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BACKGROUND: Touch is a crucial sense for perceiving the spatial characteristics of objects. The JVP dome was developed to evaluate tactile spatial acuity using a grating orientation task. There were few studies depicting sequences and details for the entire task, including practice, training, and testing sessions. Therefore, we proposed and elaborated a protocol for the grating orientation task using the staircase method, which required fewer testing trials compared with the method of constant stimuli. METHODS: Twenty-three healthy participants were enrolled in this experiment. The JVP domes with 11 different groove widths were used. Tactile discrimination thresholds were estimated using a two-down-one-up staircase method. The experiment comprised practice, training, and testing sessions, conducted by trained examiners who performed grating stimulation on participants' index fingerpads. RESULTS: All participants passed the required accuracy in the practice and training sessions. Eight transition points were obtained in the testing session for each participant. The tactile discrimination thresholds were determined from the last six transition points. We obtained the mean tactile discrimination threshold as 1.8 ± 0.75 mm (n = 23). The results demonstrated that the proposed protocol was successfully applied to assess tactile discrimination thresholds. CONCLUSIONS: The present study investigated the protocol of grating orientation tasks requiring a small number of testing trials with the assurance of the task quality. The feasibility study and preliminary results indicated the potentiality of this protocol for future clinical application.
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Percepción del Tacto , Tacto , Humanos , Tacto/fisiología , Estudios de Factibilidad , Percepción del Tacto/fisiologíaRESUMEN
BACKGROUND: Stroke and spinal cord injury are neurological disorders that cause disability and exert tremendous social and economic effects. Robot-assisted training (RAT), which may reduce spasticity, is widely applied in neurorehabilitation. The combined effects of RAT and antispasticity therapies, such as botulinum toxin A injection therapy, on functional recovery remain unclear. This review evaluated the effects of combined therapy on functional recovery and spasticity reduction. MATERIALS AND METHODS: Studies evaluating the efficacy of RAT and antispasticity therapy in promoting functional recovery and reducing spasticity were systemically reviewed. Five randomized controlled trials (RCTs) were included. The modified Jadad scale was applied for quality assessment. Functional assessments, such as the Berg Balance Scale, were used to measure the primary outcome. Spasticity assessments, such as the modified Ashworth Scale, were used to measure the secondary outcome. RESULTS: Combined therapy improves functional recovery in the lower limbs but does not reduce spasticity in the upper or lower limbs. CONCLUSIONS: The evidence supports that combined therapy improves lower limb function but does not reduce spasticity. The considerable risk of bias among the included studies and the enrolled patients who did not receive interventions within the golden period of intervention are two major factors that should be considered when interpreting these results. Additional high-quality RCTs are required.
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Several methods for the measurement of tactile acuity have been devised previously, but unexpected nonspatial cues and intensive manual skill requirements compromise measurement accuracy. Therefore, we must urgently develop an automated, accurate, and noninvasive method for assessing tactile acuity. The present study develops a novel method applying a robotic tactile stimulator to automatically measure tactile acuity that comprises eye-opened, eye-closed training, and testing sessions. Healthy participants judge the orientation of a rotating grating ball presented on their index fingerpads in a two-alternative forced-choice task. A variable rotation speed of 5, 10, 40, or 160 mm/s was used for the tactile measurement at a variety of difficulties. All participants met the passing criteria for the training experiment. Performance in orientation identification, quantified by the proportion of trials with correct answers, differed across scanning directions, with the highest rotation speed (160 mm/s) having the worst performance. Accuracy did not differ between vertical and horizontal orientations. Our results demonstrated the utility of the pre-test training protocol and the functionality of the developed procedure for tactile acuity assessment. The novel protocol performed well when applied to the participants. Future studies will be conducted to apply this method to patients with impairment of light touch.
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Señales (Psicología) , Robótica , Humanos , Voluntarios Sanos , RotaciónRESUMEN
Bi-manual therapy (BT), mirror therapy (MT), and robot-assisted rehabilitation have been conducted in hand training in a wide range of stages in stroke patients; however, the mechanisms of action during training remain unclear. In the present study, participants performed hand tasks under different intervention conditions to study bilateral sensorimotor cortical communication, and EEG was recorded. A multifactorial design of the experiment was used with the factors of manipulating objects (O), robot-assisted bimanual training (RT), and MT. The sum of spectral coherence was applied to analyze the C3 and C4 signals to measure the level of bilateral corticocortical communication. We included stroke patients with onset <6 months (n = 6), between 6 months and 1 year (n = 14), and onset >1 year (n = 20), and their Brunnstrom recovery stage ranged from 2 to 4. The results showed that stroke duration might influence the effects of hand rehabilitation in bilateral cortical corticocortical communication with significant main effects under different conditions in the alpha and beta bands. Therefore, stroke duration may influence the effects of hand rehabilitation on interhemispheric coherence.
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Study Design: A randomized controlled pilot study. Background: Bimanual therapy (BMT) is an effective neurorehabilitation therapy for the upper limb, but its application to the distal upper limb is limited due to methodological difficulties. Therefore, we applied an exoskeleton hand to perform robot-assisted task-oriented bimanual training (RBMT) in patients with stroke. Objective: To characterize the effectiveness of RBMT in patients with hemiplegic stroke with upper limb motor impairment. Interventions: A total of 19 patients with subacute stroke (1-6 months from onset) were randomized and allocated to RBMT and conventional therapy (CT) groups. The RBMT and CT groups received 90 min of training/day (RBMT: 60 min RBMT + 30 min CT; CT: 60 min CT for hand functional training + 30 min regular CT), 5 days/week, for 4 weeks (20 sessions during the experimental period). Assessments: Clinical assessments, including the Fugl-Meyer assessment of the upper extremity (FMA-UE), action research arm test (ARAT), and wolf motor arm function test (WMFT), were conducted before and after the intervention. Results: Within-group analysis showed a significant improvement in the FMA-UE and WMFT in both the CT and RBMT groups. A significant improvement in the Fugl-Meyer assessment (FMA) of the wrist and hand for the distal part in the RBMT group occurred earlier than that in the CT group. A significant improvement in WMFT time was found in both groups, but the WMFT functional ability assessment was only found in the RBMT group. No significant improvements in ARAT assessment were observed in either the CT or RBMT groups. Compared with CT, significant improvements were found in terms of the proportion of minimally clinically important differences after RBMT in FMA-UE (χ2 = 4.34, p = 0.037). No adverse events were reported by any of the participants across all sessions. Conclusions: This study is the first to apply RBMT to the distal part of the upper limb. Both RBMT and CT are effective in improving the upper limb function in patients with subacute stroke. RBMT shows superior potential efficacy in facilitating recovery of the distal part of upper extremity (UE) motor function in the early stage. Future randomized control studies with a large sample size and follow-up assessments are needed to validate the present conclusions.
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Paired stimulation has been applied to modulate neuronal functions in the primary somatosensory cortex but its utility in the alternation of tuning function, such as direction tuning for whisker stimuli, remains unclear. In the present study, we attempted to manipulate feature preferences in barrel cortical neurons using repetitive paired whisker deflection combined with optogenetic stimulation and to obtain optimal parameters that can induce neuroplasticity. We found no significant response changes across stimulus parameters, such as onset asynchronies and paired directions. Only when paired stimulation was applied in the nonpreferred direction of the principal whisker of a neuron, were the neuron's responses enhanced in that direction. Importantly, this effect was only observed when the optogenetic stimulus preceded the mechanical stimulus. Our findings indicate that repetitive paired optogenetic-mechanical stimulation can induce in vivo neuroplasticity of feature selectivity in limited situations.
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Optogenética , Vibrisas , Animales , Plasticidad Neuronal , Neuronas , Estimulación Física , Corteza SomatosensorialRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The hand explores the environment for obtaining tactile information that can be fruitfully integrated with other functions, such as vision, audition, and movement. In theory, somatosensory signals gathered by the hand are accurately mapped in the world-centered (allocentric) reference frame such that the multi-modal information signals, whether visual-tactile or motor-tactile, are perfectly aligned. However, an accumulating body of evidence indicates that the perceived tactile orientation or direction is inaccurate; yielding a surprisingly large perceptual bias. To investigate such perceptual bias, this study presented tactile motion stimuli to healthy adult participants in a variety of finger and head postures, and requested the participants to report the perceived direction of motion mapped on a video screen placed on the frontoparallel plane in front of the eyes. Experimental results showed that the perceptual bias could be divided into systematic and nonsystematic biases. Systematic bias, defined as the mean difference between the perceived and veridical directions, correlated linearly with the relative posture between the finger and the head. By contrast, nonsystematic bias, defined as minor difference in bias for different stimulus directions, was highly individualized, phase-locked to stimulus orientation presented on the skin. Overall, the present findings on systematic bias indicate that the transformation bias among the reference frames is dominated by the finger-to-head posture. Moreover, the highly individualized nature of nonsystematic bias reflects how information is obtained by the orientation-selective units in the S1 cortex.
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Percepción de Movimiento/fisiología , Postura/fisiología , Percepción del Tacto/fisiología , Adulto , Sesgo , Femenino , Dedos , Cabeza , Humanos , Masculino , Modelos Biológicos , Estimulación Luminosa , Estimulación FísicaRESUMEN
Psychophysical visual experiments have shown illusory motion reversal (IMR), in which the perceived direction of motion is the opposite of its actual direction. The tactile form of this illusion has also been reported. However, it remains unclear which stimulus characteristics affect the magnitude of IMR. We closely examined the effect of stimulus characteristics on IMR by presenting moving sinusoid gratings and random-dot patterns to 10 participants' fingerpads at different spatial periods, speeds, and indentation depths. All participants perceived a motion direction opposite to the veridical direction some of the time. The illusion was more prevalent at spatial periods of 1 and 2 mm and at extreme speeds of 20 and 320 mm/s. We observed stronger IMR for gratings and much weaker IMR for a random-dot pattern, indicating that edge orientation might be a major contributor to this illusion. These results show that the optimal parameters for IMR are consistent with the characteristics of motion-selective neurons in the somatosensory cortex, as most of these neurons are also orientation-selective. We speculate that these neurons could be the neural substrate that accounts for tactile IMR.
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BACKGROUND: Nerve reconstructive surgery induces a transient loss and a prolonged and a gradual return of sensory inputs to the brain. It is unknown whether, following this massive peripheral denervation, the brain will experience a prolonged period of severe, intrinsic dysfunction. OBJECTIVE: We aim to investigate the mechanisms of return of processing function in cortical neurons. METHODS: We used the whisker model in rats to evaluate the functional recovery in the somatosensory cortex after a nerve reconstruction surgery. Multi-unit recording in the barrel cortex was performed in lightly anesthetized rats while their whiskers were stimulated by a whisker stimulator. RESULTS: We observed a loss of neuronal responses to whisker stimulation 1 week after surgery, which started to recover 2 weeks after surgery. Following the surgery, only 11.8% of units had principle whiskers (PWs) returned to their original status while 17.7% had PWs different from their original status, indicating the effect of aberrant reinnervation on the whisker response map. CONCLUSIONS: Robust neuronal responses to sensory stimulation even when only sparse sensory inputs are available in the early recovery phase. During this phase, aberrant reinnervation induces disorganized whisker tuning, a finding that might be account for the hypoesthesia and paresthesia during early recovery after nerve reconstruction.
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Nervio Maxilar/fisiopatología , Procedimientos de Cirugía Plástica , Recuperación de la Función/fisiología , Corteza Somatosensorial/fisiopatología , Vibrisas/inervación , Vibrisas/fisiología , Animales , Estimulación Física , RatasRESUMEN
Study design: Case series. Background: Robot-assisted rehabilitation mediated by exoskeletal devices is a popular topic of research. The biggest difficulty in the development of rehabilitation robots is the consideration of the clinical needs. This study investigated the usability of a novel cable-driven exoskeletal robot specifically designed for hand rehabilitation. Methods: The study consists of three steps, including prototype development, spasticity observation, and usability evaluation. First, we developed the prototype robot DexoHand to manipulate the patient's fingers based on the clinical needs and the cable-driven concept established in our previous work. Second, we applied DexoHand to patients with different levels of spasticity. Finally, we obtained the system usability scale (SUS) and assessed its usability. Results: Two healthy subjects were recruited in the pre-test, and 18 patients with stroke and four healthy subjects were recruited in the formal test for usability. The total SUS score obtained from the patients and healthy subjects was 94.77 ± 2.98 (n = 22), indicating an excellent level of usability. The satisfaction score was 4.74 ± 0.29 (n = 22), revealing high satisfaction with DexoHand. The tension profile measured by the cables showed the instantaneous force used to manipulate fingers among different muscle tone groups. Conclusions: DexoHand meets the clinical needs with excellent usability, satisfaction, and reliable tension force monitoring, yielding a feasible platform for robot-assisted hand rehabilitation.
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OBJECTIVE: Nerve injury is the main reason for nerve reconstruction surgery, during which the surgeon must determine the location of the injured nerve segment, resect it, and reconnect the remaining healthy nerve stump ends within a limited time. Given this importance, an assay needed to determine the exact location of the injured nerve segment, but no tool has yet fulfilled this need so that a visual inspection of the nerve is still the primary method of identifying the injured segment. APPROACH: We designed a flexible multi-electrode array sensor that records the electroneurographic signal (ENG) as the action potential elicited by electrical stimulation that propagates along the nerve upon both orthodromic and antidromic stimulation. Its utility was validated by in vivo experiments in injured sciatic nerves of rats. MAIN RESULTS: The results showed that the first post stimulus negative electroneurographic component (N1) is the most valid neural correlate, as its amplitude decreased, and latency increased as the action potential propagated across the injured segment. Gradual recovery of nerve conduction was observed when measured immediately, 7, and 30 d after injury. The locations of the identified injured segments were validated by histological findings. SIGNIFICANCE: The sensor and the algorithm developed in this study are breakthroughs in surgical nerve assessment accomplished by determining the specific nerve segment that should be resected, enabling the optimal surgical outcome.
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Potenciales de Acción/fisiología , Monitorización Neurofisiológica Intraoperatoria/métodos , Conducción Nerviosa/fisiología , Nervio Ciático/lesiones , Nervio Ciático/fisiología , Animales , Estimulación Eléctrica/instrumentación , Estimulación Eléctrica/métodos , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Masculino , Microelectrodos , Ratas , Ratas Sprague-Dawley , Nervio Ciático/cirugíaRESUMEN
Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1. We also hypothesized that the suppression of burst firing in VPL using Z944, a novel T-type calcium channel blocker, restores S1 synchrony and thalamocortical connectivity. Local field potentials were recorded from S1 and VPL in anesthetized rats 7 days after sciatic chronic constriction injury (CCI). In rats with CCI, low-frequency (4-12 Hz) synchrony in S1 was enhanced, whereas VPL-S1 coherence and theta-gamma phase-amplitude coupling were attenuated. Moreover, Granger causality showed decreased informational flow from VPL to S1. Systemic or intrathalamic delivery of Z944 to rats with CCI normalized these changes. Systemic Z944 also reversed thermal hyperalgesia and conditioned place preference. These data suggest that pain-induced cortical synchrony and thalamocortical disconnectivity are directly related to burst firing in VPL.
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Acetamidas/farmacología , Benzamidas/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Corteza Cerebral/efectos de los fármacos , Neuralgia/fisiopatología , Tálamo/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Canales de Calcio Tipo T , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Piperidinas , Ratas , Ratas Sprague-Dawley , Tálamo/fisiopatologíaRESUMEN
Neural responses to sensory inputs caused by self-generated movements (reafference) and external passive stimulation (exafference) differ in various brain regions. The ability to differentiate such sensory information can lead to movement execution with better accuracy. However, how sensory responses are adjusted in regard to this distinguishability during motor learning is still poorly understood. The cerebellum has been hypothesized to analyze the functional significance of sensory information during motor learning, and is thought to be a key region of reafference computation in the vestibular system. In this study, we investigated Purkinje cell (PC) spike trains as cerebellar cortical output when rats learned to balance on a suspended dowel. Rats progressively reduced the amplitude of body swing and made fewer foot slips during a 5-min balancing task. Both PC simple (SSs; 17 of 26) and complex spikes (CSs; 7 of 12) were found to code initially on the angle of the heads with respect to a fixed reference. Using periods with comparable degrees of movement, we found that such SS coding of information in most PCs (10 of 17) decreased rapidly during balance learning. In response to unexpected perturbations and under anesthesia, SS coding capability of these PCs recovered. By plotting SS and CS firing frequencies over 15-s time windows in double-logarithmic plots, a negative correlation between SS and CS was found in awake, but not anesthetized, rats. PCs with prominent SS coding attenuation during motor learning showed weaker SS-CS correlation. Hence, we demonstrate that neural plasticity for filtering out sensory reafference from active motion occurs in the cerebellar cortex in rats during balance learning. SS-CS interaction may contribute to this rapid plasticity as a form of receptive field plasticity in the cerebellar cortex between two receptive maps of sensory inputs from the external world and of efference copies from the will center for volitional movements.
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Granger causality (GC) analysis has emerged as a powerful analytical method for estimating the causal relationship among various types of neural activity data. However, two problems remain not very clear and further researches are needed: (1) The GC measure is designed to be nonnegative in its original form, lacking of the trait for differentiating the effects of excitations and inhibitions between neurons. (2) How is the estimated causality related to the underlying synaptic weights? Based on the GC, we propose a computational algorithm under a best linear predictor assumption for analyzing neuronal networks by estimating the synaptic weights among them. Under this assumption, the GC analysis can be extended to measure both excitatory and inhibitory effects between neurons. The method was examined by three sorts of simulated networks: those with linear, almost linear, and nonlinear network structures. The method was also illustrated to analyze real spike train data from the anterior cingulate cortex (ACC) and the striatum (STR). The results showed, under the quinpirole administration, the significant existence of excitatory effects inside the ACC, excitatory effects from the ACC to the STR, and inhibitory effects inside the STR.
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Redes Neurales de la Computación , Sinapsis/fisiología , Potenciales de Acción , Algoritmos , Causalidad , Simulación por Computador , Cuerpo Estriado/citología , Cuerpo Estriado/fisiología , Fenómenos Electrofisiológicos , Giro del Cíngulo/citología , Giro del Cíngulo/fisiología , Humanos , Modelos Lineales , Modelos Neurológicos , Dinámicas no LinealesRESUMEN
Axon collateral projections to various lobules of the cerebellar cortex are thought to contribute to the coordination of neuronal activities among different parts of the cerebellum. Even though lobules I/II and IX/X of the cerebellar vermis are located at the opposite poles in the anterior-posterior axis, they have been shown to receive dense vestibular mossy fiber projections. For climbing fibers, there is also a mirror-image-like organisation in their axonal collaterals between the anterior and posterior cerebellar cortex. However, the detailed organisation of mossy and climbing fiber collateral afferents to lobules I/II and IX/X is still unclear. Here, we carried out a double-labeling study with two retrograde tracers (FluoroGold and MicroRuby) in lobules I/II and IX/X. We examined labeled cells in the vestibular nuclei and inferior olive. We found a low percentage of double-labeled neurons in the vestibular nuclei (2.1 ± 0.9% of tracer-labeled neurons in this brain region), and a higher percentage of double-labeled neurons in the inferior olive (6.5 ± 1.9%), especially in its four small nuclei (18.5 ± 8.0%; including the ß nucleus, dorsal cap of Kooy, ventrolateral outgrowth, and dorsomedial cell column), which are relevant for vestibular function. These results provide strong anatomical evidence for coordinated information processing in lobules I/II and IX/X for vestibular control.
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Vermis Cerebeloso/anatomía & histología , Neuronas/citología , Núcleo Olivar/anatomía & histología , Núcleos Vestibulares/anatomía & histología , Animales , Femenino , Vías Nerviosas/anatomía & histología , Técnicas de Trazados de Vías Neuroanatómicas , Fotomicrografía , Ratas Long-EvansRESUMEN
Neuronal oscillations have been shown to contribute to the function of the cerebral cortex by coordinating the neuronal activities of distant cortical regions via a temporal synchronization of neuronal discharge patterns. This can occur regardless whether these regions are linked by cortico-cortical pathways or not. Less is known concerning the role of neuronal oscillations in the cerebellum. Golgi cells and Purkinje cells are both principal cell types in the cerebellum. Purkinje cells are the sole output cells of the cerebellar cortex while Golgi cells contribute to information processing at the input stage of the cerebellar cortex. Both cell types have large cell bodies, as well as dendritic structures, that can generate large currents. The discharge patterns of both these cell types also exhibit oscillations. In view of the massive afferent information conveyed by the mossy fiber-granule cell system to different and distant areas of the cerebellar cortex, it is relevant to inquire the role of cerebellar neuronal oscillations in information processing. In this study, we compared the discharge patterns of Golgi cells and Purkinje cells in conscious rats and in rats anesthetized with urethane. We assessed neuronal oscillations by analyzing the regularity in the timing of individual spikes within a spike train by using autocorrelograms and fast-Fourier transform. We measured the differences in neuronal oscillations and the amount of information content in a spike train (defined by Shannon entropy processed per unit time) in rats under anesthesia and in conscious, awake rats. Our findings indicated that anesthesia caused more prominent neuronal oscillations in both Golgi cells and Purkinje cells accompanied by decreases in Shannon information entropy in their spike trains.
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Cerebelo/fisiología , Interneuronas/fisiología , Células de Purkinje/fisiología , Potenciales de Acción/efectos de los fármacos , Anestesia , Anestésicos Intravenosos/farmacología , Animales , Cerebelo/efectos de los fármacos , Estado de Conciencia/efectos de los fármacos , Estado de Conciencia/fisiología , Femenino , Análisis de Fourier , Teoría de la Información , Interneuronas/efectos de los fármacos , Locomoción/fisiología , Células de Purkinje/efectos de los fármacos , Ratas , Ratas Long-Evans , Factores de Tiempo , Uretano/farmacologíaRESUMEN
Efficient nanotextured black silicon solar cells passivated by an Al2O3 layer are demonstrated. The broadband antireflection of the nanotextured black silicon solar cells was provided by fabricating vertically aligned silicon nanowire (SiNW) arrays on the n(+) emitter. A highly conformal Al2O3 layer was deposited upon the SiNW arrays by the thermal atomic layer deposition (ALD) based on the multiple pulses scheme. The nanotextured black silicon wafer covered with the Al2O3 layer exhibited a low total reflectance of â¼1.5% in a broad spectrum from 400 to 800 nm. The Al2O3 passivation layer also contributes to the suppressed surface recombination, which was explored in terms of the chemical and field-effect passivation effects. An 8% increment of short-circuit current density and 10.3% enhancement of efficiency were achieved due to the ALD Al2O3 surface passivation and forming gas annealing. A high efficiency up to 18.2% was realized in the ALD Al2O3-passivated nanotextured black silicon solar cells.
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RATIONALE: The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized. However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex (ACC) and striatum (STR), two crucial regions for cognitive and motor functions, after quinpirole administration. OBJECTIVE: This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration. METHODS: Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane-anesthetized rats after administration of saline or 0.05 or 0.5 mg/kg quinpirole. RESULTS: In contrast to the responses to saline, quinpirole dose-dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR. By examining the ensemble neuronal activities of inhibition-responded neurons, there was no significant activity difference among the "treatments" (saline and low- and high-dose quinpirole), the "periods" (the duration of 0-15 and 16-45 min after i.v. injection), and the interaction between "treatments" and "periods." Regarding activation-responded neurons, however, there was a significant "periods" difference in both ACC and STR, and the activity of 16-45 min was significantly higher than the activity of 0-15 min after high-dose quinpirole administration in ACC (p < 0.05) and STR (p < 0.001). CONCLUSION: Dose-dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats. The late excitatory effect of high-dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity.
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Cuerpo Estriado/efectos de los fármacos , Agonistas de Dopamina/farmacología , Giro del Cíngulo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Quinpirol/farmacología , Receptores de Dopamina D2/agonistas , Animales , Cuerpo Estriado/fisiología , Relación Dosis-Respuesta a Droga , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Giro del Cíngulo/fisiología , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Masculino , Actividad Motora/fisiología , Neuronas/fisiología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND: Alcohol is a widely abused substance and is responsible for significant morbidity and mortality worldwide. The precise mechanisms underlying ethanol (EtOH)'s actions in the central nervous system (CNS) remain elusive. In vitro studies suggest that GABAergic interneurons are important targets of EtOH action in the CNS. Although EtOH generally acts to inhibit CNS neurons, it appears to cause an increase in GABAergic interneuron excitability. However, it has yet to be demonstrated that EtOH produces this effect in the brain of behaving animals. Here, we demonstrate for the first time that acute EtOH exposure excites a subtype of GABAergic interneuron (cerebellar Golgi cell [GoC]) in a freely moving animal. METHODS: Electrophysiological recordings were made from microwire arrays implanted in the anterior cerebellum of freely moving rats. RESULTS: Cerebellar GoCs display a slow, irregular, spontaneous action potential firing pattern under control conditions. EtOH caused dramatic and consistent increases in the rate and regularity of GoC discharges, including a redistribution of the power in the GoC spike train, such that power became concentrated in the 26.7 ± 7.3 Hz region. CONCLUSIONS: Taken together with our previous findings, these data suggest that a major mechanism of EtOH actions on cerebellar function is an EtOH-induced de-afferentation at the input stage of the cerebellar cortex in the form of granule cell inhibition, and that this inhibition is caused by an increase in GoC firing. It is likely that GoCs may play a significant role both in the gating of information transmission to granule cells and in the modulation of the overall excitability of the cerebellum by tonically controlling granule cell activity.