RESUMEN
Sensory information is transmitted with high fidelity across multiple synapses until it reaches the neocortex. There, individual neurons exhibit enormous variability in responses. The source of this diversity in output has been debated. Using transgenic mice expressing the green fluorescent protein coupled to the activity-dependent gene c-fos, we identified neurons with a history of elevated activity in vivo. Focusing on layer 4 to layer 2/3 connections, a site of strong excitatory drive at an initial stage of cortical processing, we find that fluorescently tagged neurons receive significantly greater excitatory and reduced inhibitory input compared with neighboring, unlabeled cells. Differential wiring of layer 2/3 neurons arises early in development and requires sensory input to be established. Stronger connection strength is not associated with evidence for recent synaptic plasticity, suggesting that these more active ensembles may not be generated over short time scales. Paired recordings show fosGFP+ neurons spike at lower stimulus thresholds than neighboring, fosGFP- neurons. These data indicate that differences in circuit construction can underlie response heterogeneity amongst neocortical neurons.
Asunto(s)
Plasticidad Neuronal , Neuronas/fisiología , Corteza Somatosensorial/fisiología , Potenciales Sinápticos , Animales , Estimulación Eléctrica , Técnicas In Vitro , Ratones , Ratones Transgénicos , Inhibición Neural , Corteza Somatosensorial/crecimiento & desarrolloRESUMEN
VIDEO ABSTRACT: Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here, we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP(-) neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP(+) neurons. Paired-cell recordings indicated that fosGFP(+) neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information.
Asunto(s)
Potenciales de Acción/fisiología , Neocórtex/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Animales , Animales Recién Nacidos , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
Neocortical neurons show astonishing variation in the presence and timing of action potentials across stimulus trials, a phenomenon whose function and significance has been the subject of great interest. Here we present data showing that this response variability can be significantly reduced by altered sensory experience. Removal of all but one whisker from the side of the mouse face results in the rapid (within 24 h) potentiation of mean firing rates within the cortical representation of the spared whisker in young postnatal animals (postnatal days 13-16). Analysis of single-unit responses from whisker-spared animals shows that this potentiation can be attributed to an enhancement of trial-to-trial reliability (i.e., reduced response failures), as well as an increase in the mean number of spikes evoked within a successful trial. Changes were confined to superficial layers 2/3 and were not observed in the input layer of the cortex, layer 4. In addition to these changes in firing rates, we also observed profound changes in the precise timing of sensory-evoked responses. Trial-to-trial temporal precision was enhanced and the absolute latency of responses was reduced after single-whisker experience. Enhanced spike-timing precision and trial-to-trial reliability could also be triggered in adolescent animals with longer periods (7 d) of single-whisker experience. These experiments provide a quantitative analysis of how sensory experience can enhance both reliability and temporal precision in neocortical neurons and provide a framework for testing specific hypotheses about the role of response variability in cortical function and the molecular mechanisms underlying this phenomenon.
Asunto(s)
Potenciales de Acción , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Privación Sensorial/fisiología , Corteza Somatosensorial/fisiología , Animales , Potenciales Evocados Somatosensoriales , Ratones , Ratones Endogámicos C57BL , Microelectrodos , Estimulación Física , Factores de Tiempo , VibrisasRESUMEN
PURPOSE: Mutations that enhance currents through the Ca(2+)- and voltage-gated K(+) channel BK (Slo, maxiK, KCNMA1) have been associated with seizure disorders in both rodent models and humans. Previously we have found that seizures themselves induce a gain-of-function in BK channels that is associated with elevated excitability in neocortical neurons. In this study, we sought to examine whether administration of BK-channel antagonists possess anticonvulsant activity in vivo. METHODS: Seizures were induced in animals by intraperitoneal (i.p.) injection of the gamma-aminobutyric acid (GABA)(A) antagonists picrotoxin or pentylenetetrazole. Twenty-four hours following induction of the initial seizure episode, animals were reinjected with chemoconvulsant in the presence of the BK-channel antagonist paxilline or saline. The presence and duration of tonic-clonic seizures were evaluated. RESULTS: Intraperitoneal injection of paxilline was sufficient to eliminate tonic-clonic seizures in picrotoxin-treated animals. Paxilline reduced seizure duration and intensity in pentylenetetrazole-injected animals. DISCUSSION: The BK-channel antagonist paxilline possesses significant anticonvulsant activity in both picrotoxin and pentylenetetrazole seizure models, an effect that may be related to the seizure-dependent gain-of-function in BK channel previously observed in neocortical neurons in vitro.
Asunto(s)
Indoles/uso terapéutico , Bloqueadores de los Canales de Potasio/uso terapéutico , Convulsiones/tratamiento farmacológico , Análisis de Varianza , Animales , Animales Recién Nacidos , Recuento de Células/métodos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electroencefalografía/métodos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones , Ratones Endogámicos C57BL , Neocórtex/efectos de los fármacos , Neocórtex/metabolismo , Pentilenotetrazol , Picrotoxina , Proteínas Proto-Oncogénicas c-fos/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Convulsiones/inducido químicamente , Convulsiones/patología , Convulsiones/fisiopatología , Factores de TiempoRESUMEN
Each cerebral hemisphere processes sensory input from both sides of the body, but the impact of this convergence on shaping and modifying receptive field properties remains controversial. Here we investigated the effect of chronic deprivation of ipsilateral sensory whiskers on receptive field plasticity in primary somatosensory cortex. In the absence of ipsilateral whiskers, cortical receptive fields were significantly larger than control after 1 week. Removal of all but a single whisker from one side of the face [single-whisker experience (SWE)] has been shown to result in the expansion of the cortical area responding to the spared whisker. We compared the effects of SWE in the presence (SWE-unilateral) and absence (SWE-bilateral) of ipsilateral whiskers. SWE-bilateral deprivation results in a significant increase in neuronal responses to spared whisker stimulation both in its cognate barrel column and in adjacent, surrounding barrel columns compared with control and SWE-unilateral deprived animals. Surround receptive fields in deprived columns were maintained in SWE-bilateral treated animals but depressed in SWE-unilateral animals. The increase in spared whisker responses was progressive with longer deprivation periods. These data show that ipsilateral whiskers can constrain receptive field size in the barrel cortex.