RESUMEN
Quantification of complexity in neurophysiological signals has been studied using different methods, especially those from information or dynamical system theory. These studies have revealed a dependence on different states of consciousness, and in particular that wakefulness is characterized by a greater complexity of brain signals, perhaps due to the necessity for the brain to handle varied sensorimotor information. Thus, these frameworks are very useful in attempts to quantify cognitive states. We set out to analyze different types of signals obtained from scalp electroencephalography (EEG), intracranial EEG and magnetoencephalography recording in subjects during different states of consciousness: resting wakefulness, different sleep stages and epileptic seizures. The signals were analyzed using a statistical (permutation entropy) and a deterministic (permutation Lempel-Ziv complexity) analytical method. The results are presented in complexity versus entropy graphs, showing that the values of entropy and complexity of the signals tend to be greatest when the subjects are in fully alert states, falling in states with loss of awareness or consciousness. These findings were robust for all three types of recordings. We propose that the investigation of the structure of cognition using the frameworks of complexity will reveal mechanistic aspects of brain dynamics associated not only with altered states of consciousness but also with normal and pathological conditions.
RESUMEN
We seek general principles of the structure of the cellular collective activity associated with conscious awareness. Can we obtain evidence for features of the optimal brain organization that allows for adequate processing of stimuli and that may guide the emergence of cognition and consciousness? Analyzing brain recordings in conscious and unconscious states, we followed initially the classic approach in physics when it comes to understanding collective behaviours of systems composed of a myriad of units: the assessment of the number of possible configurations (microstates) that the system can adopt, for which we use a global entropic measure associated with the number of connected brain regions. Having found maximal entropy in conscious states, we then inspected the microscopic nature of the configurations of connections using an adequate complexity measure and found higher complexity in states characterized not only by conscious awareness but also by subconscious cognitive processing, such as sleep stages. Our observations indicate that conscious awareness is associated with maximal global (macroscopic) entropy and with the short time scale (microscopic) complexity of the configurations of connected brain networks in pathological unconscious states (seizures and coma), but the microscopic view captures the high complexity in physiological unconscious states (sleep) where there is information processing. As such, our results support the global nature of conscious awareness, as advocated by several theories of cognition. We thus hope that our studies represent preliminary steps to reveal aspects of the structure of cognition that leads to conscious awareness.
Asunto(s)
Encéfalo/fisiología , Estado de Conciencia/fisiología , Modelos Neurológicos , Encéfalo/fisiopatología , Lesiones Encefálicas/fisiopatología , Cognición/fisiología , Coma/fisiopatología , Electroencefalografía , Entosis , Epilepsia/fisiopatología , Humanos , Magnetoencefalografía , Vías Nerviosas/fisiología , Vías Nerviosas/fisiopatología , Convulsiones/fisiopatología , Sueño/fisiologíaRESUMEN
It is said that complexity lies between order and disorder. In the case of brain activity and physiology in general, complexity issues are being considered with increased emphasis. We sought to identify features of brain organization that are optimal for sensory processing, and that may guide the emergence of cognition and consciousness, by analyzing neurophysiological recordings in conscious and unconscious states. We find a surprisingly simple result: Normal wakeful states are characterized by the greatest number of possible configurations of interactions between brain networks, representing highest entropy values. Therefore, the information content is larger in the network associated to conscious states, suggesting that consciousness could be the result of an optimization of information processing. These findings help to guide in a more formal sense inquiry into how consciousness arises from the organization of matter.
Asunto(s)
Estado de Conciencia/fisiología , Modelos Neurológicos , Red Nerviosa/fisiología , Encéfalo/fisiología , Interpretación Estadística de Datos , Entropía , HumanosRESUMEN
The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K+ and a small Na+ component. We previously reported that a Na+ -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na+ current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp recording and computational modeling approaches were carried out in isolated RPeD1 neurons. The whole-cell current of the major ion channel components in RPeD1 neurons were characterized, and a conductance-based computational model of the rhythmic pacemaker activity was simulated with the experimental measurements. We found that the spiking rate is more sensitive to changes in the Na+ leak current as compared to the K+ leak current, suggesting a robust function of Na+ leak current in regulating spontaneous neuronal firing activity. Our study provides new insight into our current understanding of the role of Na+ leak current in intrinsic properties of pacemaker neurons.
Asunto(s)
Potenciales de Acción , Modelos Neurológicos , Canales de Sodio/fisiología , Animales , Relojes Biológicos , Lymnaea , Potenciales de la Membrana , Canales de Potasio/fisiología , Canales de Potasio de Dominio Poro en Tándem , Cultivo Primario de Células , RespiraciónRESUMEN
We introduce a new 3-D flexible microelectrode array for high performance electrographic neural signal recording and stimulation. The microelectrode architecture maximizes the number of channels on each shank and minimizes its footprint. The electrode was implemented on flexible polyimide substrate using microfabrication and thin-film processing. The electrode has a planar layout and comprises multiple shanks. Each shank is three mm in length and carries six gold pads representing the neuro-interfacing channels. The channels are used in recording important precursors with potential clinical relevance and consequent electrical stimulation to perturb the clinical condition. The polyimide structure satisfied the mechanical characteristics required for the proper electrode implantation and operation. Pad postprocessing technique was developed to improve the electrode electrical performance. The planar electrodes were used for creating 3-D "Waterloo Array" microelectrode with controlled gaps using custom designed stackers. Electrode characterization and benchmarking against commercial equivalents demonstrated the superiority of the Flex electrodes. The Flex and commercial electrodes were associated with low-power implantable responsive neuro-stimulation system. The electrodes performance in recording and stimulation application was quantified through in vitro and in vivo acute and chronic experiments on human brain slices and freely-moving rodents. The Flex electrodes exhibited remarkable drop in the electric impedance (100 times at 100 Hz), improved electrode-electrolyte interface noise (dropped by four times) and higher signal-to-noise ratio (3.3 times).
Asunto(s)
Estimulación Eléctrica/instrumentación , Microelectrodos , Monitoreo Fisiológico/instrumentación , Algoritmos , Animales , Diseño de Equipo , Nanotecnología , Ratas , Ratas Wistar , Relación Señal-Ruido , Propiedades de SuperficieRESUMEN
Intracortical microelectrodes play a prominent role in the operation of neural interfacing systems. They provide an interface for recording neural activities and modulating their behavior through electric stimulation. The performance of such systems is thus directly meliorated by advances in electrode technology. We present a new architecture for intracortical electrodes designed to increase the number of recording/stimulation channels for a given set of shank dimensions. The architecture was implemented on silicon using microfabrication process and fabricated 3-mm-long electrode shanks with six relatively large (110 µm ×110 µm) pads in each shank for electrographic signal recording to detect important precursors with potential clinical relevance and electrical stimulation to correct neural behavior with low-power dissipation in an implantable device. Moreover, an electrode mechanical design was developed to increase its stiffness and reduce shank deflection to improve spatial accuracy during an electrode implantation. Furthermore, the pads were post-processed using pulsated low current electroplating and reduced their impedances by ≈ 30 times compared to the traditionally fabricated pads. The paper also presents microfabrication process, electrodes characterization, comparison to the commercial equivalents, and in vitro and in vivo validations.
Asunto(s)
Potenciales de Acción/fisiología , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Hipocampo/fisiología , Análisis por Micromatrices/instrumentación , Microelectrodos , Animales , Células Cultivadas , Diseño Asistido por Computadora , Impedancia Eléctrica , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Metales , Ratas , Ratas WistarRESUMEN
The nucleus accumbens (Acb) is a part of the striatum which integrates information from cortical and limbic brain structures, and mediates behaviors which reinforce reward. Previous work has suggested that neuronal synchrony mediated by gap junctions in Acb-related areas is involved in brain pleasure and reward. In order to gain insight into functional aspects of the neural information processing at the level of the striatum, we explored the possible role of Acb gap junctional communication and chemical synapses on reward self-stimulation in rats using positive reinforcement. Rats were trained to press a lever that caused an electrical current to be delivered into the hypothalamus, which is recognized to cause pleasure/reward. Intracerebral infusion into the Acb of the gap junctional blocker carbenoxolone (CBX) decreased the lever-pressing activity. Considering that the net effect of blocking gap junctions is a reduced synchronized output of the cellular activities, which at some level represents a decrease in excitability, two other inhibitors of neuronal excitability, carbamazepine (CBZ) and tetrodotoxin (TTX), were infused into the Acb and their effects on lever-pressing assessed. All manipulations that diminished excitability in the Acb resulted in reduced lever-pressing activity. CBX and TTX were also infused into motor cortex mediating forelimb lever-pressing with no effect. However, a manipulation that has the net effect of increasing excitation, the infusion of the opiate antagonist naloxone, also decreased significantly brain self-stimulation. We conclude that reward behaviors depend to a great extent on both excitability and gap junction-mediated mechanisms in Acb neuronal networks. Thus, the Acb provides a site for the study of pleasure/reward, addiction and conscious experience.
Asunto(s)
Uniones Comunicantes/fisiología , Núcleo Accumbens/fisiología , Recompensa , Transducción de Señal/fisiología , Animales , Carbamazepina/administración & dosificación , Carbenoxolona/administración & dosificación , Fármacos del Sistema Nervioso Central/administración & dosificación , Estimulación Eléctrica , Uniones Comunicantes/efectos de los fármacos , Hipotálamo/fisiología , Masculino , Actividad Motora/efectos de los fármacos , Corteza Motora/efectos de los fármacos , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Neuronas/efectos de los fármacos , Neuronas/fisiología , Núcleo Accumbens/efectos de los fármacos , Ratas , Ratas Wistar , Refuerzo en Psicología , Transducción de Señal/efectos de los fármacos , Bloqueadores de los Canales de Sodio/administración & dosificación , Tetrodotoxina/administración & dosificaciónRESUMEN
Current theories of brain function propose that the coordinated integration of transient activity patterns in distinct brain regions is the essence of brain information processing. The behavioural manifestations of individuals with autism spectrum disorders (ASD) suggest that their brains have a different style of information processing. Specifically, a current trend is to invoke functional disconnection in the brains of individuals with ASD as a possible explanation for some atypicalities in the behaviour of these individuals. Our observations indicate that the coordinated activity in brains of children with autism is lower than that found in control participants. Disruption of long-range phase synchronization among frontal, parietal and occipital areas was found, derived from magnetoencephalographic (MEG) recordings, in high-functioning children with ASD during the performance of executive function tasks and was associated with impaired execution, while enhanced long-range brain synchronization was observed in control children. Specifically, a more significant prefrontal synchronization was found in control participants during task performance. In addition, a robust enhancement in synchrony was observed in the parietal cortex of children with ASD relative to controls, which may be related to parietal lobe abnormalities detected in these individuals. These results, using synchronization analysis of brain electrical signals, provide support for the contention that brains of individuals with autism may not be as functionally connected as that of the controls, and may suggest some therapeutic interventions to improve information processing in specific brain areas, particularly prefrontal cortices.
Asunto(s)
Trastorno Autístico/patología , Mapeo Encefálico , Lóbulo Frontal/fisiopatología , Procesos Mentales/fisiología , Lóbulo Parietal/fisiopatología , Solución de Problemas/fisiología , Adolescente , Trastorno Autístico/fisiopatología , Niño , Femenino , Humanos , Magnetoencefalografía/métodos , Masculino , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Desempeño PsicomotorRESUMEN
We describe multifrequency phase synchronization in epileptic seizures. Using magnetoencephalographic recordings from three patients suffering generalized seizures, the evidence is presented that, in addition to the commonly studied 1:1 frequency locking, there exists complex multifrequency coordination that, in some cases, follows a classical "devil's staircase." Within the limitations of observing this phenomenon in a clinical experimental setting, these observations reveal that in pathological brain activity, complex frequency locking can be found similar to that identified in certain pathological cardiac re-entrant arrhythmias. This may suggest the existence of similar re-entrant mechanisms active in cerebral neocortex during epileptic seizures.
Asunto(s)
Biofisica/métodos , Epilepsia/patología , Magnetoencefalografía/métodos , Animales , Encéfalo/patología , Sincronización Cortical , Humanos , Modelos Neurológicos , Modelos Estadísticos , Modelos Teóricos , Neocórtex , Procesamiento de Señales Asistido por Computador , Transmisión Sináptica , Factores de TiempoRESUMEN
Coordinated cellular activity is a major characteristic of nervous system function. Coupled oscillator theory offers unique avenues to address cellular coordination phenomena. In this study, we focus on the characterization of the dynamics of epileptiform activity, based on some seizures that manifest themselves with very periodic rhythmic activity, termed absence seizures. Our approach consists in obtaining experimentally the phase response curves (PRCs) in the neocortex and thalamus, and incorporating these PRCs into a model of coupled oscillators. Phase preferences of the stationary states and their stability are determined, and these results from the model are compared with the experimental recordings, and interpreted in physiological terms.
Asunto(s)
Biofisica/métodos , Encéfalo/patología , Sistema Nervioso/patología , Animales , Modelos Neurológicos , Actividad Motora , Neocórtex/patología , Oscilometría , Ratas , Ratas Wistar , Convulsiones , Tálamo/patologíaRESUMEN
Biochemical cascades initiated by oxidative stress and excitotoxic intracellular calcium rises are thought to converge on mitochondrial dysfunction. We investigated the contribution of mitochondrial dysfunction to free radical (FR) overproduction in rat CA1 pyramidal neurons of organotypic slices subjected to a hypoxic-hypoglycemic insult. Ischemia-induced FR generation was decreased by the mitochondrial complex I blocker, rotenone, indicating that mitochondria are the principal source of ischemic FR production. Measurements of mitochondrial calcium with the mitochondrial calcium probe dihydroRhod-2, revealed that FR production during and after the anoxic episode correlates with the accumulation of mitochondrial calcium. However, the mitochondrial calcium uptake inhibitor Ru360 did not prevent FR generation during ischemia and attenuated it to some degree during reoxygenation. On the other hand, the mitochondrial permeability transition blocker cyclosporinA (CsA) completely arrested both ischemic FR generation and mitochondrial calcium overload, and prevented deterioration of neuronal intrinsic membrane properties. CsA had no effect on the accumulation of intracellular calcium during ischemia-reperfusion. Nicotinamide, a blocker of NAD+ hydrolysis, reproduced the CsA effects on FR generation, mitochondrial calcium accumulation and cytoplasmic calcium increases. These observations suggest that a major determinant of ischemic FR generation in pyramidal neurons is the uncoupling of the mitochondrial respiratory chain, which may be associated with the mitochondrial permeability transition.
Asunto(s)
Isquemia Encefálica/metabolismo , Calcio/metabolismo , Radicales Libres/metabolismo , Mitocondrias/metabolismo , Células Piramidales/metabolismo , Compuestos de Anilina/química , Animales , Calcio/análisis , Calcio/antagonistas & inhibidores , Canales de Calcio , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Unión al Calcio/metabolismo , Técnicas de Cultivo , Ciclosporina/farmacología , Complejo I de Transporte de Electrón , Colorantes Fluorescentes/química , Radicales Libres/análisis , Radicales Libres/antagonistas & inhibidores , Compuestos Heterocíclicos con 3 Anillos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Líquido Intracelular/metabolismo , Mitocondrias/efectos de los fármacos , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/metabolismo , Niacinamida/farmacología , Células Piramidales/efectos de los fármacos , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Rodaminas/química , Rotenona/farmacología , Compuestos de Rutenio/farmacología , Xantenos/químicaRESUMEN
While there have been numerous theoretical studies indicating that electrotonic coupling via gap junctions interacts with the intrinsic characteristics of the coupled neurons to modify their electrical behaviour, little experimental evidence has been provided in coupled mammalian neurons. Using an artificial electrotonic junction, two distant uncoupled neurons were coupled through the computer, and the coupling conductance was varied. Tonically firing CA1 hippocampal pyramidal neurons reduced their spike firing frequency when coupled to thalamic or pyramidal cells, showing that the electrical coupling can be considered as a low-pass filter. The strength of coupling needed to entrain spike bursts of pyramidal neurons was considerably lower than the coupling needed to synchronize two neurons with different cellular characteristics (thalamic and pyramidal cells). Coupling promoted burst firing in a non-bursting cell if it was coupled to a spontaneously bursting neuron. These results support modelling studies that indicate a role for gap-junctional coupling in the synchronization of neuronal firing and the expression of low-frequency bursting.
Asunto(s)
Encéfalo/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología , Animales , Encéfalo/citología , Conductividad Eléctrica , Electrofisiología , Masculino , Células Piramidales/fisiología , Ratas , Ratas Wistar , Tálamo/citología , Tálamo/fisiologíaRESUMEN
Reactive oxygen species have been implicated in the development of seizures under pathological conditions and linked to seizure-induced neurodegeneration. There has been little direct evidence, however, of free radical production resulting from seizures. Using amygdala-kindled rats, we have examined the generation of reactive oxygen species following seizures, and their possible contribution to seizure development and seizure-induced neuronal loss. The concentrations of two products of free radical-induced lipid peroxidation, malonaldehyde and 4-hydroxy-2(E)-nonenal, were measured using colorimetric assays. Lipid peroxidation was increased in both hemispheres of kindled rats as compared to sham-operated controls. Cell death was also significantly increased in all hippocampal areas. Antioxidants (vitamin E and glutathione) prevented the rise in lipid peroxides and hippocampal neuronal death during kindling, but did not arrest the development of seizures.Thus, epileptiform activity can result in free radical production which may be one of the factors leading to cell death.
Asunto(s)
Epilepsia/fisiopatología , Excitación Neurológica/metabolismo , Degeneración Nerviosa/fisiopatología , Estrés Oxidativo/fisiología , Animales , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Epilepsia/tratamiento farmacológico , Epilepsia/patología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología , Excitación Neurológica/patología , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/patología , Ratas , Ratas Long-EvansRESUMEN
The precise molecular events of mitochondrial dysfunction, one of the last steps that irreversibly determines cellular degeneration and death, remain unknown. We introduce a novel strategy to isolate and assess the molecular mechanisms underlying mitochondrial dysfunction. Using an in vitro ischemia model, we obtained evidence for prolonged mitochondrial depolarization in rat organotypic hippocampal brain slices during reperfusion. Then, mitochondria were isolated from brain slices and mitochondrial proteins were purified on a cyclosporin-A affinity column. Cyclosporin-A is the most potent inhibitor of mitochondrial dysfunction, in particular the mitochondrial permeability transition, and therefore we hypothesized that it may interact with proteins involved in the permeability transition after mitochondria were subjected to manipulations that promote this event. Mitochondrial porin was reproducibly eluted from the affinity column using proteins from ischemic brain mitochondria, or from mitochondria exposed to oxidative stress that were used as a positive control. Anti-porin antibodies prevented mitochondrial depolarization and electrophysiological deterioration of hippocampal neurons during hypoxia-reperfusion, as measured by simultaneous fluorescence imaging and whole-cell recordings. These observations provide biochemical and functional evidence that porin is directly involved in mitochondrial dysfunction and neuronal impairment during ischemia-reperfusion, and indicate that porin could be a novel therapeutic target to prevent cellular degeneration.
Asunto(s)
Hipocampo/fisiología , Mitocondrias/fisiología , Neuronas/fisiología , Porinas/metabolismo , Daño por Reperfusión/fisiopatología , Animales , Isquemia Encefálica/fisiopatología , Fraccionamiento Celular , Embrión de Mamíferos , Hipocampo/fisiopatología , Masculino , Potenciales de la Membrana , Mitocondrias/ultraestructura , Proteínas del Tejido Nervioso/metabolismo , Neuronas/patología , Técnicas de Cultivo de Órganos , Permeabilidad , Ratas , Ratas Wistar , Canales Aniónicos Dependientes del VoltajeRESUMEN
Organotypic brain slice cultures have been used in a variety of studies on neurodegenerative processes [K.M. Abdel-Hamid, M. Tymianski, Mechanisms and effects of intracellular calcium buffering on neuronal survival in organotypic hippocampal cultures exposed to anoxia/aglycemia or to excitotoxins, J. Neurosci. 17, 1997, pp. 3538-3553; D.W. Newell, A. Barth, V. Papermaster, A.T. Malouf, Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures, J. Neurosci. 15, 1995, pp. 7702-7711; J.L. Perez Velazquez, M.V. Frantseva, P.L. Carlen, In vitro ischemia promotes glutamate mediated free radical generation and intracellular calcium accumulation in pyramidal neurons of cultured hippocampal slices, J. Neurosci. 23, 1997, pp. 9085-9094; L. Stoppini, L.A. Buchs, D. Muller, A simple method for organotypic cultures of nervous tissue, J. Neurosci. Methods 37, 1991, pp. 173-182; R.C. Tasker, J.T. Coyle, J.J. Vornov, The regional vulnerability to hypoglycemia induced neurotoxicity in organotypic hippocampal culture: protection by early tetrodotoxin or delayed MK 801, J. Neurosci. 12, 1992, pp. 4298-4308.]. We describe two methods to induce traumatic cell damage in hippocampal organotypic cultures. Primary trauma injury was achieved by rolling a stainless steel cylinder (0.9 g) on the organotypic slices. Secondary injury was followed after dropping a weight (0.137 g) on a localised area of the organotypic slice, from a height of 2 mm. The time course and extent of cell death were determined by measuring the fluorescence of the viability indicator propidium iodide (PI) at several time points after the injury. The initial localised impact damage spread 24 and 67 h after injury, cell death being 25% and 54%, respectively, when slices were kept at 37 degrees C. To validate these methods as models to assess neuroprotective strategies, similar insults were applied to slices at relatively low temperatures (30 degrees C), which is known to be neuroprotective [F.C. Barone, G.Z. Feuerstein, R.F. White, Brain cooling during transient focal ischaemia provides complete neuroprotection, Neurosci. Biobehav. Rev. 1, 1997, pp. 31-44; V.M. Bruno, M.P. Goldberg, L.L. Dugan, R.G. Giffard, D.W. Choi, Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen glucose deprivation or excitatory aminoacids, J. Neurochem. 4, 1994, pp. 387-392; G.C. Newman, H. Qi, F.E. Hospod, K. Grundhmann, Preservation of hippocampal brain slices with in vivo or in vitro hypothermia, Brain Res. 1, 1992, pp. 159-163; J.Y. Yager, J. Asseline, Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic ischaemic brain damage in the immature rat, Stroke, 5, 1996, pp. 919-925.]. Low temperature incubation significantly reduced cell death, now being 9% at 24 h and 14% at 67 h. Our results show that these models of moderate mechanical trauma using organotypic slice cultures can be used to study neurodegeneration and neuroprotective strategies.
Asunto(s)
Lesiones Encefálicas/etiología , Hipocampo/lesiones , Neurología/métodos , Heridas no Penetrantes/etiología , Animales , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Muerte Celular , Hipocampo/patología , Hipocampo/fisiopatología , Masculino , Neuronas/patología , Neuronas/fisiología , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Temperatura , Factores de Tiempo , Heridas no Penetrantes/patología , Heridas no Penetrantes/fisiopatologíaRESUMEN
Electrotonic synaptic communication between neurons via gap junctions (gjs) is increasingly recognized as an important synchronizing mechanism in the brain. At the same time, the biology of central nervous system (CNS) gjs is being unravelled. The pathogenesis of the abnormal neuronal synchrony underlying seizures, formerly thought to be based mainly on chemical synaptic transmission, now includes a role for gap junctional communication. This concept has been strengthened by evidence from several in vitro seizure models, in which pharmacological manipulations of gap junctional communication predictably affect the generation of seizures: blockers diminishing seizures and enhancers increasing the seizures. Evidence for interneurons, coupled in part by gjs, generating synchronous neural network activity including seizures, is presented. Also neuromodelling studies, which have enhanced our ability to understand the functional role that gap junctional communication plays in the generation and maintenance of neural synchrony and seizures, are presented. Gap junctional communication appears to be a promising target for the development of future anticonvulsant therapy.
Asunto(s)
Epilepsia/fisiopatología , Uniones Comunicantes/fisiología , Sinapsis/fisiología , Animales , Humanos , Convulsiones/fisiopatologíaRESUMEN
The old concept that the direct intercellular cytoplasmic connections between neurones participate in the coordination of neuronal activity has gained new relevance, owing to recent theoretical and experimental evidence, particularly with regard to neuronal synchronization and epileptogenesis. Computer simulations demonstrating that neurones synchronize and alter their firing patterns depending on gap-junctional communication, have provided insights into the interactions between electrotonic coupling and cellular and synaptic characteristics. Experimental manipulations of gap-junctional communication support its role in the generation and maintenance of synchronized neuronal firing and seizures. Hence, in addition to chemical transmission, direct electrotonic coupling might contribute to normal and abnormal physiological brain rhythms.