Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Nature ; 501(7468): 543-6, 2013 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-23975100

RESUMEN

Early sensory experience instructs the maturation of neural circuitry in the cortex. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.


Asunto(s)
Período Crítico Psicológico , Predominio Ocular/fisiología , Inhibición Neural , Plasticidad Neuronal/fisiología , Visión Monocular/fisiología , Corteza Visual/fisiología , Animales , Predominio Ocular/efectos de los fármacos , Femenino , Interneuronas/citología , Interneuronas/efectos de los fármacos , Rayos Láser , Masculino , Ratones , Inhibición Neural/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Parvalbúminas/metabolismo , Estimulación Luminosa , Privación Sensorial/fisiología , Visión Binocular/efectos de los fármacos , Visión Binocular/fisiología , Visión Monocular/efectos de los fármacos , Corteza Visual/citología , Corteza Visual/efectos de los fármacos
2.
J Neurosci ; 36(43): 11006-11012, 2016 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-27798181

RESUMEN

A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the "critical period," when the circuitry of primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal nogo-66-receptor 1 (ngr1/rtn4r) is required to close the critical period. Here we combined mouse genetics, electrophysiology, and circuit mapping with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1 We demonstrate that ngr1 mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a "lower PV network configuration" in both critical-period wild-type mice and adult ngr1-/- mice. We propose that ngr1 limits disinhibition to close the critical period for OD plasticity and that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons. SIGNIFICANCE STATEMENT: Life experience refines brain circuits throughout development during specified critical periods. Abnormal experience during these critical periods can yield enduring maladaptive changes in neural circuits that impair brain function. In the developing visual system, visual deprivation early in life can result in amblyopia (lazy-eye), a prevalent childhood disorder comprising permanent deficits in spatial vision. Here we identify that the nogo-66 receptor 1 gene restricts an early and essential step in OD plasticity to the critical period. These findings link the emerging circuit-level description of OD plasticity to the genetic regulation of the critical period. Understanding how plasticity is confined to critical periods may provide clues how to better treat amblyopia.


Asunto(s)
Período Crítico Psicológico , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Receptor Nogo 1/metabolismo , Corteza Visual/fisiología , Percepción Visual/fisiología , Adaptación Fisiológica/fisiología , Envejecimiento/metabolismo , Animales , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Nogo 1/genética
3.
J Physiol ; 594(7): 1891-910, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26844927

RESUMEN

KEY POINTS: Using functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory neurons in layers 2/3-6 of the mouse visual cortex (V1). Laminar-specific synaptic wiring diagrams of excitatory neurons were constructed on the basis of circuit mapping. The present study reveals that that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks in V1. ABSTRACT: In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3-6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer-specific organization of excitatory inputs. Remarkably, the spatial extent of inhibitory inputs of excitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex.


Asunto(s)
Potenciales Postsinápticos Excitadores , Potenciales Postsinápticos Inhibidores , Corteza Visual/fisiología , Animales , Conectoma , Femenino , Ácido Glutámico/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/fisiología , Sinapsis/metabolismo , Sinapsis/fisiología , Corteza Visual/citología
4.
J Neurophysiol ; 115(6): 3204-16, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27052587

RESUMEN

The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types.


Asunto(s)
Mapeo Encefálico , Neuronas/fisiología , Núcleos Septales/citología , Potenciales Sinápticos/fisiología , Animales , Channelrhodopsins , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Ácido Glutámico/farmacología , Técnicas In Vitro , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Ratones Transgénicos , Microscopía Confocal , Neuronas/efectos de los fármacos , Optogenética , Técnicas de Placa-Clamp , Somatostatina/genética , Somatostatina/metabolismo , Potenciales Sinápticos/efectos de los fármacos
5.
J Physiol ; 592(10): 2183-96, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24639485

RESUMEN

Melanin-concentrating hormone (MCH)-producing neurons are known to regulate a wide variety of physiological functions such as feeding, metabolism, anxiety and depression, and reward. Recent studies have revealed that MCH neurons receive projections from several wake-promoting brain regions and are integral to the regulation of rapid eye movement (REM) sleep. Here, we provide evidence in both rats and mice that MCH neurons express histamine-3 receptors (H3R), but not histamine-1 (H1R) or histamine-2 (H2R) receptors. Electrophysiological recordings in brain slices from a novel line of transgenic mice that specifically express the reporter ZsGreen in MCH neurons show that histamine strongly inhibits MCH neurons, an effect which is TTX insensitive, and blocked by the intracellular presence of GDP-ß-S. A specific H3R agonist, α-methylhistamine, mimicks the inhibitory effects of histamine, and a specific neutral H3R antagonist, VUF 5681, blocks this effect. Tertiapin Q (TPQ), a G protein-dependent inwardly rectifying potassium (GIRK) channel inhibitor, abolishes histaminergic inhibition of MCH neurons. These results indicate that histamine directly inhibits MCH neurons through H3R by activating GIRK channels and suggest that that inhibition of the MCH system by wake-active histaminergic neurons may be responsible for silencing MCH neurons during wakefulness and thus may be directly involved in the regulation of sleep and arousal.


Asunto(s)
Histamina/farmacología , Hormonas Hipotalámicas/metabolismo , Melaninas/metabolismo , Neuronas/fisiología , Hormonas Hipofisarias/metabolismo , Receptores Histamínicos H3/metabolismo , Sueño/fisiología , Vigilia/fisiología , Animales , Células Cultivadas , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Antagonistas de los Receptores Histamínicos H3/farmacología , Masculino , Ratones , Ratones Transgénicos , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos
6.
Hum Vaccin Immunother ; 18(6): 2100189, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36018753

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Factor Estimulante de Colonias de Granulocitos y Macrófagos , SARS-CoV-2 , Sistemas de Atención de Punto , Glicoproteína de la Espiga del Coronavirus , Inmunidad Celular , Células Dendríticas , Anticuerpos Antivirales
7.
J Neurophysiol ; 103(4): 2301-12, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20130040

RESUMEN

The development of modern neuroscience tools is critical for deciphering brain circuit organization and function. An important aspect for technical development is to enhance each technique's advantages and compensate for limitations. We developed a high-precision and fast functional mapping technique in brain slices that incorporates the spatial precision of activation that can be achieved by laser-scanning photostimulation with rapid and high-temporal resolution assessment of evoked network activity that can be achieved by voltage-sensitive dye imaging. Unlike combination of whole cell recordings with photostimulation for mapping local circuit inputs to individually recorded neurons, this innovation is a new photostimulation-based technique to map cortical circuit output and functional connections at the level of neuronal populations. Here we report on this novel technique in detail and show its effective applications in mapping functional connections and circuit dynamics in mouse primary visual cortex and hippocampus. Given that this innovation enables rapid mapping and precise evaluation of cortical organization and function, it can have broad impacts in the field of cortical circuitry.


Asunto(s)
Mapeo Encefálico/métodos , Rayos Láser , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Imagen de Colorante Sensible al Voltaje/métodos , Animales , Fenómenos Electrofisiológicos/fisiología , Hipocampo/fisiología , Ratones , Ratones Endogámicos C57BL , Modelos Animales
8.
Curr Biol ; 30(15): 2962-2973.e5, 2020 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-32589913

RESUMEN

Disrupting binocular vision during a developmental critical period can yield enduring changes to ocular dominance (OD) in primary visual cortex (V1). Here we investigated how this experience-dependent plasticity is coordinated within the laminar circuitry of V1 by deleting separately in each cortical layer (L) a gene required to close the critical period, nogo-66 receptor (ngr1). Deleting ngr1 in excitatory neurons in L4, but not in L2/3, L5, or L6, prevented closure of the critical period, and adult mice remained sensitive to brief monocular deprivation. Intracortical disinhibition, but not thalamocortical disinhibition, accompanied this OD plasticity. Both juvenile wild-type mice and adult mice lacking ngr1 in L4 displayed OD plasticity that advanced more rapidly L4 than L2/3 or L5. Interestingly, blocking OD plasticity in L2/3 with the drug AM-251 did not impair OD plasticity in L5. We propose that L4 restricts disinhibition and gates OD plasticity independent of a canonical cortical microcircuit.


Asunto(s)
Plasticidad Neuronal/fisiología , Receptor Nogo 1/genética , Receptor Nogo 1/fisiología , Células Receptoras Sensoriales/fisiología , Corteza Visual/fisiología , Animales , Predominio Ocular , Eliminación de Gen , Ratones , Visión Binocular/fisiología
9.
Biochem Biophys Res Commun ; 378(3): 589-94, 2009 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-19056345

RESUMEN

The effect of the electrical charge or the size of the amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K(+) currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue I313K and I313E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the site was substituted with the smallest neutral amino acid residue: I313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. I313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on the electrical charge or the size of amino acid residue.


Asunto(s)
Sustitución de Aminoácidos , Isoleucina/metabolismo , Canal de Potasio KCNQ1/metabolismo , Sustitución de Aminoácidos/genética , Animales , Células COS , Chlorocebus aethiops , Ácido Glutámico/genética , Ácido Glutámico/metabolismo , Humanos , Isoleucina/genética , Canal de Potasio KCNQ1/agonistas , Canal de Potasio KCNQ1/genética , Lisina/genética , Lisina/metabolismo , Mutación , Porosidad , Electricidad Estática
10.
Cell Rep ; 27(9): 2567-2578.e6, 2019 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-31141683

RESUMEN

Loss-of-function mutations in CNTNAP2 cause a syndromic form of autism spectrum disorder in humans and produce social deficits, repetitive behaviors, and seizures in mice. However, the functional effects of these mutations at cellular and circuit levels remain elusive. Using laser-scanning photostimulation, whole-cell recordings, and electron microscopy, we found a dramatic decrease in excitatory and inhibitory synaptic inputs onto L2/3 pyramidal neurons of the medial prefrontal cortex (mPFC) of Cntnap2 knockout (KO) mice, concurrent with reduced spines and synapses, despite normal dendritic complexity and intrinsic excitability. Moreover, recording of mPFC local field potentials (LFPs) and unit spiking in vivo revealed increased activity in inhibitory neurons, reduced phase-locking to delta and theta oscillations, and delayed phase preference during locomotion. Excitatory neurons showed similar phase modulation changes at delta frequencies. Finally, pairwise correlations increased during immobility in KO mice. Thus, reduced synaptic inputs can yield perturbed temporal coordination of neuronal firing in cortical ensembles.


Asunto(s)
Trastorno Autístico/patología , Dendritas/patología , Proteínas de la Membrana/fisiología , Proteínas del Tejido Nervioso/fisiología , Corteza Prefrontal/patología , Células Piramidales/patología , Sinapsis/patología , Animales , Trastorno Autístico/metabolismo , Dendritas/metabolismo , Modelos Animales de Enfermedad , Potenciales Postsinápticos Excitadores , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Corteza Prefrontal/metabolismo , Células Piramidales/metabolismo , Sinapsis/metabolismo
11.
J Cardiovasc Electrophysiol ; 19(5): 541-9, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18266681

RESUMEN

INTRODUCTION: Slowly activating delayed-rectifier potassium currents in the heart are produced by a complex protein with alpha and beta subunits composed of the potassium voltage-gated channel KQT-like subfamily, member 1 (KCNQ1) and the potassium voltage-gated channel Isk-related family, member 1 (KCNE1), respectively. Mutations in KCNQ1 underlie the most common type of hereditary long QT syndrome (LQTS). Like other potassium channels, KCNQ1 has six transmembrane domains and a highly conserved potassium selectivity filter in the pore helix called "the signature sequence." We aimed to investigate the functional consequences of a newly identified mutation within the signature sequence. METHODS AND RESULTS: Potassium channel genomic DNA from a family with clinical evidence of LQTS was amplified by polymerase chain reaction (PCR), and the resulting products were then sequenced. Three family members had a double-point mutation in KCNQ1 at nucleotides 938 (T-to-A) and 939 (C-to-A), resulting in an isoleucine-to-lysine change at amino acid position 313. These patients displayed prolonged QTc intervals (629, 508, and 500 ms(1/2,) respectively) and repetitive episodes of syncope, but no deafness. Three-dimensional structure modeling of KCNQ1 revealed that this mutation is located at the center of the channel pore. COS-7 cells displayed a lack of current when transfected with a plasmid expressing the mutant. In addition, the mutant displayed a dominant negative effect on current but appeared normal with respect to plasma membrane integration. CONCLUSION: An I313K mutation within the selectivity filter of KCNQ1 results in a dominant-negative loss of channel function, leading to a long QT interval and subsequent syncope.


Asunto(s)
Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Femenino , Predisposición Genética a la Enfermedad/genética , Heterocigoto , Humanos , Persona de Mediana Edad , Mutación/genética , Fenotipo
13.
Nat Neurosci ; 20(3): 389-392, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28114295

RESUMEN

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input.


Asunto(s)
Retroalimentación Fisiológica/fisiología , Lóbulo Frontal/fisiología , Interneuronas/fisiología , Inhibición Neural/fisiología , Péptido Intestinal Vasoactivo/fisiología , Animales , Nivel de Alerta/fisiología , Channelrhodopsins , Femenino , Interneuronas/metabolismo , Locomoción/fisiología , Masculino , Ratones , Ratones Transgénicos , Pupila/fisiología , Células Piramidales/fisiología , Péptido Intestinal Vasoactivo/genética , Péptido Intestinal Vasoactivo/metabolismo
14.
Am J Cardiol ; 98(7): 915-7, 2006 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16996873

RESUMEN

Many clinical studies have evaluated the inflammatory response (mainly interleukin [IL]-6 and C-reactive protein [CRP]) after percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). The aim of this study was to verify the source of possible elevation of IL-6 and CRP after PCI using coronary sinus sampling. We studied 87 subjects who underwent coronary angiography for diagnostic, therapeutic, or follow-up purposes. Blood samples were taken by the PCI team during the catheterization study from the coronary sinus. We measured coronary IL-6 levels by sandwich enzyme-linked immunosorbent assay, and high-sensitivity CRP levels were measured by latex immunonephelometry. The subjects were then classified according to their coronary angiographic findings into non-CAD (no evidence of significant organic CAD), mild CAD (1 vessel narrowed), and severe CAD (>or=2 vessels narrowed) groups. PCI (including stent deployment) was performed in 16 patients with CAD. The mean coronary IL-6 value was higher in the severe than in the mild CAD group (3.67 +/- 2.48 vs 2.3 +/- 1.15 pg/ml, p = 0.027). The mean coronary IL-6 value was higher in the subjects who underwent PCI than in those who did not (2.9 +/- 1.23 vs 1.87 +/- 0.9 pg/ml, p = 0.037), and the same was found regarding CRP (1.244 +/- 0.72 vs 0.498 +/- 0.51 mg/L, p = 0.032). The coronary IL-6 values correlated positively with the coronary CRP values (r = 0.374, p = 0.017). In conclusion, the increase in coronary IL-6 and CRP levels after PCI in patients with CAD might be attributed to their release from the coronary atheroma secondary to the direct mechanical effect applied on the atheroma itself by balloon inflation and stent deployment.


Asunto(s)
Angioplastia Coronaria con Balón , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/terapia , Interleucina-6/sangre , Anciano , Circulación Coronaria , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad
15.
Nat Commun ; 7: 12829, 2016 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-27611660

RESUMEN

Perisomatic inhibition of pyramidal neurons is established by fast-spiking, parvalbumin-expressing interneurons (PV cells). Failure to assemble adequate perisomatic inhibition is thought to underlie the aetiology of neurological dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we show that in mouse visual cortex, strong perisomatic inhibition does not develop if PV cells lack a single copy of Pten. PTEN signalling appears to drive the assembly of perisomatic inhibition in an experience-dependent manner by suppressing the expression of EphB4; PV cells hemizygous for Pten show an ∼2-fold increase in expression of EphB4, and over-expression of EphB4 in adult PV cells causes a dismantling of perisomatic inhibition. These findings implicate a molecular disinhibitory mechanism driving the establishment of perisomatic inhibition whereby visual experience enhances Pten signalling, resulting in the suppression of EphB4 expression; this relieves a native synaptic repulsion between PV cells and pyramidal neurons, thereby promoting the assembly of perisomatic inhibition.


Asunto(s)
Neuronas/fisiología , Fosfohidrolasa PTEN/metabolismo , Receptor EphB4/metabolismo , Corteza Visual/fisiología , Animales , Embrión de Mamíferos , Eliminación de Gen , Regulación de la Expresión Génica/fisiología , Luz , Ratones , Mutación , Fosfohidrolasa PTEN/genética , Parvalbúminas/metabolismo , Células Piramidales , Receptor EphB4/genética , Transducción de Señal
16.
Neuron ; 92(1): 160-173, 2016 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-27641496

RESUMEN

Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity.


Asunto(s)
Predominio Ocular/fisiología , Neurregulina-1/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Receptor ErbB-4/fisiología , Corteza Visual/fisiología , Animales , Período Crítico Psicológico , Regulación hacia Abajo/fisiología , Femenino , Masculino , Ratones , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Neurregulina-1/farmacología , Plasticidad Neuronal/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Parvalbúminas/metabolismo , Privación Sensorial/fisiología , Corteza Visual/crecimiento & desarrollo
17.
J Comp Neurol ; 522(9): 2191-208, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24357090

RESUMEN

Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus.


Asunto(s)
Hipocampo/crecimiento & desarrollo , Hipocampo/fisiología , Animales , Hipocampo/citología , Hipocampo/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones Endogámicos C57BL , Microelectrodos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Estimulación Luminosa , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Células Piramidales/crecimiento & desarrollo , Células Piramidales/fisiología , Receptores de GABA-B/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/efectos de los fármacos , Sinapsis/fisiología , Técnicas de Cultivo de Tejidos , Imagen de Colorante Sensible al Voltaje
18.
J Comp Neurol ; 522(6): 1333-54, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24166578

RESUMEN

The hippocampal CA2 subfield was initially identified by Lorente de Nó as an anatomically distinct region based on its cytoarchitectural features. Although there is an enormous body of literature on other hippocampal subfields (CA1 and CA3), relatively little is known about the physiological and developmental properties of CA2. Here we report identification of the CA2 region in the mouse by immunostaining with a Purkinje cell protein 4 (PCP4) antibody, which effectively delineates CA3/CA2 and CA2/CA1 borders and agrees well with previous cytoarchitectural definitions of CA2. The PCP4 immunostaining-delineated CA2 neurons have distinguishable differences in cell morphology, physiology, and synaptic circuit connections compared with distal CA3 and proximal CA1 regions. The average somatic sizes of excitatory cells differ across CA1-3, with the smallest to largest somatic size being CA1

Asunto(s)
Región CA2 Hipocampal/crecimiento & desarrollo , Región CA2 Hipocampal/metabolismo , Regulación de la Expresión Génica/genética , Proteínas del Tejido Nervioso/metabolismo , Análisis de Varianza , Animales , Animales Recién Nacidos , Región CA2 Hipocampal/citología , Calbindina 2/genética , Proteínas de Unión al Calcio/metabolismo , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Técnicas In Vitro , Proteínas Luminiscentes/genética , Potenciales de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuronas/metabolismo , Neuronas/fisiología
19.
Lab Chip ; 13(4): 536-41, 2013 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-23044655

RESUMEN

Microfluidic technology is emerging as a useful tool for the study of brain slices, offering precise delivery of chemical factors along with robust oxygen and nutrient transport. However, continued reliance upon electrode-based physiological recording poses inherent limitations in terms of physical access, as well as the number of sites that can be sampled simultaneously. In the present study, we combine a microfluidic laminar flow chamber with fast voltage-sensitive dye imaging and laser photostimulation via caged glutamate to map neural network activity across large cortical regions in living brain slices. We find that the closed microfluidic chamber results in greatly improved signal-to-noise performance for optical measurements of neural signaling. These optical tools are also leveraged to characterize laminar flow interfaces within the device, demonstrating a functional boundary width of less than 100 µm. Finally, we utilize this integrated platform to investigate the mechanism of signal propagation for spontaneous neural activity in the developing mouse hippocampus. Through the use of localized Ca(2+) depletion, we provide evidence for Ca(2+)-dependent synaptic transmission.


Asunto(s)
Corteza Cerebral/fisiología , Hipocampo/fisiología , Técnicas Analíticas Microfluídicas , Óptica y Fotónica , Animales , Corteza Cerebral/citología , Hipocampo/citología , Ratones , Técnicas Analíticas Microfluídicas/instrumentación
20.
Front Neural Circuits ; 7: 204, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24421758

RESUMEN

Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG) such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL) is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD) imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern separation.


Asunto(s)
Giro Dentado/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Giro Dentado/citología , Potenciales Postsinápticos Inhibidores/fisiología , Ratones , Potenciales Postsinápticos Miniatura/fisiología , Inhibición Neural/fisiología , Plasticidad Neuronal/fisiología , Neuronas/citología , Sinapsis/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA