RESUMEN
Local circuits within the striatum of the basal ganglia include a small number of γ-aminobutyric acid (GABA)-ergic fast-spiking interneurons (FSI). The number of these cells is reduced in disorders of behavioral control, but it is unknown whether this is accompanied by altered electrophysiological properties. The genetically hypertensive (GH) rat strain exhibits impulsiveness and hyperactivity. We investigated if resting-state FSI activity is affected in this strain using extracellular recordings. We also examined the effect of systemic amphetamine (AMPH), a stimulant drug used in the treatment of these particular behavioral deficits. Putative FSI (pFSI) were encountered less often in GH rats compared to the Wistar control strain. pFSI in GH rats also exhibited a higher mean firing rate, higher intraburst firing rate, lower interburst interval, and shorter bursts compared to controls. AMPH increased the mean overall firing rate of Wistar rat pFSI but did not significantly alter the firing properties of this subtype in GH rats. These differences in the resting-state electrophysiological activity of pFSI in GH rats point to them as a cell type of particular interest in understanding striatal functioning across different strains.
Asunto(s)
Anfetamina/farmacología , Ganglios Basales/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Interneuronas/efectos de los fármacos , Neostriado/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Ganglios Basales/fisiología , Estimulantes del Sistema Nervioso Central/farmacología , Cuerpo Estriado/metabolismo , Interneuronas/metabolismo , Neostriado/metabolismo , Ratas , Ácido gamma-Aminobutírico/metabolismoRESUMEN
In the slow channel congenital myasthenic syndrome mutations in genes encoding the muscle acetylcholine receptor give rise to prolonged ion channel activations. The resulting cation overload in the postsynaptic region leads to damage of synaptic structures, impaired neuromuscular transmission and fatigable muscle weakness. Previously we identified and characterised in detail the properties of the slow channel syndrome mutation εL221F. Here, using this mutation, we generate a transgenic mouse model for the slow channel syndrome that expresses mutant human ε-subunits harbouring an EGFP tag within the M3-M4 cytoplasmic region, driven by a ~1500 bp region of the CHRNB promoter. Fluorescent mutant acetylcholine receptors are assembled, cluster at the motor endplates and give rise to a disease model that mirrors the human condition. Mice demonstrate mild fatigable muscle weakness, prolonged endplate and miniature endplate potentials, and variable degeneration of the postsynaptic membrane. We use our model to investigate ephedrine as a potential treatment. Mice were assessed before and after six weeks on oral ephedrine (serum ephedrine concentration 89 ± 3 ng/ml) using an inverted screen test and in vivo electromyography. Treated mice demonstrated modest benefit for screen hang time, and in measures of compound muscle action potentials and mean jitter that did not reach statistical significance. Ephedrine and salbutamol show clear benefit when used in the treatment of DOK7 or COLQ congenital myasthenic syndromes. Our results highlight only a modest potential benefit of these ß2-adrenergic receptor agonists for the treatment of the slow channel syndrome.
Asunto(s)
Adrenérgicos/uso terapéutico , Efedrina/uso terapéutico , Síndromes Miasténicos Congénitos/fisiopatología , Unión Neuromuscular/fisiopatología , Adrenérgicos/farmacología , Animales , Modelos Animales de Enfermedad , Efedrina/farmacología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Ratones , Ratones Transgénicos , Potenciales Postsinápticos Miniatura/efectos de los fármacos , Potenciales Postsinápticos Miniatura/genética , Mutación , Síndromes Miasténicos Congénitos/tratamiento farmacológico , Síndromes Miasténicos Congénitos/genética , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/genética , Receptores Colinérgicos/genética , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/genética , Resultado del TratamientoRESUMEN
The spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) inbred rat strains display behavioral differences characterized by relative increases and decreases in levels of activity. Both strains have subsequently been utilized as animal models of hyperactive and hypoactive behavioral traits. The etiology of these behavioral characteristics is poorly understood, but may stem from alterations in the physiology of selected neural circuits or catecholamine systems. This study investigated the cellular properties of neurons from three genetically related strains: the SHR; WKY; and Wistar (WI). In vivo intracellular recordings were made under urethane anesthesia from spiny projection neurons in the striatum, a brain area involved in behavioral activation. Results obtained from 71 spiny projection neurons indicate that most cellular properties of these neurons were very similar across the three strains. However, the amplitude and half-duration of both spontaneously occurring and current-evoked action potentials were found to be significantly different between the SHR and WKY strains with neurons from the SHR firing action potentials of relatively greater amplitude and shorter duration. Action potential parameters measured from the WI rats were intermediate between the two other strains. These differences in action potentials between two behaviorally distinct strains may reflect altered functioning of particular membrane conductances.
Asunto(s)
Potenciales de Acción/fisiología , Cuerpo Estriado/citología , Espinas Dendríticas/fisiología , Neuronas/ultraestructura , Ratas Endogámicas SHR/fisiología , Ratas Endogámicas WKY/fisiología , Animales , Estimulación Eléctrica/métodos , Neuronas/fisiología , Distribución Normal , Ratas , Ratas Endogámicas SHR/anatomía & histología , Ratas Endogámicas WKY/anatomía & histología , Ratas Wistar , Especificidad de la EspecieRESUMEN
The behaviour of spontaneously hypertensive rats (SHR) may model attention-deficit hyperactivity disorder. For example, SHR are hyperactive in an open field and show high terminal rates of responding on certain fixed-interval schedules. Open field behaviour has been dissociated from the accompanying spontaneous hypertension but fixed interval responding has not. We compared the fixed interval responding of two unrelated strains of genetically hypertensive rat, the SHR (n = 6) and the New Zealand genetically hypertensive rat (GH, n = 5), with their normotensive control strains, the Wistar Kyoto (WKY, n = 6) and Wistar (n = 5), respectively. Both hypertensive rat strains showed increased terminal lever-pressing rates on a multiple fixed-interval schedule (FI-EXT) compared to controls. In order to investigate the association of hypertension and the behavioural characteristics in question, an F-2 hybrid strain was obtained by cross-breeding GH and Wistar rats. When these F-2 hybrids (n = 33) were tested on the FI-EXT schedule, terminal lever-pressing rate was not correlated with blood pressure. The independent segregation of these phenotypical characteristics in the hybrids suggests independent genetic control. By contrast, other behavioural characteristics, including high lever-pressing rates during the extinction component and a tendency to emit responses in bursts, did cosegregate with terminal lever-pressing rates. Taken together, these findings suggest that the genetic loci for high blood pressure and responding on the FI-EXT schedule in these two unrelated rat strains are close but distinct.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Conducta Animal/fisiología , Hipertensión/psicología , Ratas Endogámicas/genética , Esquema de Refuerzo , Animales , Trastorno por Déficit de Atención con Hiperactividad/genética , Presión Sanguínea/genética , Condicionamiento Operante/fisiología , Modelos Animales de Enfermedad , Conducta Exploratoria/fisiología , Extinción Psicológica/fisiología , Hipertensión/fisiopatología , Ratas , Especificidad de la EspecieRESUMEN
Positive reinforcement helps to control the acquisition of learned behaviours. Here we report a cellular mechanism in the brain that may underlie the behavioural effects of positive reinforcement. We used intracranial self-stimulation (ICSS) as a model of reinforcement learning, in which each rat learns to press a lever that applies reinforcing electrical stimulation to its own substantia nigra. The outputs from neurons of the substantia nigra terminate on neurons in the striatum in close proximity to inputs from the cerebral cortex on the same striatal neurons. We measured the effect of substantia nigra stimulation on these inputs from the cortex to striatal neurons and also on how quickly the rats learned to press the lever. We found that stimulation of the substantia nigra (with the optimal parameters for lever-pressing behaviour) induced potentiation of synapses between the cortex and the striatum, which required activation of dopamine receptors. The degree of potentiation within ten minutes of the ICSS trains was correlated with the time taken by the rats to learn ICSS behaviour. We propose that stimulation of the substantia nigra when the lever is pressed induces a similar potentiation of cortical inputs to the striatum, positively reinforcing the learning of the behaviour by the rats.
Asunto(s)
Encéfalo/fisiología , Aprendizaje/fisiología , Neuronas/fisiología , Recompensa , Sustancia Negra/fisiología , Animales , Encéfalo/citología , Corteza Cerebral/fisiología , Cuerpo Estriado/fisiología , Dopamina/fisiología , Masculino , Modelos Neurológicos , Vías Nerviosas/fisiología , Ratas , Ratas Wistar , Refuerzo en Psicología , Autoestimulación , Sustancia Negra/citología , Sinapsis/fisiologíaRESUMEN
Dopamine and glutamate are key neurotransmitters involved in learning and memory mechanisms of the brain. These two neurotransmitter systems converge on nerve cells in the neostriatum. Dopamine modulation of activity-dependent plasticity at glutamatergic corticostriatal synapses has been proposed as a cellular mechanism for learning in the neostriatum. The present research investigated the role of specific subtypes of dopamine receptors in long-term potentiation (LTP) in the corticostriatal pathway, using intracellular recording from striatal neurons in a corticostriatal slice preparation. In agreement with previous reports, LTP could be induced reliably under Mg(2+)-free conditions. This Mg(2+)-free LTP was blocked by dopamine depletion and by the dopamine D-1/D-5 receptor antagonist SCH 23390 but was not blocked by the dopamine D-2 receptor antagonist remoxipride or the GABA(A) antagonist picrotoxin. In dopamine-depleted slices, the ability to induce LTP could be restored by bath application of the dopamine D-1/D-5 receptor agonist, SKF 38393. These results show that activation of dopamine D-1/D-5 receptors by either endogenous dopamine or exogenous dopamine agonists is a requirement for the induction of LTP in the corticostriatal pathway. These findings have significance for current understanding of learning and memory mechanisms of the neostriatum and for theoretical understanding of the mechanism of action of drugs used in the treatment of psychotic illnesses and Parkinson's disease.
Asunto(s)
Potenciación a Largo Plazo/fisiología , Neostriado/metabolismo , Receptores de Dopamina D1/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Corteza Cerebral/metabolismo , Dopamina/metabolismo , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Antagonistas de los Receptores de Dopamina D2 , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Antagonistas de Receptores de GABA-A , Ácido Glutámico/metabolismo , Técnicas In Vitro , Potenciación a Largo Plazo/efectos de los fármacos , Magnesio/metabolismo , Masculino , Microelectrodos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Ratas , Ratas Wistar , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inhibidores , Receptores de Dopamina D5RESUMEN
After the unilateral destruction of the dopamine input to the neostriatum there are enduring changes in rat behaviour. These have been ascribed to the loss of dopamine and the animals are often referred to as 'hemiparkinsonian'. In the denervated neostriatum, we have shown that not only are the tyrosine hydroxylase positive boutons missing, but also the medium sized densely spiny output cells have fewer spines. Spines usually have asymmetric synapses on their heads. In a recent stereological study we were able to show that there is a loss of approximately 20% of asymmetric synapses in the lesioned neostriatum by 1 mo after the lesion. Current experiments are trying to establish the specificity of this loss. So far we have evidence suggesting that there is no obvious preferential loss of synapses from either D1 or D2 receptor immunostained dendrites in the neostriatum with damaged dopamine innervation. These experiments suggest that dopamine is somehow necessary for the maintenance of corticostriatal synapses in the neostriatum. In a different series of experiments slices of cortex and neostriatum were maintained in vitro in such a way as to preserve at least some of the corticostriatal connections. In this preparation we have been able to show that cortical stimulation results in robust excitatory postsynaptic potentials (EPSPs) recorded from inside striatal neurons. Using stimulation protocols derived from the experiments on hippocampal synaptic plasticity we have shown that the usual consequence of trains of high frequency stimulation of the cortex is the depression of the size of EPSPs in the striatal cell. In agreement with similar experiments by others, the effect seems to be influenced by NMDA receptors since the unblocking of these receptors with low Mg++ concentrations in the perfusate uncovers a potentiation of the EPSPs after trains of stimulation. Dopamine applied in the perfusion fluid round the slices has no effect but pulsatile application of dopamine, close to the striatal cell being recorded from, and in temporal association with the cortical trains, leads to a similar LTP like effect. The reduction of K+ channel conductance in the bath with TEA also has the effect of making cortical trains induce potentiation of corticostriatal transmission. TEA applied only to the cell being recorded from has no similar effect; the cortical stimulation again depresses the EPSP amplitude, so the site of action of TEA may well be presynaptic to the striatal cell. The morphological and physiological experiments may not necessarily be related but it is tempting to suggest that dopamine protects some corticostriatal synapses by potentiating them but that in the absence of dopamine others simply disconnect and are no longer detectable on electron microscopy.
Asunto(s)
Dopamina/fisiología , Trastornos del Movimiento/metabolismo , Neostriado/metabolismo , Vías Nerviosas/fisiología , Transmisión Sináptica , Animales , Microscopía Electrónica , RatasRESUMEN
The spiny projection neurons of the neostriatum are a site at which dopamine inputs from the substantia nigra converge with excitatory inputs from the cerebral cortex. These two systems interact in certain learning and motor control mechanisms of the brain. We investigated these interactions using intracellular recording from spiny striatal neurons in urethane-anaesthetized rats. We found that acute dopamine depletion was associated with long-term depression of corticostriatal synaptic input. Electrical stimulation of the cortex which mimicked synchronous cortical input to striatal neurons also induced long-term depression of corticostriatal inputs. In intact control animals, but not in dopamine-depleted animals, this depression was prevented or reversed by concomitant stimulation of the substantia nigra. In agreement with previous in vitro studies, our in vivo findings show that long-term depression occurs in the corticostriatal pathway, and in addition show that it is regulated by dopaminergic inputs from the substantia nigra. This form of synaptic plasticity may therefore be important for understanding disturbances of the motor system seen in humans with Parkinson's disease.
Asunto(s)
Dopamina/metabolismo , Potenciales de la Membrana/fisiología , Neostriado/metabolismo , Plasticidad Neuronal/fisiología , Sustancia Negra/fisiología , Animales , Inhibidores Enzimáticos/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Neostriado/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , alfa-Metiltirosina/farmacologíaRESUMEN
A movement task was used to investigate the effects of precued variables on reaction time. The task involved rapid rotation of a hand-held manipulandum to target locations and required either pronation or supination of the forearm through short or long extent. The effects on reaction time of precues signalling target direction, extent, or a combination of direction and extent, were measured. The longest reaction times occurred when no information about direction or extent was provided in the precue (all parameters uncertain). Complete prior specification of target position produced the shortest reaction times. Specification of direction when extent was uncertain produced a significantly larger reduction in reaction time than specification of extent when direction was uncertain. Prior specification of extent also produced a small but significant reduction in reaction time relative to the condition in which direction and extent were specified in a mutually conditional manner. The results are discussed in relation to parameter precuing and motor programming, in which the direction is programmed by the pre-selection of neurons representing the muscles to be used in the task while programming of extent is represented by their level of activity during task performance.
Asunto(s)
Atención , Desempeño Psicomotor , Tiempo de Reacción , Estimulación Acústica , Adulto , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , OrientaciónRESUMEN
High-frequency stimulation (HFS) of the cerebral cortex or underlying white matter usually induces long-term depression (LTD) in the corticostriatal pathway. Long-term potentiation (LTP) has been described in striatal cells exposed to extracellular tetraethylammonium (TEA). The facilitating effect of TEA may be due to blockade of K+ channels in the postsynaptic neurone or alternatively to presynaptic effects on the release of neurotransmitters such as glutamate or dopamine. We compared the effects of HFS on LTP in striatal cells in four groups of neurones. HFS in control conditions induced LTD (-28.6 +/- 2.0% at 20 min, n = 10) whereas HFS in extracellular TEA (30 mM) induced LTP (+51.0 +/- 24.2% at 20 min, n = 7). LTP was not induced in cells loaded with intracellular Cs (-20.3 +/- 11.4% at 20 min, n = 10) or intracellular TEA (-11.8 +/- 8.9% at 20 min, n = 10), despite comparable effects on postsynaptic responses to HFS. Since the effects of the intracellular K+ channel blockers are limited to the cell being recorded from. these findings suggest that the facilitating effect of extracellular TEA on LTP induction involves a presynaptic action.
Asunto(s)
Corteza Cerebral/fisiología , Cuerpo Estriado/fisiología , Plasticidad Neuronal/fisiología , Canales de Potasio/fisiología , Sinapsis/fisiología , Animales , Corteza Cerebral/efectos de los fármacos , Cesio/farmacología , Cuerpo Estriado/efectos de los fármacos , Espacio Extracelular/química , Técnicas In Vitro , Líquido Intracelular/química , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Microelectrodos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Plasticidad Neuronal/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Bloqueadores de los Canales de Potasio , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sinapsis/efectos de los fármacos , Tetraetilamonio/farmacologíaRESUMEN
The effect of foreperiod length on reaction time in memorized (MM) and nonmemorized (NM), precued, delayed responses was investigated. Six subjects participated in one long and one short foreperiod schedule testing session. An aiming task, using elbow supination/pronation, in response to a visual stimulus was employed. In the MM condition, target spatial information was available for a fraction of the foreperiod duration. In the NM condition, target information was available continuously until the subject attained the target position. Subjects responded with a significantly longer latency in the long foreperiod schedule. Within each foreperiod schedule, the shortest foreperiod resulted in significantly longer reaction time. However, the absolute value of foreperiod did not have a major effect on reaction time latency. Memorization and nonmemorization conditions did not affect reaction time.
Asunto(s)
Memoria , Desempeño Psicomotor , Tiempo de Reacción , Adulto , Señales (Psicología) , Femenino , Humanos , Masculino , Análisis Multivariante , Pronación/fisiología , Supinación/fisiología , Factores de TiempoRESUMEN
Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization ( state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized state and a depolarized state, but not all fired action potentials while in the state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the state, or in the proportion of time that the membrane potential was in the state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.
Asunto(s)
Neostriado/citología , Neuronas/fisiología , Potenciales de Acción , Animales , Estimulación Eléctrica , Masculino , Ratas , Ratas Sprague-Dawley , Transmisión Sináptica/fisiologíaAsunto(s)
Corteza Cerebral/fisiología , Cuerpo Estriado/fisiología , Dopamina/farmacología , Sinapsis/fisiología , Animales , Corteza Cerebral/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Estimulación Eléctrica/métodos , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neuronas/ultraestructura , Ratas , Sinapsis/efectos de los fármacos , Sinapsis/ultraestructuraRESUMEN
Learning deficits resulting from dopamine depletion suggest that striatal dopamine release is crucial for reinforcement. Recently described firing patterns of dopamine neurons in behaving monkeys show that transient increases in dopamine release are brought about by reinforcement. We describe an enduring change in the strength of synaptic transmission following pulsatile application of dopamine intended to mimic the transient increases associated with reinforcement. Intracellular records were made from neurons in slices of the rat corticostriatal system. Neurons having the properties of the medium-sized spiny neurons responded to cortical stimulation with depolarizing potentials (peak amplitude 12.0 +/- 1.3 mV; latency 9.2 +/- 0.1 ms; mean +/- S.D., n = 19), which had the properties of monosynaptic excitatory postsynaptic potentials. After trains of stimuli to the cortex had been applied in conjunction with intracellular depolarizing current, the size of these excitatory postsynaptic potentials was reduced (-27% at 20 min). Application of dopamine (approximately 30 microM) in a solution containing KCl concomitant with depolarization and presynaptic activation increased the subsequent excitatory postsynaptic potentials (+21% at 20 min) without significant lasting change in the membrane properties of the postsynaptic cell. This suggests that dopamine has an enduring, activity-dependent action on the efficacy of corticostriatal transmission, which may be a cellular basis for the learning-related effects of the nigrostriatal system.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Dopamina/farmacología , Potenciales de la Membrana/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Animales , Técnicas In Vitro , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Neuronal population activity was investigated by computer simulation of a network model based on the neostriatum. Three network topologies were studied, based on different assumptions about the synaptic connectivity among medium spiny neurons. In all networks neurons were interconnected by inhibitory synapses. The connectivity was either symmetric, in which case all connections between cells were reciprocal and equal in strength; or asymmetric. Simulations showed that networks with symmetric connectivity receiving randomly distributed afferent excitation produced stationary spatial activity patterns. In contrast, asymmetric connectivity in homogeneous networks produced slow travelling-wave activity across the network. We suggest that the shape of the medium spiny neurons is an important determinant of synaptic connectivity and that changes in the shape of these neurons caused by Huntington's disease would result in asymmetric connectivity. Slow travelling-wave activity produced by asymmetric connectivity in the neostriatum could explain some aspects of the choreic movement and some electromyographic features seen in Huntington's patients.
Asunto(s)
Simulación por Computador , Cuerpo Estriado/fisiología , Modelos Neurológicos , Cuerpo Estriado/citología , Humanos , Enfermedad de Huntington/fisiopatología , Red Nerviosa/fisiología , Vías Nerviosas/citología , Vías Nerviosas/fisiología , Neuronas/fisiologíaRESUMEN
The qualitative dynamical behaviour of a neural model based on the mammalian neostriatum was analyzed. The neostriatum was modelled as a mutually inhibitory network of physiological neurones, which was driven by excitatory afferents from the cerebral cortex. The analysis defined the conditions under which the system would enter into one of two dynamic modes, competition or co-activation, in terms of the parameters defining receptor-operated and voltage-sensitive channels in the neuronal membrane. We have previously argued that the mode of co-activation in the neostriatum may correspond to the state of muscular rigidity which occurs as a symptom of Parkinson's disease. The present work extends a preliminary analysis of a two-neurone system to a system of arbitrary size. An explicit prediction is made of the conditions under which a transition from co-activation to competition will occur, which is testable experimentally. The wavelength of a non-uniform activity pattern produced by small departures from uniform afferent drive is determined for one- and two-dimensional arrays of neurones. Two mild assumptions about the connectivity of the network were used to simplify the analysis, namely that the network was symmetric and homogeneous. The implications of departures from these assumptions for understanding the disordered movement seen in Huntington's disease are also considered.
Asunto(s)
Mamíferos/fisiología , Modelos Neurológicos , Neostriado/fisiología , Animales , Simulación por Computador , Humanos , Matemática , Red Nerviosa/fisiología , Neuronas/fisiologíaRESUMEN
The involvement of L-type calcium channels in heterosynaptic long-term depression (LTD) of the stratum radiatum input to area CA1 was studied in rat hippocampal slices. LTD of the radiatum field excitatory postsynaptic potential (EPSP) and population spike, produced by tetanization of the alveus in the presence of picrotoxin, was blocked by the calcium antagonist nimodipine and by a monoclonal antibody to the L-type calcium channel. LTD was produced in the absence of picrotoxin when the L-type calcium channel agonist, BAY-K8644, was applied. This effect was also blocked by nimodipine. These results indicate that L-type calcium channels are involved in heterosynaptic long-term depression.