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1.
Clin Oral Implants Res ; 34(7): 684-697, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37139538

RESUMEN

OBJECTIVES: To study clinical and radiographic outcomes after non-surgical treatment of peri-implantitis using either an oscillating chitosan brush (OCB) or titanium curette (TC) and to observe changes in clinical signs of inflammation after repeated treatment. METHODS: Thirty-nine patients with dental implants (n = 39) presented with radiographic bone level (RBL) of 2-4 mm, bleeding index (BI) ≥ 2, and probing pocket depth (PPD) ≥ 4 mm were randomly assigned to mechanical debridement with OCB (test) or TC (control). Treatment was performed at baseline and repeated at 3, 6, and 9 months in cases with > 1 implant site with BI ≥ 1 and PPD≥4 mm. Blinded examiners recorded PPD, BI, pus, and plaque. The radiographic bone level change between baseline and 12 months was calculated. A multistate model was used to calculate transitions of BI. RESULTS: Thirty-one patients completed the study. Both groups exhibited a significant reduction in PPD, BI, and pus at 12 months compared to baseline. Radiographic analysis showed stable mean RBL in both groups at 12 months. There was no statistically significant difference in any of the parameters between the groups. CONCLUSIONS: Within the limitations of this 12-month multicenter randomized clinical trial, non-surgical treatment of peri-implantitis with OCB or TC showed no statistically significant differences between the groups. Clinical improvements and, in some cases, disease resolution, was observed in both groups. However, persistent inflammation was a common finding which further puts emphasis on the need for further treatment.


Asunto(s)
Quitosano , Implantes Dentales , Periimplantitis , Humanos , Periimplantitis/diagnóstico por imagen , Periimplantitis/terapia , Quitosano/uso terapéutico , Titanio/uso terapéutico , Estudios de Seguimiento , Resultado del Tratamiento , Inflamación , Supuración/inducido químicamente , Implantes Dentales/efectos adversos
2.
Clin Oral Implants Res ; 33(12): 1254-1264, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36207993

RESUMEN

OBJECTIVES: This prospective, parallel-group, examiner-blinded, multicentre, randomized, controlled clinical trial aimed to assess the efficacy of an oscillating chitosan brush (OCB) versus titanium curettes (TC) on clinical parameters in the non-surgical treatment of peri-implantitis. MATERIAL AND METHODS: In five dental specialist clinics, 39 patients with one implant with mild to moderate peri-implantitis, defined as 2-4 mm radiographic reduced bone level, bleeding index (BI) ≥ 2, and probing pocket depth (PPD) ≥ 4 mm were randomly allocated to test and control groups, receiving OCB or TC debridement, respectively. Treatment was performed at baseline and three months. PPD, BI, and Plaque index (PI) were measured at six sites per implant and recorded by five blinded examiners at baseline, one, three, and six month(s). Pus was recorded as present/not present. Changes in PPD and BI were compared between groups and analysed using multilevel partial ordinal and linear regression. RESULTS: Thirty-eight patients completed the study. Both groups showed significant reductions in PPD and BI at six months compared with baseline (p < .05). There was no statistically significant difference in PPD and BI changes between the groups. Eradication of peri-implant disease as defined was observed in 9.5% of cases in the OCB group and 5.9% in the TC group. CONCLUSIONS: Within the limitations of this six-month multicentre clinical trial, non-surgical treatment of peri-implantitis with OCB and TC showed no difference between the interventions. Eradication of disease was not predictable for any of the groups.


Asunto(s)
Quitosano , Periimplantitis , Humanos , Quitosano/uso terapéutico , Periimplantitis/diagnóstico por imagen , Periimplantitis/terapia , Estudios Prospectivos , Titanio
3.
Eur J Neurosci ; 51(11): 2236-2249, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31872480

RESUMEN

Change in linguistic prosody generates a mismatch negativity response (MMN), indicating neural representation of linguistic prosody, while change in affective prosody generates a positive response (P3a), reflecting its motivational salience. However, the neural response to concurrent affective and linguistic prosody is unknown. The present paper investigates the integration of these two prosodic features in the brain by examining the neural response to separate and concurrent processing by electroencephalography (EEG). A spoken pair of Swedish words-['fɑ́ːsɛn] phase and ['fɑ̀ːsɛn] damn-that differed in emotional semantics due to linguistic prosody was presented to 16 subjects in an angry and neutral affective prosody using a passive auditory oddball paradigm. Acoustically matched pseudowords-['vɑ́ːsɛm] and ['vɑ̀ːsɛm]-were used as controls. Following the constructionist concept of emotions, accentuating the conceptualization of emotions based on language, it was hypothesized that concurrent affective and linguistic prosody with the same valence-angry ['fɑ̀ːsɛn] damn-would elicit a unique late EEG signature, reflecting the temporal integration of affective voice with emotional semantics of prosodic origin. In accordance, linguistic prosody elicited an MMN at 300-350 ms, and affective prosody evoked a P3a at 350-400 ms, irrespective of semantics. Beyond these responses, concurrent affective and linguistic prosody evoked a late positive component (LPC) at 820-870 ms in frontal areas, indicating the conceptualization of affective prosody based on linguistic prosody. This study provides evidence that the brain does not only distinguish between these two functions of prosody but also integrates them based on language and experience.


Asunto(s)
Emociones , Percepción del Habla , Mapeo Encefálico , Electroencefalografía , Humanos , Lingüística , Semántica
4.
Curr Biol ; 29(15): 2477-2487.e6, 2019 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-31353184

RESUMEN

The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here, we show that cochlear rhythms are system driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Because the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level, suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses.


Asunto(s)
Relojes Circadianos/fisiología , Cóclea/fisiología , Dexametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Ruido , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Animales , Dexametasona/metabolismo , Glucocorticoides/metabolismo , Masculino , Ratones , Núcleo Supraquiasmático/fisiología , Núcleo Supraquiasmático/cirugía
5.
J Anim Sci ; 97(5): 2188-2201, 2019 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-30796804

RESUMEN

Effects of whole-crop barley and grass silages harvested at different maturity stages, with or without protein supplementation, on intake, in vivo digestibility, feces characteristics, and protein utilization in wethers were evaluated. Whole-crop barley silage harvested at heading stage (BH) and at medium milk stage (BM), grass silage (GE) taken at the flag leaf-early heading stage, and grass silage (GL) taken at medium-late heading stage were fed to eight wethers in two 4 × 4 Latin squares. Wethers in one square were fed supplementary rapeseed meal. Experimental periods lasted for 4 wk and wethers were fed ad libitum during the first 3 wk, with intake recorded during the third week. During the fourth week, wethers were fed 80% of ad libitum, and feces and urine were collected during the last 4 d. The GE and BH diets had greater (P < 0.05) in vivo apparent digestibility of DM and its nutrients, lower proportion of fecal particle DM (PDM) with a greater proportion of small particles compared with GL and BM diets, respectively. The GE diet had greater (P < 0.001) in vitro OM digestibility and in vivo digestibility of OM and fibre, resulting in a smaller (P < 0.001) proportion of PDM with a greater (P < 0.001) proportion of small particles compared with the other diets. In vivo NDF digestibility was negatively related to fecal PDM across forage types (R2 = 0.91, RMSE = 2.55). The GE silage had greater CP concentration, and animals fed the GE diet had greater intake of CP (P < 0.001) and sum of the degradable CP fractions A, B1, and B2 (P < 0.01), resulting in greater (P < 0.05) urinary nitrogen (N) excretion than when fed any of the other diets and a lower (P < 0.05) N retention compared with BH and BM diets. Microbial N supply tended to increase when animals were fed the BH diet (P = 0.10) and when rapeseed meal was added to the forages (P = 0.08). Increased N intake (P = 0.008) by rapeseed meal supplementation increased urinary N excretion in gram per day (P = 0.05). The strong relationship between in vivo NDF digestibility and fecal PDM indicates potentials for using PDM as a cheap method to predict NDF digestibility. Early harvest of the forages improved in vivo digestibility of nutrients, resulting in less fecal PDM with a greater proportion of small particles compared with late harvest within forage type. However, wethers fed the GE diet had greater urinary N losses compared with wethers fed the GL diet but this effect of maturity was absent when fed whole-crop barley silage.


Asunto(s)
Fibras de la Dieta/metabolismo , Hordeum , Poaceae , Ovinos/fisiología , Ensilaje/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos , Digestión , Ingestión de Alimentos , Heces/química , Masculino
6.
Eur J Neurosci ; 48(4): 2030-2049, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30019495

RESUMEN

Communication sounds across all mammals consist of multiple frequencies repeated in sequence. The onset and offset of vocalizations are potentially important cues for recognizing distinct units, such as phonemes and syllables, which are needed to perceive meaningful communication. The superior paraolivary nucleus (SPON) in the auditory brainstem has been implicated in the processing of rhythmic sounds. Here, we compared how best frequency tones (BFTs), broadband noise (BBN), and natural mouse calls elicit onset and offset spiking in the mouse SPON. The results demonstrate that onset spiking typically occurs in response to BBN, but not BFT stimulation, while spiking at the sound offset occurs for both stimulus types. This effect of stimulus bandwidth on spiking is consistent with two of the established inputs to the SPON from the octopus cells (onset spiking) and medial nucleus of the trapezoid body (offset spiking). Natural mouse calls elicit two main spiking peaks. The first spiking peak, which is weak or absent with BFT stimulation, occurs most consistently during the call envelope, while the second spiking peak occurs at the call offset. This suggests that the combined spiking activity in the SPON elicited by vocalizations reflects the entire envelope, that is, the coarse amplitude waveform. Since the output from the SPON is purely inhibitory, it is speculated that, at the level of the inferior colliculus, the broadly tuned first peak may improve the signal-to-noise ratio of the subsequent, more call frequency-specific peak. Thus, the SPON may provide a dual inhibition mechanism for tracking phonetic boundaries in social-vocal communication.


Asunto(s)
Percepción Auditiva/fisiología , Complejo Olivar Superior/fisiología , Vocalización Animal , Acústica , Potenciales de Acción/fisiología , Animales , Electrocorticografía , Femenino , Masculino , Ratones , Ratones Endogámicos CBA , Neuronas/fisiología , Factores de Tiempo
7.
Front Neural Circuits ; 11: 37, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28620283

RESUMEN

Auditory streaming enables perception and interpretation of complex acoustic environments that contain competing sound sources. At early stages of central processing, sounds are segregated into separate streams representing attributes that later merge into acoustic objects. Streaming of temporal cues is critical for perceiving vocal communication, such as human speech, but our understanding of circuits that underlie this process is lacking, particularly at subcortical levels. The superior paraolivary nucleus (SPON), a prominent group of inhibitory neurons in the mammalian brainstem, has been implicated in processing temporal information needed for the segmentation of ongoing complex sounds into discrete events. The SPON requires temporally precise and robust excitatory input(s) to convey information about the steep rise in sound amplitude that marks the onset of voiced sound elements. Unfortunately, the sources of excitation to the SPON and the impact of these inputs on the behavior of SPON neurons have yet to be resolved. Using anatomical tract tracing and immunohistochemistry, we identified octopus cells in the contralateral cochlear nucleus (CN) as the primary source of excitatory input to the SPON. Cluster analysis of miniature excitatory events also indicated that the majority of SPON neurons receive one type of excitatory input. Precise octopus cell-driven onset spiking coupled with transient offset spiking make SPON responses well-suited to signal transitions in sound energy contained in vocalizations. Targets of octopus cell projections, including the SPON, are strongly implicated in the processing of temporal sound features, which suggests a common pathway that conveys information critical for perception of complex natural sounds.


Asunto(s)
Núcleo Coclear/citología , Neuronas/fisiología , Complejo Olivar Superior/citología , Complejo Olivar Superior/fisiología , Anestesia General , Animales , Estado de Conciencia/efectos de los fármacos , Estado de Conciencia/fisiología , Neuronas/efectos de los fármacos
8.
Neuroscience ; 337: 315-330, 2016 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-27651152

RESUMEN

The leading treatments for severe hearing disabilities work on the principle of conveying electrical pulses to the auditory brainstem that enable perception of speech. It is currently not known how well the brainstem neurons specialized for decoding such coarse sound information develop when deprived of auditory input activity. Here, we used congenitally deaf α1D-/- mice, lacking activity in the auditory nerve, to investigate the superior paraolivary nucleus (SPON) - a prominent mammalian brainstem structure that responds selectively to sound pulses by rebound spiking. Whole-cell patch-clamp recordings from SPON neurons in the α1D-/- and control mice were obtained at equivalent pre- and post-hearing onset ages. The results show that SPON neurons in the α1D-/- display less precise, plateau-like rebound spiking compared to control neurons. However, the rebound spiking mechanism undergoes strong compensation with age in the α1D-/-. Voltage-activated Ca2+-currents lower the spike threshold, rescuing the capacity for spike initiation at pre-hearing onset ages. Gradual up-regulation of the inwardly rectifying h-current contributes to depolarize the membrane potential. Reduction of the membrane time constant and less recruitment of Ca2+-currents thereby normalize precise rebound spiking at post-hearing onset ages. We found the soluble form of the neurotrophic factor neuritin to be up-regulated in SPON of deaf mice, which may have promoted neuronal survival and prolonged plasticity of the SPON circuitry. A stereotyped timeline of compensation of rebound spiking in deaf SPON neurons indicates robust intrinsic regulation of the brainstem circuitry encoding sound rhythms. This may be a prerequisite for successful cochlear implants.


Asunto(s)
Potenciales de Acción/fisiología , Vías Auditivas/fisiología , Audición/fisiología , Neuronas/fisiología , Núcleo Olivar/fisiología , Estimulación Acústica/métodos , Animales , Vías Auditivas/crecimiento & desarrollo , Percepción Auditiva/fisiología , Ratones , Plasticidad Neuronal , Núcleo Olivar/crecimiento & desarrollo , Tiempo de Reacción/fisiología
9.
Neuroscience ; 334: 1-12, 2016 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-27476438

RESUMEN

The superior paraolivary nucleus (SPON) is a prominent structure in the mammalian auditory brainstem with a proposed role in encoding transient broadband sounds such as vocalized utterances. Currently, the source of excitatory pathways that project to the SPON and how these inputs contribute to SPON function are poorly understood. To shed light on the nature of these inputs, we measured evoked excitatory postsynaptic currents (EPSCs) in the SPON originating from the intermediate acoustic stria and compared them with the properties of EPSCs in the lateral superior olive (LSO) originating from the ventral acoustic stria during auditory development from postnatal day 5 to 22 in mice. Before hearing onset, EPSCs in the SPON and LSO are very similar in size and kinetics. After the onset of hearing, SPON excitation is refined to extremely few (2:1) fibers, with each strengthened by an increase in release probability, yielding fast and strong EPSCs. LSO excitation is recruited from more fibers (5:1), resulting in strong EPSCs with a comparatively broader stimulus-response range after hearing onset. Evoked SPON excitation is comparatively weaker than evoked LSO excitation, likely due to a larger fraction of postsynaptic GluR2-containing Ca2+-impermeable AMPA receptors after hearing onset. Taken together, SPON excitation develops synaptic properties that are suited for transmitting single events with high temporal reliability and the strong, dynamic LSO excitation is compatible with high rate-level sensitivity. Thus, the excitatory input pathways to the SPON and LSO mature to support different decoding strategies of respective coarse temporal and sound intensity information at the brainstem level.


Asunto(s)
Percepción Auditiva/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Núcleo Olivar/crecimiento & desarrollo , Núcleo Olivar/fisiología , Complejo Olivar Superior/crecimiento & desarrollo , Complejo Olivar Superior/fisiología , Animales , Animales Recién Nacidos , Vías Auditivas/efectos de los fármacos , Vías Auditivas/crecimiento & desarrollo , Vías Auditivas/fisiología , Percepción Auditiva/efectos de los fármacos , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Ratones Endogámicos CBA , Neurotransmisores/farmacología , Núcleo Olivar/efectos de los fármacos , Técnicas de Placa-Clamp , Receptores AMPA/metabolismo , Complejo Olivar Superior/efectos de los fármacos , Técnicas de Cultivo de Tejidos
10.
Brain Struct Funct ; 220(5): 2639-52, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24973970

RESUMEN

The mammalian superior paraolivary nucleus (SPON) is a major source of GABAergic inhibition to neurons in the inferior colliculus (IC), a well-studied midbrain nucleus that is the site of convergence and integration for the majority ascending auditory pathways en route to the cortex. Neurons in the SPON and IC exhibit highly precise responses to temporal sound features, which are important perceptual cues for naturally occurring sounds. To determine how inhibitory input from the SPON contributes to the encoding of temporal information in the IC, a reversible inactivation procedure was conducted to silence SPON neurons, while recording responses to amplitude-modulated tones and silent gaps between tones in the IC. The results show that SPON-derived inhibition shapes responses of onset and sustained units in the IC via different mechanisms. Onset neurons appear to be driven primarily by excitatory inputs and their responses are shaped indirectly by SPON-derived inhibition, whereas sustained neurons are heavily influenced directly by transient offset inhibition from the SPON. The findings also demonstrate that a more complete dissection of temporal processing pathways is critical for understanding how biologically important sounds are encoded by the brain.


Asunto(s)
Vías Auditivas/fisiología , Colículos Inferiores/fisiología , Neuronas/fisiología , Núcleo Olivar/fisiología , Complejo Olivar Superior/fisiología , Estimulación Acústica/métodos , Potenciales de Acción/fisiología , Animales , Mapeo Encefálico , Ratas Sprague-Dawley
11.
PLoS One ; 9(5): e98277, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24867596

RESUMEN

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <-75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs.


Asunto(s)
Tronco Encefálico/metabolismo , Colina O-Acetiltransferasa/genética , Neuronas Eferentes/fisiología , Potenciales de Acción , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Técnicas de Placa-Clamp , Vestíbulo del Laberinto/fisiología
12.
J Neurophysiol ; 109(11): 2691-704, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23515791

RESUMEN

The superior paraolivary nucleus (SPON) is a prominent cell group in the auditory brain stem that has been increasingly implicated in representing temporal sound structure. Although SPON neurons selectively respond to acoustic signals important for sound periodicity, the underlying physiological specializations enabling these responses are poorly understood. We used in vitro and in vivo recordings to investigate how SPON neurons develop intrinsic cellular properties that make them well suited for encoding temporal sound features. In addition to their hallmark rebound spiking at the stimulus offset, SPON neurons were characterized by spiking patterns termed onset, adapting, and burst in response to depolarizing stimuli in vitro. Cells with burst spiking had some morphological differences compared with other SPON neurons and were localized to the dorsolateral region of the nucleus. Both membrane and spiking properties underwent strong developmental regulation, becoming more temporally precise with age for both onset and offset spiking. Single-unit recordings obtained in young mice demonstrated that SPON neurons respond with temporally precise onset spiking upon tone stimulation in vivo, in addition to the typical offset spiking. Taken together, the results of the present study demonstrate that SPON neurons develop sharp on-off spiking, which may confer sensitivity to sound amplitude modulations or abrupt sound transients. These findings are consistent with the proposed involvement of the SPON in the processing of temporal sound structure, relevant for encoding communication cues.


Asunto(s)
Potenciales Evocados Auditivos , Neuronas/fisiología , Núcleo Olivar/fisiología , Factores de Edad , Animales , Potenciales de la Membrana , Ratones , Ratones Endogámicos C57BL , Neuronas/clasificación , Núcleo Olivar/citología , Núcleo Olivar/crecimiento & desarrollo
13.
PLoS Curr ; 52013 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-24459609

RESUMEN

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral innate immune activation have been described as features of the disease. Isolated human HD monocytes have been shown to produce more cytokines upon LPS stimulation compared to control monocytes. Understanding alterations in the signalling cascades responsible and activated by this increase in pro-inflammatory cytokine production is crucial in understanding the molecular basis of this phenomenon. Here we investigated the signalling cascade most commonly activated by pro-inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow cytometry, we show that one out of three key transcription factors activated by JAK/STAT signalling is altered in primary human HD innate immune cells, suggesting that this pathway may only play a minor, additive role in the immune cell dysfunction in HD.

14.
J Neurophysiol ; 108(9): 2629-39, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22896724

RESUMEN

In a single-electrode current-clamp recording, the measured potential includes both the response of the membrane and that of the measuring electrode. The electrode response is traditionally removed using bridge balance, where the response of an ideal resistor representing the electrode is subtracted from the measurement. Because the electrode is not an ideal resistor, this procedure produces capacitive transients in response to fast or discontinuous currents. More sophisticated methods exist, but they all require a preliminary calibration phase, to estimate the properties of the electrode. If these properties change after calibration, the measurements are corrupted. We propose a compensation method that does not require preliminary calibration. Measurements are compensated offline by fitting a model of the neuron and electrode to the trace and subtracting the predicted electrode response. The error criterion is designed to avoid the distortion of compensated traces by spikes. The technique allows electrode properties to be tracked over time and can be extended to arbitrary models of electrode and neuron. We demonstrate the method using biophysical models and whole cell recordings in cortical and brain-stem neurons.


Asunto(s)
Técnicas de Placa-Clamp/métodos , Animales , Calibración , Potenciales de la Membrana , Ratones , Microelectrodos , Células Piramidales/fisiología
15.
J Neurosci ; 32(1): 133-42, 2012 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-22219276

RESUMEN

Huntington's disease (HD) is caused by an expanded polyglutamine tract in the protein huntingtin (htt). Although HD has historically been viewed as a brain-specific disease, htt is expressed ubiquitously, and recent studies indicate that mutant htt might cause changes to the immune system that could contribute to pathogenesis. Monocytes from HD patients and mouse models are hyperactive in response to stimulation, and increased levels of inflammatory cytokines and chemokines are found in pre-manifest patients that correlate with pathogenesis. In this study, wild-type (WT) bone marrow cells were transplanted into two lethally irradiated transgenic mouse models of HD that ubiquitously express full-length htt (YAC128 and BACHD mice). Bone marrow transplantation partially attenuated hypokinetic and motor deficits in HD mice. Increased levels of synapses in the cortex were found in HD mice that received bone marrow transplants. Importantly, serum levels of interleukin-6, interleukin-10, CXC chemokine ligand 1, and interferon-γ were significantly higher in HD than WT mice but were normalized in mice that received a bone marrow transplant. These results suggest that immune cell dysfunction might be an important modifier of pathogenesis in HD.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/terapia , Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea/métodos , Enfermedad de Huntington/inmunología , Enfermedad de Huntington/terapia , Terapia de Inmunosupresión/métodos , Animales , Enfermedades Autoinmunes del Sistema Nervioso/fisiopatología , Modelos Animales de Enfermedad , Femenino , Humanos , Enfermedad de Huntington/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
16.
J Neurosci ; 31(47): 17193-206, 2011 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-22114286

RESUMEN

How do neurons compute? Two main theories compete: neurons could temporally integrate noisy inputs (rate-based theories) or they could detect coincident input spikes (spike timing-based theories). Correlations at fine timescales have been observed in many areas of the nervous system, but they might have a minor impact. To address this issue, we used a probabilistic approach to quantify the impact of coincidences on neuronal response in the presence of fluctuating synaptic activity. We found that when excitation and inhibition are balanced, as in the sensory cortex in vivo, synchrony in a very small proportion of inputs results in dramatic increases in output firing rate. Our theory was experimentally validated with in vitro recordings of cortical neurons of mice. We conclude that not only are noisy neurons well equipped to detect coincidences, but they are so sensitive to fine correlations that a rate-based description of neural computation is unlikely to be accurate in general.


Asunto(s)
Potenciales de Acción/fisiología , Neuronas/fisiología , Animales , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Técnicas de Cultivo de Órganos , Células Piramidales/fisiología
17.
J Neurosci ; 31(35): 12566-78, 2011 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-21880918

RESUMEN

The superior paraolivary nucleus (SPON) is a prominent structure in the auditory brainstem. In contrast to the principal superior olivary nuclei with identified roles in processing binaural sound localization cues, the role of the SPON in hearing is not well understood. A combined in vitro and in vivo approach was used to investigate the cellular properties of SPON neurons in the mouse. Patch-clamp recordings in brain slices revealed that brief and well timed postinhibitory rebound spiking, generated by the interaction of two subthreshold-activated ion currents, is a hallmark of SPON neurons. The I(h) current determines the timing of the rebound, whereas the T-type Ca(2+) current boosts the rebound to spike threshold. This precisely timed rebound spiking provides a physiological explanation for the sensitivity of SPON neurons to sinusoidally amplitude-modulated (SAM) tones in vivo, where peaks in the sound envelope drive inhibitory inputs and SPON neurons fire action potentials during the waveform troughs. Consistent with this notion, SPON neurons display intrinsic tuning to frequency-modulated sinusoidal currents (1-15Hz) in vitro and discharge with strong synchrony to SAMs with modulation frequencies between 1 and 20 Hz in vivo. The results of this study suggest that the SPON is particularly well suited to encode rhythmic sound patterns. Such temporal periodicity information is likely important for detection of communication cues, such as the acoustic envelopes of animal vocalizations and speech signals.


Asunto(s)
Potenciales de Acción/fisiología , Inhibición Neural/fisiología , Neuronas/fisiología , Núcleo Olivar/citología , Sonido , Estimulación Acústica/métodos , Anestésicos Locales/farmacología , Animales , Animales Recién Nacidos , Vías Auditivas/fisiología , Biofisica , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Estimulación Eléctrica , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Técnicas In Vitro , Canales Iónicos/metabolismo , Lidocaína/análogos & derivados , Lidocaína/farmacología , Mibefradil/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Periodicidad , Canales de Potasio/metabolismo , Psicoacústica , Pirimidinas/farmacología , Tiempo de Reacción/fisiología , Tetrodotoxina/farmacología
18.
PLoS Curr ; 3: RRN1231, 2011 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-21826115

RESUMEN

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. Immune activation is a well-established feature of the HD brain and we have previously demonstrated a widespread, progressive innate immune response detectable in plasma throughout the course of HD. In the present work we used multiplex ELISA to quantify levels of chemokines in plasma from controls and subjects at different stages of HD. We found an altered chemokine profile tracking with disease progression, with significant elevations of five chemokines (eotaxin-3, MIP-1ß, eotaxin, MCP-1 and MCP-4) while three (eotaxin-3, MIP-1ß and eotaxin) showed significant linear increases across advancing disease stages. We validated our results in a separate sample cohort including subjects at different stages of HD. Here we saw that chemokine levels (MCP-1 and eotaxin) correlated with clinical scores. We conclude that, like cytokines, chemokines may be linked to the pathogenesis of HD, and that immune molecules may be valuable in tracking and exploring the pathogenesis of HD.

19.
Biophys J ; 100(7): 1627-34, 2011 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-21463575

RESUMEN

Tones cause vibrations within the hearing organ. Conventionally, these vibrations are thought to reflect the input and therefore end with the stimulus. However, previous recordings of otoacoustic emissions and cochlear microphonic potentials suggest that the organ of Corti does continue to move after the end of a tone. These after-vibrations are characterized here through recordings of basilar membrane motion and hair cell extracellular receptor potentials in living anesthetized guinea pigs. We show that after-vibrations depend on the level and frequency of the stimulus, as well as on the sensitivity of the ear. Even a minor loss of hearing sensitivity caused a sharp reduction in after-vibration amplitude and duration. Mathematical models suggest that after-vibrations are driven by energy added into organ of Corti motion after the end of an acoustic stimulus. The possible importance of after-vibrations for psychophysical phenomena such as forward masking and gap detection are discussed.


Asunto(s)
Estimulación Acústica , Oído Interno/fisiología , Sonido , Potenciales de Acción/fisiología , Animales , Membrana Basilar/fisiología , Cobayas , Movimiento (Física) , Órgano Espiral/fisiología , Factores de Tiempo , Vibración
20.
Front Neurosci ; 5: 9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21415925

RESUMEN

Computational modeling is increasingly used to understand the function of neural circuits in systems neuroscience. These studies require models of individual neurons with realistic input-output properties. Recently, it was found that spiking models can accurately predict the precisely timed spike trains produced by cortical neurons in response to somatically injected currents, if properly fitted. This requires fitting techniques that are efficient and flexible enough to easily test different candidate models. We present a generic solution, based on the Brian simulator (a neural network simulator in Python), which allows the user to define and fit arbitrary neuron models to electrophysiological recordings. It relies on vectorization and parallel computing techniques to achieve efficiency. We demonstrate its use on neural recordings in the barrel cortex and in the auditory brainstem, and confirm that simple adaptive spiking models can accurately predict the response of cortical neurons. Finally, we show how a complex multicompartmental model can be reduced to a simple effective spiking model.

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