Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
CNS Neurosci Ther ; 25(8): 884-893, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30941924

RESUMO

AIM: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. METHODS: EHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation. RESULTS: The activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation. CONCLUSION: The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.

2.
Neurobiol Dis ; 129: 169-181, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30798003

RESUMO

Despite decades of research, our understanding of epilepsy, including how seizures are generated and propagate, is incomplete. However, there is growing recognition that epilepsy is more than just the occurrence of seizures, with patients often experiencing comorbid deficits in cognition that are poorly understood. In addition, the available therapies for treatment of epilepsy, from pharmaceutical treatment to surgical resection and seizure prevention devices, often exacerbate deficits in cognitive function. In this review, we discuss the hypothesis that seizure generation and cognitive deficits have a similar pathological source characterized by, but not limited to, deficits in theta oscillations and their influence on interneurons. We present a new framework that describes oscillatory states in epilepsy as alternating between hyper- and hypo-synchrony rather than solely the spontaneous transition to hyper-excitability characterized by the seizures. This framework suggests that as neural oscillations, specifically in the theta range, vary their tempo from a slowed almost adagio tempo during interictal periods to faster, more rhythmic allegretto tempo preictally, they impact the function of interneurons, modulating their ability to control seizures and their role in cognitive processing. This slow wave oscillatory framework may help explain why current therapies that work to reduce hyper-excitability do not completely eliminate seizures and often lead to exacerbated cognitive deficits.

3.
Neuroimage Clin ; 20: 398-406, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30128278

RESUMO

Background: Electrode contact locations are important when planning tailored brain surgeries to identify pathological tissue targeted for resection and conversely avoid eloquent tissue. Current methods employ trained experts to use neuroimaging scans that are manually co-registered and localize contacts within ~2 mm. Yet, the state of the art is limited by either the expertise needed for each type of intracranial electrode or the inter-modality co-registration which increases error, reducing accuracy. Patients often have a variety of strips, grids and depths implanted; therefore, it is cumbersome and time-consuming to apply separate localization methods for each type of electrode, requiring expertise across different approaches. New method: To overcome these limitations, a computational method was developed by separately registering an implant magnetic resonance image (MRI) and implant computed tomography image (CT) to the pre-implant MRI, then calculating an iterative closest point transformation using the contact locations extracted from the signal voids as ground truth. Results: The implant MRI is robustly co-registered to the pre-implant MRI with a boundary-based registration algorithm. By extracting and utilizing 'signal voids' (the metal induced artifacts from the implant MRI) as electrode fiducials, the novel method is an all-in-one approach for all types of intracranial electrodes while eliminating inter-modality co-registration errors. Comparison with existing methods: The distance between each electrode centroid and the brain's surface was measured, for the proposed method as well as the state of the art method using two available software packages, SPM 12 and FSL 4.1. The method presented here achieves the smallest distances to the brain's surface for all strip and grid type electrodes, i.e. contacts designed to rest directly on the brain surface. Conclusion: We use one of the largest reported sample sizes in localization studies to validate this novel method for localizing different kinds of intracranial electrodes including grids, strips and depth electrodes.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Eletrodos Implantados , Eletroencefalografia/métodos , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrodos Implantados/normas , Eletroencefalografia/instrumentação , Eletroencefalografia/normas , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/normas , Adulto Jovem
4.
J Neurosci Methods ; 306: 103-114, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859878

RESUMO

BACKGROUND: Most brain machine interfaces (BMI) focus on upper body function in non-injured animals, not addressing the lower limb functional needs of those with paraplegia. A need exists for a novel BMI task that engages the lower body and takes advantage of well-established rodent spinal cord injury (SCI) models to study methods to improve BMI performance. NEW METHOD: A tilt BMI task was designed that randomly applies different types of tilts to a platform, decodes the tilt type applied and rights the platform if the decoder correctly classifies the tilt type. The task was tested on female rats and is relatively natural such that it does not require the animal to learn a new skill. It is self-rewarding such that there is no need for additional rewards, eliminating food or water restriction, which can be especially hard on spinalized rats. Finally, task difficulty can be adjusted by making the tilt parameters. RESULTS: This novel BMI task bilaterally engages the cortex without visual feedback regarding limb position in space and animals learn to improve their performance both pre and post-SCI.Comparison with Existing Methods: Most BMI tasks primarily engage one hemisphere, are upper-body, rely heavily on visual feedback, do not perform investigations in animal models of SCI, and require nonnaturalistic extrinsic motivation such as water rewarding for performance improvement. Our task addresses these gaps. CONCLUSIONS: The BMI paradigm presented here will enable researchers to investigate the interaction of plasticity after SCI and plasticity during BMI training on performance.


Assuntos
Interfaces Cérebro-Computador , Neurônios/fisiologia , Paraplegia/fisiopatologia , Desempenho Psicomotor/fisiologia , Córtex Sensório-Motor/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Desenho de Equipamento , Feminino , Aprendizagem/fisiologia , Masculino , Paraplegia/reabilitação , Ratos Long-Evans , Traumatismos da Medula Espinal/reabilitação
5.
Exp Neurol ; 304: 132-142, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29526741

RESUMO

Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy. 5-HT, 5-HT2AR, 5-HT1AR, and dendritic densities were quantified both early (1 week) and late (9 weeks) after SCI, and also following therapeutic interventions (5-HT pharmacotherapy, bike therapy, or a combination). Interestingly, chronic 5-HT pharmacotherapy largely normalized spinal 5-HTR upregulation following injury. Improvement in locomotor behavior was not correlated to 5-HTR density. These results support the hypothesis that chronic 5-HT pharmacotherapy can mediate recovery following SCI, despite acting on largely normal spinal 5-HTR levels. We next assessed spinal dendritic plasticity and its potential role in locomotor recovery. Single therapies did not normalize the loss of dendritic density after SCI. Groups displaying significantly atrophied dendritic processes were rarely able to achieve weight supported open-field locomotion. Only a combination of 5-HT pharmacotherapy and bike therapy enabled significant open-field weigh-supported stepping, mediated in part by restoring spinal dendritic density. These results support the use of combined therapies to synergistically impact multiple markers of spinal plasticity and improve motor recovery.


Assuntos
Plasticidade Neuronal/fisiologia , Quipazina/farmacologia , Recuperação de Função Fisiológica/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Traumatismos da Medula Espinal/fisiopatologia , Envelhecimento , Animais , Feminino , Plasticidade Neuronal/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologia
6.
Epilepsia ; 59(3): 636-649, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29442363

RESUMO

OBJECTIVE: To gain understanding of the neuronal mechanisms underlying regional seizure spread, the impact of regional synchrony between seizure focus and downstream networks on neuronal activity during the transition to seizure in those downstream networks was assessed. METHODS: Seven patients undergoing diagnostic intracranial electroencephalographic studies for surgical resection of epileptogenic regions were implanted with subdural clinical electrodes into the cortex (site of seizure initiation) and mesial temporal lobe (MTL) structures (downstream) as well as microwires into MTL. Neural activity was recorded (24/7) in parallel with the clinical intracranial electroencephalogram recordings for the duration of the patient's diagnostic stay. Changes in (1) regional synchrony (ie, coherence) between the presumptive neocortical seizure focus and MTL, (2) local synchrony between MTL neurons and their local field potential, and (3) neuronal firing rates within MTL in the time leading up to seizure were examined to study the mechanisms underlying seizure spread. RESULTS: In seizures of neocortical origin, an increase in regional synchrony preceded the spread of seizures into MTL (predominantly hippocampal). Within frequencies similar to those of regional synchrony, MTL networks showed an increase in unit-field coherence and a decrease in neuronal firing rate, specifically for inhibitory interneuron populations but not pyramidal cell populations. SIGNIFICANCE: These results suggest a mechanism of spreading seizures whereby the seizure focus first synchronizes local field potentials in downstream networks to the seizure activity. This change in local field coherence modifies the activity of interneuron populations in these downstream networks, which leads to the attenuation of interneuronal firing rate, effectively shutting down local interneuron populations prior to the spread of seizure. Therefore, regional synchrony may influence the failure of downstream interneurons to prevent the spread of the seizures during generalization.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Neocórtex/fisiopatologia , Rede Nervosa/fisiopatologia , Neurônios/fisiologia , Convulsões/fisiopatologia , Adolescente , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Adulto Jovem
7.
J Neurosci ; 37(41): 10012-10021, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-28899918

RESUMO

Adaptation of neural responses due to the history of sensory input has been observed across all sensory modalities. However, the computational role of adaptation is not fully understood, especially when one considers neural coding problems in which adaptation increases the ambiguity of the neural responses to simple stimuli. To address this, we quantified the impact of adaptation on the information conveyed by thalamic neurons about paired whisker stimuli in male rat. At the single neuron level, although paired-pulse adaptation reduces the information about the present stimulus, the information per spike increases. Moreover, the adapted response can convey significant amounts of information about whether, when and where a previous stimulus occurred. At the population level, ambiguity of the adapted responses about the present stimulus can be compensated for by large numbers of neurons. Therefore, paired-pulse adaptation does not reduce the discriminability of simple stimuli. It provides information about the spatiotemporal context of stimulus history.SIGNIFICANCE STATEMENT The present work provides a computational framework that demonstrates how adaptation allows neurons to encode spatiotemporal dynamics of stimulus history.


Assuntos
Adaptação Fisiológica/fisiologia , Neurônios/fisiologia , Tálamo/fisiologia , Animais , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Percepção Espacial/fisiologia , Tálamo/citologia , Vibrissas/inervação , Vibrissas/fisiologia
8.
Elife ; 62017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28661400

RESUMO

After paralyzing spinal cord injury the adult nervous system has little ability to 'heal' spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury.


Assuntos
Membro Posterior/fisiologia , Córtex Motor/fisiologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Axônios/fisiologia , Locomoção , Ratos
9.
Front Neurosci ; 11: 715, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29311792

RESUMO

Single neuron and local field potential signals recorded in the primary motor cortex have been repeatedly demonstrated as viable control signals for multi-degree-of-freedom actuators. Although the primary source of these signals has been fore/upper limb motor regions, recent evidence suggests that neural adaptation underlying neuroprosthetic control is generalizable across cortex, including hindlimb sensorimotor cortex. Here, adult rats underwent a longitudinal study that included a hindlimb pedal press task in response to cues for specific durations, followed by brain machine interface (BMI) tasks in healthy rats, after rats received a complete spinal transection and after the BMI signal controls epidural stimulation (BMI-FES). Over the course of the transition from learned behavior to BMI task, fewer neurons were responsive after the cue, the proportion of neurons selective for press duration increased and these neurons carried more information. After a complete, mid-thoracic spinal lesion that completely severed both ascending and descending connections to the lower limbs, there was a reduction in task-responsive neurons followed by a reacquisition of task selectivity in recorded populations. This occurred due to a change in pattern of neuronal responses not simple changes in firing rate. Finally, during BMI-FES, additional information about the intended press duration was produced. This information was not dependent on the stimulation, which was the same for short and long duration presses during the early phase of stimulation, but instead was likely due to sensory feedback to sensorimotor cortex in response to movement along the trunk during the restored pedal press. This post-cue signal could be used as an error signal in a continuous decoder providing information about the position of the limb to optimally control a neuroprosthetic device.

10.
Exp Neurol ; 283(Pt A): 341-52, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27353968

RESUMO

Multiple studies have observed heterogeneous neuronal firing patterns as a local network transitions to spontaneous seizures. We demonstrated that separately examining interneurons and pyramidal cells during this transition in a rat model of temporal lobe epilepsy elucidates some of this heterogeneity. Recently, it was demonstrated that classifying cells into specific theta-related subtypes further clarified the heterogeneity. Moreover, changes in neuronal synchrony with the local field potential were identified and determined to be specific to interneurons during the transition to seizures. To extend our understanding of the chronic changes in epileptic networks, we examined field potentials and single neuron activity in the CA3 hippocampus of pilocarpine-treated rats during interictal periods and compared these to neuronal activity in healthy controls and during preictal periods. Neurons were classified into theta-subtypes based on changes in firing patterns during theta periods. As previously reported, we find a high probability of theta oscillations before seizure onset and a selective increase in theta-on interneuron firing rate immediately preceding seizure onset. However, we also find overall slower theta rhythm and a general decrease in subtype-specific firing during interictal periods compared to that in control animals. The decrease in subtype specific interneuron activity is accompanied by increases in synchrony. Exceptionally, theta-on interneurons, that selectively increase their firing rate at seizure onset, maintain similar firing rates and synchrony as controls during interictal period. These data suggest that increased synchrony during interictal periods may compensate for low firing rates creating instability during theta that is prone to seizure initiation via a transition to hyper-synchronous activation of theta-on interneurons.


Assuntos
Região CA3 Hipocampal/patologia , Região CA3 Hipocampal/fisiopatologia , Epilepsia/patologia , Interneurônios/fisiologia , Ritmo Teta/fisiologia , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Masculino , Movimento/fisiologia , Agonistas Muscarínicos/toxicidade , Pilocarpina/toxicidade , Ratos , Ratos Long-Evans , Estatísticas não Paramétricas , Ritmo Teta/efeitos dos fármacos
11.
Exp Neurol ; 279: 1-12, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26826448

RESUMO

Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost-effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury.


Assuntos
Córtex Motor/patologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Animais , Ciclismo , Vias Eferentes/patologia , Estimulação Elétrica , Terapia por Exercício , Feminino , Membro Posterior/inervação , Membro Posterior/fisiopatologia , Locomoção , Microeletrodos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Serotoninérgicos/uso terapêutico , Córtex Somatossensorial/patologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/tratamento farmacológico
12.
Neurorehabil Neural Repair ; 30(5): 479-89, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26338432

RESUMO

BACKGROUND: In rat models of spinal cord injury, at least 3 different strategies can be used to promote long-term cortical reorganization: (1) active exercise above the level of the lesion; (2) passive exercise below the level of the lesion; and (3) serotonergic pharmacotherapy. Whether and how these potential therapeutic strategies-and their underlying mechanisms of action-interact remains unknown. Methods In spinally transected adult rats, we compared the effects of active exercise above the level of the lesion (treadmill), passive exercise below the level of the lesion (bike), serotonergic pharmacotherapy (quipazine), and combinations of the above therapies (bike+quipazine, treadmill+quipazine, bike+treadmill+quipazine) on long-term cortical reorganization (9 weeks after the spinal transection). Cortical reorganization was measured as the percentage of cells recorded in the deafferented hindlimb cortex that responded to tactile stimulation of the contralateral forelimb. Results Bike and quipazine are "competing" therapies for cortical reorganization, in the sense that quipazine limits the cortical reorganization induced by bike, whereas treadmill and quipazine are "collaborative" therapies, in the sense that the reorganization induced by quipazine combined with treadmill is greater than the reorganization induced by either quipazine or treadmill. CONCLUSIONS: These results uncover the interactive effects between active/passive exercise and serotonergic pharmacotherapy on cortical reorganization after spinal cord injury, emphasizing the importance of understanding the effects of therapeutic strategies in spinal cord injury (and in other forms of deafferentation) from an integrated system-level approach.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Terapia por Exercício/métodos , Quipazina/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Traumatismos da Medula Espinal , Potenciais de Ação/efeitos dos fármacos , Análise de Variância , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Teste de Esforço , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação
13.
Neuron ; 86(1): 55-67, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25856486

RESUMO

The field of invasive brain-machine interfaces (BMIs) is typically associated with neuroprosthetic applications aiming to recover loss of motor function. However, BMIs also represent a powerful tool to address fundamental questions in neuroscience. The observed subjects of BMI experiments can also be considered as indirect observers of their own neurophysiological activity, and the relationship between observed neurons and (artificial) behavior can be genuinely causal rather than indirectly correlative. These two characteristics defy the classical object-observer duality, making BMIs particularly appealing for investigating how information is encoded and decoded by neural circuits in real time, how this coding changes with physiological learning and plasticity, and how it is altered in pathological conditions. Within neuroengineering, BMI is like a tree that opens its branches into many traditional engineering fields, but also extends deep roots into basic neuroscience beyond neuroprosthetics.


Assuntos
Interfaces Cérebro-Computador , Encéfalo/fisiologia , Próteses Neurais , Neurônios/fisiologia , Animais , Encéfalo/citologia , Humanos
14.
J Neurosci ; 34(47): 15576-86, 2014 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-25411486

RESUMO

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions.


Assuntos
Córtex Motor/fisiologia , Movimento/fisiologia , Animais , Estado de Descerebração/fisiopatologia , Eletromiografia , Membro Posterior/inervação , Membro Posterior/fisiologia , Masculino , Neurônios/fisiologia , Ratos , Ratos Long-Evans , Recompensa , Comportamento Estereotipado/fisiologia
15.
J Neural Eng ; 11(4): 046022, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25024291

RESUMO

OBJECTIVE: Sensory processing of peripheral information is not stationary but is, in general, a dynamic process related to the behavioral state of the animal. Yet the link between the state of the behavior and the encoding properties of neurons is unclear. This report investigates the impact of the behavioral state on the encoding mechanisms used by cortical neurons for both detection and discrimination of somatosensory stimuli in awake, freely moving, rats. APPROACH: Neuronal activity was recorded from the primary somatosensory cortex of five rats under two different behavioral states (quiet versus whisking) while electrical stimulation of increasing stimulus strength was delivered to the mystacial pad. Information theoretical measures were then used to measure the contribution of different encoding mechanisms to the information carried by neurons in response to the whisker stimulation. MAIN RESULTS: We found that the behavioral state of the animal modulated the total amount of information conveyed by neurons and that the timing of individual spikes increased the information compared to the total count of spikes alone. However, the temporal information, i.e. information exclusively related to when the spikes occur, was not modulated by behavioral state. SIGNIFICANCE: We conclude that information about somatosensory stimuli is modulated by the behavior of the animal and this modulation is mainly expressed in the spike count while the temporal information is more robust to changes in behavioral state.


Assuntos
Potenciais de Ação/fisiologia , Córtex Cerebral/fisiologia , Vigília/fisiologia , Animais , Comportamento Animal/fisiologia , Estimulação Elétrica , Eletrodos Implantados , Ratos , Córtex Somatossensorial/fisiologia , Vibrissas/inervação , Vibrissas/fisiologia
16.
Exp Neurol ; 248: 72-84, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23707218

RESUMO

The role of inhibitory neuronal activity in the transition to seizure is unclear. On the one hand, seizures are associated with excessive neuronal activity that can spread across the brain, suggesting run-away excitation. On the other hand, recent in vitro studies suggest substantial activity of inhibitory interneurons prior to the onset of evoked seizure-like activity. Yet, little is known about the behavior of interneurons before and during spontaneous seizures in chronic temporal lobe epilepsy. Here, we examined the relationship between the on-going local field potential (LFP) and the activity of populations of hippocampal neurons during the transition to spontaneous seizures in the pilocarpine rat model of epilepsy. Pilocarpine treated rats that exhibited spontaneous seizures were implanted with drivable tetrodes including an LFP electrode and recordings were obtained from the CA3 region. For each recorded seizure, identified single units were classified into putative interneurons or pyramidal cells based on average firing rate, autocorrelation activity and waveform morphology. The onset of sustained ictal spiking, a consistent seizure event that occurred within seconds after the clinically defined seizure onset time, was used to align data from each seizure to a common reference point. Ictal spiking, in this paper, refers to spiking activity in the low-pass filtered LFP during seizures and not the neuronal action potentials. Results show that beginning minutes before the onset of sustained ictal spiking in the local field, subpopulations of putative interneurons displayed a sequence of synchronous behaviors. This includes progressive synchrony with local field oscillations at theta, gamma, and finally ictal spiking frequencies, and an increased firing rate seconds before the onset of ictal spiking. Conversely, putative pyramidal cells did not exhibit increased synchrony or firing rate until after ictal spiking had begun. Our data suggest that the transition to spontaneous seizure in this network is not mediated by increasing excitatory activity, but by distinct changes in the dynamical state of putative interneurons. While these states are not unique for seizure onset, they suggest a series of state transitions that continuously increase the likelihood of a seizure. These data help to interpret the link between in vitro studies demonstrating interneuron activation at the transition to seizure, and human studies demonstrating heterogeneous neuronal firing at this time.


Assuntos
Potenciais de Ação/fisiologia , Região CA3 Hipocampal/fisiopatologia , Neurônios/fisiologia , Convulsões/fisiopatologia , Animais , Eletroencefalografia , Masculino , Pilocarpina , Células Piramidais/fisiologia , Ratos , Ratos Long-Evans , Convulsões/induzido quimicamente
17.
PLoS One ; 8(1): e54350, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23349859

RESUMO

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain.


Assuntos
Córtex Cerebral/fisiopatologia , Exercício , Condicionamento Físico Animal/fisiologia , Traumatismos da Medula Espinal/terapia , Adenilil Ciclases/metabolismo , Adenilil Ciclases/fisiologia , Animais , Animais Recém-Nascidos , Mapeamento Encefálico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Membro Posterior/metabolismo , Membro Posterior/fisiologia , Humanos , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/fisiopatologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
18.
Exp Neurol ; 241: 84-94, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23262119

RESUMO

Cortical reorganization plays a significant role in recovery of function after injury of the central nervous system. The neural mechanisms that underlie this reorganization may be the same as those normally responsible for skilled behaviors that accompany extended sensory experience and, if better understood, could provide a basis for further promoting recovery of function after injury. The work presented here extends studies of spontaneous cortical reorganization after spinal cord injury to the role of rehabilitative strategies on cortical reorganization. We use a complete spinal transection model to focus on cortical reorganization in response to serotonergic (5-HT) pharmacotherapy without any confounding effects from spared fibers left after partial lesions. 5-HT pharmacotherapy has previously been shown to improve behavioral outcome after SCI but the effect on cortical organization is unknown. After a complete spinal transection in the adult rat, 5-HT pharmacotherapy produced more reorganization in the sensorimotor cortex than would be expected by transection alone. This reorganization was dose dependent, extended into intact (forelimb) motor cortex, and, at least in the hindlimb sensorimotor cortex, followed a somatotopic arrangement. Animals with the greatest behavioral outcome showed the greatest extent of cortical reorganization suggesting that the reorganization is likely to be in response to both direct effects of 5-HT on cortical circuits and indirect effects in response to the behavioral improvement below the level of the lesion.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/uso terapêutico , Córtex Cerebral/efeitos dos fármacos , Quipazina/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Análise de Variância , Animais , Mapeamento Encefálico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Comportamento Exploratório/efeitos dos fármacos , Feminino , Membro Posterior/fisiopatologia , Transtornos Psicomotores/tratamento farmacológico , Transtornos Psicomotores/etiologia , Quipazina/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Pele/inervação , Pele/fisiopatologia , Traumatismos da Medula Espinal/complicações , Fatores de Tempo
19.
Exp Neurol ; 240: 17-27, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23159333

RESUMO

Cortical reorganization or expansion of the intact cortical regions into the deafferented cortex after complete spinal transection in neonatally spinalized rats was shown to be essential for increases in weight-supported stepping at adulthood. The novel somatotopic organization identified in these animals can be induced by exercise or spinal transplants that bridge the site of injury. However, the role of cortical reorganization in increased weight-supported (WS) stepping after pharmacotherapy is unknown. For the neonatally spinalized rat model, the 5-HT(2C) receptor agonist 1-(m-chlorophenyl)-piperazine hydrochloride (mCPP) increases the number of WS steps taken when administered to adult rats spinalized as neonates (mCPP+) though not all animals showed this effect (mCPP-). Since no differences in the behavior of the animals off-drug has been demonstrated, it is unclear why acute administration of 5-HT affects only a subset of animals. One possibility is that differences in cortical organization between mCPP+ and mCPP- may contribute to the differences in the functional effect of mCPP. To test this, we recorded from single neurons in the deafferented hindlimb sensorimotor cortex during passive sensory stimulation of the cutaneous surface of the forepaws and during active sensorimotor stimulation of the forepaws while the animals locomoted on a motorized treadmill. Our results show that neurons recorded from mCPP+ animals increased their responsiveness to both passive and active stimulation off-drug in comparison to neurons from mCPP- animals. These data suggest that differences in the cortical organization of mCPP+ compared to mCPP- animals may be at least partially responsible for the effect of a 5-HT(2C) receptor agonist on functional outcome.


Assuntos
Córtex Motor/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Piperazinas/farmacologia , Serotonina/farmacologia , Córtex Somatossensorial/fisiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Animais Recém-Nascidos , Mapeamento Encefálico/métodos , Modelos Animais de Doenças , Feminino , Córtex Motor/citologia , Córtex Motor/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/farmacologia , Córtex Somatossensorial/citologia , Córtex Somatossensorial/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia
20.
Front Syst Neurosci ; 6: 67, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23055956

RESUMO

The gradual buildup of neural activity over experimentally imposed delay periods, termed climbing activity, is well documented and is a potential mechanism by which interval time is encoded by distributed cortico-thalamico-striatal networks in the brain. Additionally, when multiple delay periods are incorporated, this activity has been shown to scale its rate of climbing proportional to the delay period. However, it remains unclear whether these patterns of activity occur within areas of motor cortex dedicated to hindlimb movement. Moreover, the effects of behavioral training (e.g., motor tasks) under different reward conditions but with similar behavioral output are not well addressed. To address this, we recorded activity from the hindlimb sensorimotor cortex (HLSMC) of two groups of rats performing a skilled hindlimb press task. In one group, rats were trained only to a make a valid press within a finite window after cue presentation for reward (non-interval trained, nIT; n = 5), while rats in the second group were given duration-specific cues in which they had to make presses of either short or long duration to receive reward (interval trained, IT; n = 6). Using perievent time histogram (PETH) analyses, we show that cells recorded from both groups showed climbing activity during the task in similar proportions (35% IT and 47% nIT), however, only climbing activity from IT rats was temporally scaled to press duration. Furthermore, using single trial decoding techniques (Wiener filter), we show that press duration can be inferred using climbing activity from IT animals (R = 0.61) significantly better than nIT animals (R = 0.507, p < 0.01), suggesting IT animals encode press duration through temporally scaled climbing activity. Thus, if temporal intervals are behaviorally relevant then the activity of climbing neurons is temporally scaled to encode the passage of time.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA