processing in V1 L6 is multisensory and contextually dependent on the motion status of the animal's head.
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http://dx.doi.org/10.1016/j.neuron.2018.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896233PMC
April 2018

Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex.

Elife 2015 Apr 22;4. Epub 2015 Apr 22.

INSERM U1128, Paris, France.

NG2 cells, oligodendrocyte progenitors, receive a major synaptic input from interneurons in the developing neocortex. It is presumed that these precursors integrate cortical networks where they act as sensors of neuronal activity. We show that NG2 cells of the developing somatosensory cortex form a transient and structured synaptic network with interneurons that follows its own rules of connectivity. Fast-spiking interneurons, highly connected to NG2 cells, target proximal subcellular domains containing GABAA receptors with γ2 subunits. Conversely, non-fast-spiking interneurons, poorly connected with these progenitors, target distal sites lacking this subunit. In the network, interneuron-NG2 cell connectivity maps exhibit a local spatial arrangement reflecting innervation only by the nearest interneurons. This microcircuit architecture shows a connectivity peak at PN10, coinciding with a switch to massive oligodendrocyte differentiation. Hence, GABAergic innervation of NG2 cells is temporally and spatially regulated from the subcellular to the network level in coordination with the onset of oligodendrogenesis.
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http://dx.doi.org/10.7554/eLife.06953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432226PMC
April 2015

The stimulus selectivity and connectivity of layer six principal cells reveals cortical microcircuits underlying visual processing.

Neuron 2014 Sep 28;83(6):1431-43. Epub 2014 Aug 28.

The Division of Neurophysiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address:

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.
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http://dx.doi.org/10.1016/j.neuron.2014.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175007PMC
September 2014

Postnatal down-regulation of the GABAA receptor γ2 subunit in neocortical NG2 cells accompanies synaptic-to-extrasynaptic switch in the GABAergic transmission mode.

Cereb Cortex 2015 Apr 11;25(4):1114-23. Epub 2013 Nov 11.

INSERM U603, Paris, France CNRS UMR 8154, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France and.

NG2 cells, a main pool of glial progenitors, express γ-aminobutyric acid A (GABA(A)) receptors (GABA(A)Rs), the functional and molecular properties of which are largely unknown. We recently reported that transmission between GABAergic interneurons and NG2 cells drastically changes during development of the somatosensory cortex, switching from synaptic to extrasynaptic communication. Since synaptic and extrasynaptic GABA(A)Rs of neurons differ in their subunit composition, we hypothesize that GABA(A)Rs of NG2 cells undergo molecular changes during cortical development accompanying the switch of transmission modes. Single-cell RT-PCR and the effects of zolpidem and α5IA on evoked GABAergic currents reveal the predominance of functional α1- and α5-containing GABA(A)Rs at interneuron-NG2 cell synapses in the second postnatal week, while the α5 expression declines later in development when responses are exclusively extrasynaptic. Importantly, pharmacological and molecular analyses demonstrate that γ2, a subunit contributing to the clustering of GABA(A)Rs at postsynaptic sites in neurons, is down-regulated in NG2 cells in a cell type-specific manner in concomitance with the decline of synaptic activity and the switch of transmission mode. In keeping with the synaptic nature of γ2 in neurons, the down-regulation of this subunit is an important molecular hallmark of the change of transmission modes between interneurons and NG2 cells during development.
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http://dx.doi.org/10.1093/cercor/bht309DOI Listing
April 2015

Oligodendrocyte precursor cells are accurate sensors of local K+ in mature gray matter.

J Neurosci 2013 Feb;33(6):2432-42

INSERM U603, 75006 Paris, France.

Oligodendrocyte precursor cells (OPCs) are the major source of myelinating oligodendrocytes during development. These progenitors are highly abundant at birth and persist in the adult where they are distributed throughout the brain. The large abundance of OPCs after completion of myelination challenges their unique role as progenitors in the healthy adult brain. Here we show that adult OPCs of the barrel cortex sense fine extracellular K(+) increases generated by neuronal activity, a property commonly assigned to differentiated astrocytes rather than to progenitors. Biophysical, pharmacological, and single-cell RT-PCR analyses demonstrate that this ability of OPCs establishes itself progressively through the postnatal upregulation of Kir4.1 K(+) channels. In animals with advanced cortical myelination, extracellular stimulation of layer V axons induces slow K(+) currents in OPCs, which amplitude correlates with presynaptic action potential rate. Moreover, using paired recordings, we demonstrate that the discharge of a single neuron can be detected by nearby adult OPCs, indicating that these cells are strategically located to detect local changes in extracellular K(+) concentration during physiological neuronal activity. These results identify a novel unitary neuron-OPC connection, which transmission does not rely on neurotransmitter release and appears late in development. Beyond their abundance in the mature brain, the postnatal emergence of a physiological response of OPCs to neuronal network activity supports the view that in the adult these cells are not progenitors only.
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http://dx.doi.org/10.1523/JNEUROSCI.1961-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619152PMC
February 2013

Cortical circuits: layer 6 is a gain changer.

Curr Biol 2012 May;22(10):R411-3

The National Institute for Medical Research, The Ridgeway, London, UK.

Stimulation of excitatory cells in layer six of mouse visual cortex results in net inhibition of the spiking of neurons in upper cortical layers; this ascending intra-cortical drive provides a mechanism for gain modulation of sensory-evoked responses.
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http://dx.doi.org/10.1016/j.cub.2012.03.055DOI Listing
May 2012

Central role of GABA in neuron-glia interactions.

Neuroscientist 2012 Jun 23;18(3):237-50. Epub 2011 May 23.

Inserm U603, Paris, France.

The major types of glial cells-astrocytes, microglia, and cells of the oligodendroglial lineage-are known to express functional metabotropic and ionotropic GABA receptors. Neuronal signaling mechanisms allowing for the activation of these receptors in glia are probably as complex as those described among neurons and involve synaptic and extrasynaptic transmission modes. In addition, astrocytes can signal back to neurons by releasing GABA, probably through unconventional nonvesicular mechanisms. The decryption of the roles played by GABAergic signaling in neuron-glia interactions is only beginning, but it has been suggested that activation of glial cells by GABA influences important functions of the brain such as neuronal activity, differentiation, myelination, and neuroprotection. This review discusses the cellular mechanisms allowing the major types of glial cells to sense and transmit GABAergic signals and gives an overview of potential roles of this signaling pathway in developing and mature brains.
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http://dx.doi.org/10.1177/1073858411403317DOI Listing
June 2012

Is neuronal communication with NG2 cells synaptic or extrasynaptic?

J Anat 2011 Jul 24;219(1):8-17. Epub 2011 Feb 24.

Inserm U603 CNRS UMR 8154 Université Paris Descartes, France.

NG2-expressing glial cells (NG2 cells) represent a major pool of progenitors able to generate myelinating oligodendrocytes, and perhaps astrocytes and neurones, in the postnatal brain. In the last decade, it has been demonstrated that NG2 cells receive functional glutamatergic and GABAergic synapses mediating fast synaptic transmission in different brain regions. However, several controversies exist in this field. While two classes of NG2 cells have been defined by the presence or absence of Na(+) channels, action potential firing and neuronal input, other studies suggest that all NG2 cells possess Na(+) conductances and are the target of quantal neuronal release, but are unable to trigger action potential firing. Here we bring new evidence supporting the idea that the level of expression of Na(+) conductances is not a criterion to discriminate NG2 cell subpopulations in the somatosensory cortex. Surprisingly, recent reports demonstrated that NG2 cells detect quantal glutamate release from unmyelinated axons in white matter regions. Yet, it is difficult from these studies to establish whether axonal vesicular release in white matter occurs at genuine synaptic junctions or at ectopic release sites. In addition, we recently reported a new mode of extrasynaptic communication between neurones and NG2 cells that relies on pure GABA spillover and does not require GABAergic synaptic input. This review discusses the properties of quantal neuronal release onto NG2 cells and gives an extended overview of potential extrasynaptic modes of transmission, from ectopic to diffuse volume transmission, between neurones and NG2 cells in the brain.
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http://dx.doi.org/10.1111/j.1469-7580.2011.01350.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130156PMC
July 2011

Postnatal switch from synaptic to extrasynaptic transmission between interneurons and NG2 cells.

J Neurosci 2010 May;30(20):6921-9

Institut National de la Santé et de la Recherche Médicale Unité 603, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8154, Université Paris Descartes, 75006 Paris, France.

NG2 cells, oligodendrocyte precursors, play a critical role in myelination during postnatal brain maturation, but a pool of these precursors is maintained in the adult and recruited to lesions in demyelinating diseases. NG2 cells in immature animals have recently been shown to receive synaptic inputs from neurons, and these have been assumed to persist in the adult. Here, we investigated the GABAergic synaptic activity of NG2 cells in acute slices of the barrel cortex of NG2-DsRed transgenic mice during the first postnatal month, which corresponds to the period of active myelination in the neocortex. Our data demonstrated that the frequency of spontaneous and miniature GABAergic synaptic activity of cortical NG2 cells dramatically decreases after the second postnatal week, indicating a decrease in the number of synaptic inputs onto NG2 cells during development. However, NG2 cells still receive GABAergic inputs from interneurons in the adult cortex. These inputs do not rely on the presence of functional synapses but involve a form of GABA spillover. This GABA volume transmission allows interneurons to induce phasic responses in target NG2 cells through the activation of extrasynaptic GABA(A) receptors. Hence, after development is complete, volume transmission allows NG2 cells to integrate neuronal activity patterns at frequencies occurring during in vivo sensory stimulation.
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http://dx.doi.org/10.1523/JNEUROSCI.0238-10.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632644PMC
May 2010

Holographic photolysis for multiple cell stimulation in mouse hippocampal slices.

PLoS One 2010 Feb 25;5(2):e9431. Epub 2010 Feb 25.

Wavefront-Engineering Microscopy Group, Neurophysiology and New Microscopies Laboratory, CNRS UMR 8154, INSERM U603, University Paris Descartes, Paris, France.

Background: Advanced light microscopy offers sensitive and non-invasive means to image neural activity and to control signaling with photolysable molecules and, recently, light-gated channels. These approaches require precise and yet flexible light excitation patterns. For synchronous stimulation of subsets of cells, they also require large excitation areas with millisecond and micrometric resolution. We have recently developed a new method for such optical control using a phase holographic modulation of optical wave-fronts, which minimizes power loss, enables rapid switching between excitation patterns, and allows a true 3D sculpting of the excitation volumes. In previous studies we have used holographic photololysis to control glutamate uncaging on single neuronal cells. Here, we extend the use of holographic photolysis for the excitation of multiple neurons and of glial cells.

Methods/principal Findings: The system combines a liquid crystal device for holographic patterned photostimulation, high-resolution optical imaging, the HiLo microscopy, to define the stimulated regions and a conventional Ca(2+) imaging system to detect neural activity. By means of electrophysiological recordings and calcium imaging in acute hippocampal slices, we show that the use of excitation patterns precisely tailored to the shape of multiple neuronal somata represents a very efficient way for the simultaneous excitation of a group of neurons. In addition, we demonstrate that fast shaped illumination patterns also induce reliable responses in single glial cells.

Conclusions/significance: We show that the main advantage of holographic illumination is that it allows for an efficient excitation of multiple cells with a spatiotemporal resolution unachievable with other existing approaches. Although this paper focuses on the photoactivation of caged molecules, our approach will surely prove very efficient for other probes, such as light-gated channels, genetically encoded photoactivatable proteins, photoactivatable fluorescent proteins, and voltage-sensitive dyes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009431PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828488PMC
February 2010

Functional alpha 7-containing nicotinic receptors of NG2-expressing cells in the hippocampus.

Glia 2009 Aug;57(10):1104-14

INSERM, U603, Paris, France.

In the postnatal central nervous system, glial cells expressing the chondroitin sulfate proteoglycan NG2 (NG2-cells) constitute a cell population exhibiting several properties of oligodendrocyte precursors such as the ability to proliferate. One particular feature of NG2-cells is that they express several glutamatergic and GABAergic ionotropic receptors activated by synaptic neurotransmitter release. Here, we used patch-clamp recordings, immunostaining, calcium imaging, and intracellular labeling to test for the presence of ionotropic nicotinic acetylcholine receptors (nAChRs) in NG2-cells identified in acute hippocampal slices of mice. We demonstrated that these cells express functional nAChRs during the second postnatal week, i.e., the period in which they become the most abundant proliferative cell type of CA1 stratum radiatum. Pharmacological experiments showed that NG2-cells express alpha 7-containing nAChRs. In particular, the powerful positive allosteric modulator of these receptors PNU-120596 induced a 20-fold increase of agonist-induced currents and revealed rises in intracellular calcium concentration upon agonist applications. In addition, nanomolar concentrations of nicotine, which did not induce any response in these cells, largely desensitized nAChR-mediated currents. These data indicate that the functional expression of Ca(2+)-permeable alpha 7-containing nAChRs in hippocampal slices is not restricted to neurons and that the receptors of NG2-cells can be desensitized by low concentrations of nicotine.
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http://dx.doi.org/10.1002/glia.20834DOI Listing
August 2009