RESUMEN
Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.
Asunto(s)
Corteza Cerebral/fisiología , Neuronas/fisiología , Estimulación Acústica , Adulto , Animales , Estimulación Eléctrica , Electroencefalografía , Fenómenos Electrofisiológicos , Epilepsia/fisiopatología , Espacio Extracelular/fisiología , Femenino , Humanos , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microelectrodos , Persona de Mediana Edad , Corteza Somatosensorial/fisiología , Análisis de Ondículas , Adulto JovenRESUMEN
The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility in scalable and human-compatible implantable neural interfaces can significantly advance the performance of clinical and research electrodes. We utilize low-temperature selective dealloying to develop scalable and biocompatible one-dimensional platinum nanorod (PtNR) arrays that exhibit superb electrochemical properties at various length scales, stability, and biocompatibility for high performance neurotechnologies. PtNR arrays record brain activity with cellular resolution from the cortical surfaces in birds and nonhuman primates. Significantly, strong modulation of surface recorded single unit activity by auditory stimuli is demonstrated in European Starling birds as well as the modulation of local field potentials in the visual cortex by light stimuli in a nonhuman primate and responses to electrical stimulation in mice. PtNRs record behaviorally and physiologically relevant neuronal dynamics from the surface of the brain with high spatiotemporal resolution, which paves the way for less invasive brain-machine interfaces.
Asunto(s)
Potenciales de Acción , Materiales Biocompatibles , Interfaces Cerebro-Computador , Nanotubos , Neuronas/metabolismo , Platino (Metal) , Corteza Visual/fisiología , Animales , Estimulación Eléctrica , Electrodos , Macaca mulatta , Masculino , Ratones , Pájaros CantoresRESUMEN
Retinal implants have been developed as a promising way to restore partial vision for the blind. The observation and analysis of neural activities can offer valuable insights for successful prosthetic electrical stimulation. Retinal ganglion cell (RGC) activities have been investigated to provide knowledge on the requirements for electrical stimulation, such as threshold current and the effect of stimulation waveforms. To develop a detailed 'stimulation strategy' for faithful delivery of spatiotemporal visual information to the brain, it is essential to examine both the temporal and spatial characteristics of RGC responses, whereas previous studies were mainly focused on one or the other. In this study, we investigate whether the spatiotemporal visual information can be decoded from the RGC network activity evoked by patterned electrical stimulation. Along with a thorough characterization of spatial spreading of stimulation current and temporal information encoding, we demonstrated that multipixel spatiotemporal visual information can be accurately decoded from the population activities of RGCs stimulated by amplitude-modulated pulse trains. We also found that the details of stimulation, such as pulse amplitude range and pulse rate, were crucial for accurate decoding. Overall, the results suggest that useful visual function may be restored by amplitude modulation-based retinal stimulation.
Asunto(s)
Estimulación Eléctrica , Células Ganglionares de la Retina/fisiología , Animales , Potenciales Evocados Visuales/fisiología , Ratones , Microelectrodos , Prótesis e Implantes , Retina/trasplante , Análisis Espacio-TemporalRESUMEN
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.
RESUMEN
Micro-coil magnetic stimulation of brain tissue presents new challenges for MEMS micro-coil probe fabrication. The main challenges are threefold; (i) low coil resistance for high power efficiency, (ii) low leak current from the probe into the in vitro experimental set-up, (iii) adaptive MEMS process technology because of the dynamic research area, which requires agile design changes. Taking on these challenges, we present a MEMS fabrication process that has three main features; (i) multilayer resist lift-off process to pattern up to 1800-nm-thick metal films, and special care is taken to obtain high conductivity thin-films by physical vapor deposition, and (ii) all micro-coil Al wires are encapsulated in at least 200 nm of ALD alumina and 6-µm-thick parylene C such the leak resistance is high (>210 GΩ), (iii) combining a multi-step DRIE process and maskless photolithography for adaptive design and device fabrication. The entire process requires four lithography steps. Because we avoided SOI wafers and lithography mask fabrication, the design-to-device time is shortened significantly. The resulting probes are 4-mm-long, 60-µm-thick, and down to 150 µm-wide. Selected MEMS coil devices were validated in vivo using mice and compared to previous work.
Asunto(s)
Técnicas Biosensibles , Sistemas Microelectromecánicos , Animales , Ratones , Metales , Encéfalo , Conductividad EléctricaRESUMEN
This paper presents a novel sensing configuration for retinal physiology analysis, using two microelectrode arrays (MEAs). In order to investigate an optimized stimulation protocol for a sub-retinal prosthesis, retinal photoreceptor cells are stimulated, and the response of retinal ganglion cells is recorded in an in vitro environment. For photoreceptor cell stimulation, a polyimide-substrate MEA is developed, using the microelectromechanical systems (MEMS) technology. For ganglion cell response recording, a conventional glass-substrate MEA is utilized. This new sensing configuration is used to record the response of retinal ganglion cells with respect to three different stimulation methods (monopolar, bipolar, and dual-monopolar stimulation methods). Results show that the geometrical relation between the stimulation microelectrode locations and the response locations seems very low. The threshold charges of the bipolar stimulation and the monopolar stimulation are in the range of 10~20 nC. The threshold charge of the dual-monopolar stimulation is not obvious. These results provide useful guidelines for developing a sub-retinal prosthesis.
Asunto(s)
Retina/fisiología , Animales , Microelectrodos , Conejos , Prótesis VisualesRESUMEN
OBJECTIVE: Electrical stimulation via microelectrodes implanted in cortex has been suggested as a potential treatment for a wide range of neurological disorders. Despite some success however, the effectiveness of conventional electrodes remains limited, in part due to an inability to create specific patterns of neural activity around each electrode and in part due to challenges with maintaining a stable interface. The use of implantable micro-coils to magnetically stimulate the cortex has the potential to overcome these limitations because the asymmetric fields from coils can be harnessed to selectively activate some neurons, e.g. vertically-oriented pyramidal neurons while avoiding others, e.g. horizontally-oriented passing axons. In vitro experiments have shown that activation is indeed confined with micro-coils but their effectiveness in the intact brain of living animals has not been evaluated. APPROACH: To assess the efficacy of stimulation, a 128-channel custom recording microelectrode array was positioned on the surface of the visual cortex (ECoG) in anesthetized mice and responses to magnetic and electric stimulation were compared. Stimulation was delivered from electrodes or micro-coils implanted through a hole in the center of the recording array at a rate of 200 pulses per second for 100 ms. MAIN RESULTS: Both electric and magnetic stimulation reliably elicited cortical responses, although activation from electric stimulation was spatially expansive, often extending more than 1 mm from the stimulation site, while activation from magnetic stimulation was typically confined to a â¼300 µm diameter region around the stimulation site. Results were consistent for stimulation of both cortical layer 2/3 and layer 5 as well as across a range of stimulus strengths. SIGNIFICANCE: The improved focality with magnetic stimulation suggests that the effectiveness of cortical stimulation can be improved. Improved focality may be particularly attractive for cortical prostheses that require high spatial resolution, e.g. devices that target sensory cortex, as it may lead to improved acuity.
Asunto(s)
Corteza Visual , Animales , Estimulación Eléctrica , Electrodos Implantados , Fenómenos Magnéticos , Ratones , Microelectrodos , NeuronasRESUMEN
Retinal prostheses strive to restore vision to the blind by electrically stimulating the neurons that survive the disease process. Clinical effectiveness has been limited however, and much ongoing effort is devoted toward the development of improved stimulation strategies, especially ones that better replicate physiological patterns of neural signaling. Here, to better understand the potential effectiveness of different stimulation strategies, we explore the responses of neurons in the primary visual cortex to electric stimulation of the retina. A 16-channel implantable microprobe was used to record single unit activities in vivo from each layer of the mouse visual cortex. Layers were identified by electrode depth as well as spontaneous rate. Cell types were classified as excitatory or inhibitory based on their spike waveform and as ON, OFF, or ON-OFF based on the polarity of their light response. After classification, electric stimulation was delivered via a wire electrode placed on the surface of cornea (extraocularly) and responses were recorded from the cortex contralateral to the stimulated eye. Responses to electric stimulation were highly similar across cell types and layers. Responses (spike counts) increased as a function of the amplitude of stimulation, and although there was some variance across cells, the sensitivity to amplitude was largely similar across all cell types. Suppression of responses was observed for pulse rates ≥3 pulses per second (PPS) but did not originate in the retina as RGC responses remained stable to rates up to 5 PPS. Low-frequency sinusoids delivered to the retina replicated the out-of-phase responses that occur naturally in ON vs. OFF RGCs. Intriguingly, out-of-phase signaling persisted in V1 neurons, suggesting key aspects of neural signaling are preserved during transmission along visual pathways. Our results describe an approach to evaluate responses of cortical neurons to electric stimulation of the retina. By examining the responses of single cells, we were able to show that some retinal stimulation strategies can indeed better match the neural signaling patterns used by the healthy visual system. Because cortical signaling is better correlated to psychophysical percepts, the ability to evaluate which strategies produce physiological-like cortical responses may help to facilitate better clinical outcomes.
RESUMEN
Retinal implants offered the promise of restoring functional vision to the blind via the delivery of electrical stimulation to the retina. To enhance the efficacy of these devices, stimulation should elicit neural responses that are similar to the responses that occur naturally in the retina as these have the best chance of carrying a robust signal to visual cortex. A corollary of this is that the responses that arise in visual cortical neurons can be used to compare the effectiveness of different stimulation strategies in the retina. Here, we studied how visual cortical neurons in the mouse respond to monophasic cathodal and anodal electric stimulation delivered via a wire electrode positioned on the outer surface of the eye (extraocular) or within the vitreous cavity of the eye (intraocular). Responses of visual cortical neurons were recorded from primary visual cortex on the side contralateral to the stimulatated eye. For both stimulation modalities, response patterns consisted of a brief burst of spikes followed by a 400-500 ms period of inhibition. Both modalities also elicited stronger responses to cathodal stimuli (vs. anodal). The preferential sensitivity to cathodal stimuli is similar to that of epiretinal stimulation (anodal stimuli are more effective with sub-retinal stimulation) suggest the extraocular approach mirrors epiretinal stimulation. Extraocular stimulation also showed some response characteristics that were different from those observed in the retina, e.g., at very strong amplitudes, cathodal and anodal stimulation produced similar responses.
Asunto(s)
Corteza Visual , Animales , Estimulación Eléctrica , Potenciales Evocados Visuales , Ratones , Neuronas , RetinaRESUMEN
OBJECTIVE: Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. METHODS: Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. RESULTS: MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. CONCLUSIONS: This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.
Asunto(s)
Estimulación Encefálica Profunda , Corteza Motora , Neuralgia/etiología , Neuralgia/terapia , Transducción de Señal/fisiología , Animales , Modelos Animales de Enfermedad , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Núcleos Talámicos VentralesRESUMEN
Chronic monitoring of intravesical pressure is required to detect the onset of intravesical hypertension and the progression of a more severe condition. Recent reports demonstrate the bladder state can be monitored from the spiking activity of the dorsal root ganglia or lumbosacral spinal cord. However, one of the most serious challenges for these methods is the difficulty of sustained spike signal acquisition due to the high-electrode-location-sensitivity of spikes or neuro-degeneration. Alternatively, it has been demonstrated that local field potential recordings are less affected by encapsulation reactions or electrode location changes. Here, we hypothesized that local field potential (LFP) from the lumbosacral dorsal horn may provide information concerning the intravesical pressure. LFP and spike activities were simultaneously recorded from the lumbosacral spinal cord of anesthetized rats during bladder filling. The results show that the LFP activities carry significant information about intravesical pressure along with spiking activities. Importantly, the intravesical pressure is decoded from the power in high-frequency bands (83.9-256 Hz) with a substantial performance similar to that of the spike train decoding. These findings demonstrate that high-frequency LFP activity can be an alternative intravesical pressure monitoring signal, which could lead to a proper closed loop system for urinary control.
Asunto(s)
Potenciales de Acción/fisiología , Región Lumbosacra/fisiología , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Médula Espinal/fisiología , Vejiga Urinaria/fisiología , Algoritmos , Anestesia , Animales , Electrodos , Femenino , Ganglios Espinales/fisiología , Prótesis Neurales , Presión , Ratas , Ratas Sprague-Dawley , Vejiga Urinaria/inervaciónRESUMEN
Retinal prostheses are being developed to restore vision for those with retinal diseases such as retinitis pigmentosa or age-related macular degeneration. Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. In this paper, we focused on retinal ganglion cell (RGC) responses to different stimulation parameters and compared threshold charge densities in wild-type and rd1 mice. For this purpose, we used in vitro retinal preparations of wild-type and rd1 mice. When the neural network was stimulated with voltage- and current-controlled pulses, RGCs from both wild-type and rd1 mice responded; however the temporal pattern of RGC response is very different. In wild-type RGCs, a single peak within 100 ms appears, while multiple peaks (approximately four peaks) with â¼ 10 Hz rhythm within 400 ms appear in RGCs in the degenerated retina of rd1 mice. We find that an anodic phase-first biphasic voltage-controlled pulse is more efficient for stimulation than a biphasic current-controlled pulse based on lower threshold charge density. The threshold charge densities for activation of RGCs both with voltage- and current-controlled pulses are overall more elevated for the rd1 mouse than the wild-type mouse. Here, we propose the stimulus range for wild-type and rd1 retinas when the optimal modulation of a RGC response is possible.
Asunto(s)
Potenciales de Acción , Estimulación Eléctrica/métodos , Células Ganglionares de la Retina , Retinitis Pigmentosa/fisiopatología , Animales , Células Cultivadas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6 , Ratones , Ratones Noqueados , Retinitis Pigmentosa/rehabilitaciónRESUMEN
PURPOSE: To restore visual function via the prosthetic stimulation of retina, visual information must be properly represented in the electrically evoked neural activity of retinal ganglion cells (RGCs). In this study, the RGC responses in photoreceptor-degenerated retinas were shown to actually encode temporal information on visual input when they were stimulated by biphasic pulse trains with amplitude modulation. METHODS: Multiple RGC spike trains were recorded from rd1 mouse retinal patches mounted on planar microelectrode arrays while being stimulated by pulse trains with amplitudes modulated by the intensity variation of a natural scene. To reconstruct the time series of pulse train amplitudes from the evoked RGC activity, spike train decoding was performed. The accuracy of decoding-that is, the similarity between the original and decoded pulse amplitudes-was observed, to evaluate the appropriateness of the stimulation. RESULTS: The response strengths of the RGCs could be successfully modulated when the pulse amplitude was varied between 2 and 20 µA. When the amplitude modulation range and pulse rates were determined elaborately, the temporal profile of the intensity could be successfully decoded from RGC spike trains, although abnormal oscillatory background rhythms (~10 Hz) were consistently present in the rd1 spike activity. CONCLUSIONS: The results extend previous findings on the possibility of visual information encoding by electrical stimulation of normal retinas to stimulate degenerated retinas, in which neural activity is significantly altered. This supports the feasibility of encoding of temporal information by retinal prostheses.
Asunto(s)
Potenciales Evocados Visuales/fisiología , Células Fotorreceptoras de Vertebrados/patología , Degeneración Retiniana/fisiopatología , Células Ganglionares de la Retina/fisiología , Animales , Modelos Animales de Enfermedad , Estimulación Eléctrica , Ratones , Ratones Endogámicos C3H , MicroelectrodosRESUMEN
Previously, we reported that besides retinal ganglion cell (RGC) spike, there is ~ 10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal degeneration model, rd1 mice. The more recently identified rd10 mice have a later onset and slower rate of photoreceptor degeneration than the rd1 mice, providing more therapeutic potential. In this study, before adapting rd10 mice as a new animal model for our electrical stimulation study, we investigated electrical characteristics of rd10 mice. From the raw waveform of recording using 8×8 microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP were isolated by using different filter setting. Fourier transform was performed for detection of frequency of bursting RGC spikes and oscillatory field potential (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always phase-locked with the OFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, there is a strong phase-locking tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first peak of OFP (~5 Hz) across different age groups. But this phase-locking property is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5 Hz), we expect different response patterns to electrical stimulus between rd1 and rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina, first we might define selection criteria for responding rd10 ganglion cells to electrical stimulus.
RESUMEN
Among the many animal models of retinitis pigmentosa (RP), the most extensively characterized animal is the rd1 mouse. Recent studies showed that the neurophysiological properties of rd1 retinas differ significantly from those of normal retina; the presence of an oscillatory rhythmic activity (~10 Hz) both in retinal ganglion cell (RGC) spikes and field potentials (slow wave component, SWC). However, lesser studies have been done regarding electrical characteristics of rd10 retina, carrying the mutation of same rod-PDE gene and showing a later onset degeneration of photoreceptors. Therefore, in this study, we compared the oscillatory rhythm in RGC spike and SWC between rd1 and rd10 mice in different postnatal ages to understand neural code used by two diseased retinas to communicate with the brain. Extracellular action potentials are recorded by 8 × 8 MEA from the RGC in the in vitro whole mount retina. 4 and 8 weeks in rd1 mice and 4, 10, 15, and 20 weeks in rd10 mice were used (n=3 for each postnatal age). From the raw waveform of retinal recording, RGC Spikes and SWC were isolated by using 200 Hz high-pass filter and 20 Hz low-pass filter, respectively. Fourier transform was performed for detection of oscillatory rhythm in RGC spikes and SWC. In rd1 mice, there is no statistical difference between the frequency of SWC and spike in 4 weeks [p>0.05; spike 9.3 ± 0.9 Hz (n=40), SWC 9.3 ± 1.5 Hz (n=25)] and 8 weeks [p>0.05; spike 10.0 ± 1.3 Hz (n=87), SWC 10.9 ± 1.7 Hz (n=25)]. While in rd10 mice there is no statistical differences among the SWC through 4 ~ 20 weeks, significant differences were observed between the frequency of RGC spike and SWC and also among RGC spikes [4 weeks (p<0.001): spike 5.5 ± 1.3 Hz (n=59), SWC 10.8 ± 3.1 Hz (n=14); 10 weeks (p<0.001): spike 6.8 ± 3.8 Hz (n=79), SWC 10.3 ± 2.6 Hz (n=25); 15 weeks (p<0.05): spike 3.9 ± 0.7 Hz (n=33), SWC 9.9 ± 1.2 Hz (n=25); 20 weeks (p<0.05): spike 4.4 ± 1.2 Hz (n=53), SWC 9.8 ± 1.2 Hz (n=25)].
Asunto(s)
Potenciales de Acción , Relojes Biológicos , Modelos Animales de Enfermedad , Células Ganglionares de la Retina , Retinitis Pigmentosa/fisiopatología , Animales , Ratones , Ratones Transgénicos , Especificidad de la EspecieRESUMEN
The purpose of this study was to identify consistent characteristic changes of neuronal activity in basal ganglia (BG) nuclei associated with Parkinson's disease (PD) so that a reliable index of PD can be derived. A simple algorithm for automatic identification of firing patterns was devised as an essential tool to achieve this goal. A detailed quantitative analysis of firing patterns as well as firing rate was performed in three BG nuclei: the subthalamic nucleus (STN), the substantia nigra pars reticulate (SNpr), and the globus pallidus (GP). The results showed that the firing rate of STN neurons was not significantly altered in PD model rats. We also did not find a significant alteration in firing rates in the SNpr and GP between normal and PD model rats. In contrast, consistent changes of firing patterns were observed in all three BG nuclei in that the percentage of neurons with a regular firing pattern decreased whereas those with irregular, mixed, or burst patterns increased. This enables a simple algorithm based on burst detection and the shape of the interspike interval histogram to identify whether the neuronal activity is from normal or PD model rats.
Asunto(s)
Potenciales de Acción/fisiología , Neuronas/fisiología , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/fisiopatología , Animales , Globo Pálido/patología , Globo Pálido/fisiopatología , Masculino , Neuronas/patología , Oxidopamina/toxicidad , Trastornos Parkinsonianos/diagnóstico , Ratas , Ratas Sprague-Dawley , Sustancia Negra/patología , Sustancia Negra/fisiopatología , Núcleo Subtalámico/patología , Núcleo Subtalámico/fisiopatologíaRESUMEN
Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. Therefore, in this paper, we focused on RGC responses to different stimulation parameters in degenerated retina. For this purpose, we used in vitro preparation of rd1 mice retina on microelectrode arrays. When the neural network of rd1 mice retinas is stimulated with voltage-controlled pulses, RGCs in degenerated retina also respond to voltage amplitude or voltage duration modulation as well in wild-type RGCs. But the temporal pattern of RGCs response is very different; in wild-type RGCs, single peak within 100 ms appears while in RGCs in degenerated retina multiple peaks (approximately 4 peaks) with approximately 10 Hz rhythm within 400 ms appear. The threshold charge densities for activation of RGCs in rd1 mouse retinas were on average 70.50 approximately 99.87 microC/cm(2) in the experiment of voltage amplitude modulation and 120.5 approxiamtely 170.6 microC/cm(2) in the experiment of voltage duration modulation.
Asunto(s)
Estimulación Eléctrica/métodos , Células Ganglionares de la Retina/fisiología , Prótesis Visuales , Animales , Impedancia Eléctrica , Ratones , Modelos TeóricosRESUMEN
PURPOSE: The electrophysiological properties of degenerated retinas responding to amplitude-modulated electrical pulse trains were investigated to provide a guideline for the development of a stimulation strategy for retinal prostheses. METHODS: The activities of retinal ganglion cells (RGCs) in response to amplitude-modulated pulse trains were recorded from an in vitro model of retinal prosthesis, which consisted of an rd1 mouse retinal patch attached to a planar multielectrode array. The ability of the population activities of RGCs to effectively represent, or encode, the information on the visual intensity time series, when the intensity of visual input is transformed to pulse amplitudes, was investigated. RESULTS: An optimal pulse amplitude range was selected so that RGC firing rates increased monotonically and linearly. An approximately 10-Hz rhythm was observed in the field potentials from degenerated retinas, which resulted in a rhythmic burst of spontaneous spikes. Multiple peaks were present in poststimulus time histograms, with interpeak intervals corresponding to the oscillation frequency of the field potentials. Phase resetting of the field potential oscillation by stimulation was consistently observed. Despite a prominent alteration of the properties of electrically evoked firing with respect to normal retinas, RGC response strengths could be modulated by pulse amplitude. Accordingly, the temporal information of stimulation could be faithfully represented in the RGC firing patterns by an amplitude-modulated pulse train. CONCLUSIONS: The results suggest that pulse amplitude modulation is a feasible means of implementing a stimulation strategy for retinal prostheses, despite the marked change in the physiological properties of RGCs in degenerated retinas.
Asunto(s)
Potenciales de Acción/fisiología , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Potenciales Evocados Visuales/fisiología , Degeneración Retiniana/fisiopatología , Células Ganglionares de la Retina/fisiología , Animales , Electrodos Implantados , Ratones , Ratones Endogámicos C3H , Umbral SensorialRESUMEN
For successful restoration of vision by retinal prostheses, the neural activity of retinal ganglion cells (RGCs) evoked by electrical stimulation should represent the information of spatiotemporal patterns of visual input. We propose a method to evaluate the effectiveness of stimulation pulse trains so that the crucial temporal information of a visual input is accurately represented in the RGC responses as the amplitudes of pulse trains are modulated according to the light intensity. This was enabled by spike train decoding. The effectiveness of the stimulation was evaluated by the accuracy of decoding pulse amplitude from the RGC spike train, i.e., by the similarity between the original and the decoded pulse amplitude time series. When the parameters of stimulation were suitably determined, the RGC responses were reliably modulated by varying the amplitude of electrical pulses. Accordingly, the temporal pattern of pulse amplitudes could be successfully decoded from multiunit RGC spike trains. The range of pulse amplitude and the pulse rate were critical for accurate representation of input information in RGC responses. These results suggest that pulse amplitude modulation is a feasible means to encode temporal visual information by RGC spike trains and thus to implement stimulus encoding strategies for retinal prostheses.
Asunto(s)
Potenciales de Acción/fisiología , Estimulación Eléctrica/métodos , Retina/citología , Células Ganglionares de la Retina/fisiología , Animales , Fenómenos Biofísicos/fisiología , Técnicas In Vitro , Masculino , ConejosRESUMEN
For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.