RESUMEN
Activity-dependent attenuations in extracellular spike amplitude have been shown to correlate with a decrease in the effectiveness with which somatic action potentials back-propagate into the dendritic arbor of hippocampal pyramidal cells. In this paper we demonstrate that activity-dependent attenuations in amplitude occur during behavior and that the amount of attenuation is reduced with an animal's experience in an environment. The observed reductions are caused by an animal's experience within a specific environmental context, are dependent on functional NMDA receptors, and are accompanied by an increase in the effective coupling of pyramidal cells and interneurons. These results provide an important step in linking together in vivo studies with in vitro data and suggest that mechanisms of plasticity engaged during behavior may be sufficient to alter the biophysical and integrative properties of hippocampal pyramidal cells.
Asunto(s)
Potenciales de Acción/fisiología , Dendritas/fisiología , Espacio Extracelular/fisiología , Hipocampo/fisiología , Células Piramidales/fisiología , Animales , Conducta Apetitiva/fisiología , Conducta Animal , Electrodos Implantados , Ambiente , Hipocampo/citología , Interneuronas/fisiología , Aprendizaje/fisiología , Masculino , Actividad Motora/fisiología , Inhibición Neural/fisiología , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Ratas , Ratas Long-Evans , Tiempo de Reacción/fisiología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresAsunto(s)
Encéfalo/fisiología , Recompensa , Animales , Electrofisiología , Vías Nerviosas/fisiologíaRESUMEN
To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of pairs of neurons tuned to similar spatial locations. Pairs have uncorrelated firing even if their fields overlap. These results demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the proper representation of space in the CA1 region of the hippocampus.
Asunto(s)
Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Percepción Espacial/fisiología , Potenciales de Acción , Animales , Conducta Animal/fisiología , Electrofisiología , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Ratones , Ratones Noqueados , Sinapsis/fisiologíaRESUMEN
Population coding, where neurons with broad and overlapping firing rate tuning curves collectively encode information about a stimulus, is a common feature of sensory systems. We use decoding methods and measured properties of NMDA-mediated LTP induction to study the impact of long-term potentiation of synapses between the neurons of such a coding array. We find that, due to a temporal asymmetry in the induction of NMDA-mediated LTP, firing patterns in a neuronal array that initially represent the current value of a sensory input will, after training, provide an experienced-based prediction of that input instead. We compute how this prediction arises from and depends on the training experience. We also show how the encoded prediction can be used to generate learned motor sequences, such as the movement of a limb. This involves a novel form of memory recall that is driven by the motor response so that it automatically generates new information at a rate approximate for the task being performed.
Asunto(s)
Potenciación a Largo Plazo/fisiología , Aprendizaje Seriado/fisiología , Agonistas de Aminoácidos Excitadores/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Modelos Neurológicos , N-Metilaspartato/farmacología , Aprendizaje Seriado/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/fisiologíaAsunto(s)
Hipocampo/metabolismo , Aprendizaje/fisiología , Plasticidad Neuronal/fisiología , Receptores de N-Metil-D-Aspartato/genética , Percepción Espacial/fisiología , Sinapsis/fisiología , Animales , Giro Dentado/fisiología , Electrofisiología , Ratones , Ratones Noqueados , Mutación/fisiología , Receptores de N-Metil-D-Aspartato/biosíntesisRESUMEN
Using experimental facts about long-term potentiation (LTP) and hippocampal place cells, we model how a spatial map of the environment can be created in the rat hippocampus. Sequential firing of place cells during exploration induces, in the model, a pattern of LTP between place cells that shifts the location coded by their ensemble activity away from the actual location of the animal. These shifts provide a navigational map that, in a simulation of the Morris maze, can guide the animal toward its goal. The model demonstrates how behaviorally generated modifications of synaptic strengths can be read out to affect subsequent behavior. Our results also suggest a way that navigational maps can be constructed from experimental recordings of hippocampal place cells.
Asunto(s)
Mapeo Encefálico/métodos , Cognición/fisiología , Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Aprendizaje por Laberinto/fisiología , Modelos Neurológicos , Potenciales de Acción/fisiología , Animales , RatasRESUMEN
1. We present a new mathematical description of the complete distribution of electrical responses to stochastic synaptic activity (quantal analysis) that is intended as a model of experiments on central neuronal synapses. Unlike previous treatments, this distribution is calculated for each instant after the release of transmitter into the cleft. 2. We follow the traditional description of probabilistic presynaptic vesicle release. On the postsynaptic side, however, we assume that channel fluctuations are important and we take them into account. The probability of finding a given channel open after a certain amount of transmitter is released is calculated from detailed receptor/channel and neurotransmitter clearance kinetics. This approach allows us to naturally include the nonlinear dependence of open probability on the amount of transmitter released, with saturation for large transmitter doses. The distribution of open channels is calculated from this probability. 3. We also allow the possibility that multiple synaptic inputs to a target neuron may be active in a typical experiment. We have not treated cable effects. We explore the implications of multiple synapses for the nonlinearities of the system. The most important of these is that vesicles in different synapses have independent responses, and therefore their effects add linearly. 4. The resulting distributions depend heavily on what region of the nonlinear dose-response curve the synapses are in. Far from saturation, peaks in the distribution are due to vesicles, and close to saturation they are due to active synapses. Peak widths are due to channel fluctuations and instrumental noise, which we introduce to make closer contact with experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Encéfalo/fisiología , Potenciación a Largo Plazo/fisiología , Modelos Neurológicos , Neurotransmisores/fisiología , Teoría Cuántica , Transmisión Sináptica/fisiología , Animales , Simulación por Computador , Humanos , Modelos Teóricos , Neuronas/fisiología , Receptores AMPA/fisiología , Sinapsis/fisiología , Vesículas Sinápticas/fisiologíaRESUMEN
Fura-2 and imaging technology were used to detect intracellular Ca2+ changes in CA1 pyramidal cells in hippocampal slices. During focal synaptic stimulation, one or more highly localized regions of Ca2+ elevation (hot spots) were detected in the dendrites. Ca2+ spread from the center of hot spots with properties consistent with diffusion. Several lines of evidence indicate that these hot spots were due to Ca2+ entry through N-methyl-D-aspartate synaptic channels. The spatial and temporal resolution of the method was sufficient to detect the response of single hot spots to single stimuli, thus providing a real-time method for monitoring local synaptic activity. Using this method, we show that synapses on the same dendrite differ in their probability of response and in their facilitation properties.