RESUMEN
Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity.
Asunto(s)
Complejo Nuclear Basolateral/metabolismo , Condicionamiento Clásico/fisiología , Proteínas del Citoesqueleto/metabolismo , Miedo/fisiología , Memoria/fisiología , Proteínas del Tejido Nervioso/metabolismo , Estimulación Acústica/efectos adversos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Complejo Nuclear Basolateral/citología , Estimulantes del Sistema Nervioso Central/farmacología , Colina O-Acetiltransferasa/metabolismo , Proteínas del Citoesqueleto/genética , Glutamato Descarboxilasa/metabolismo , Técnicas In Vitro , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Neuronas/fisiología , Técnicas de Placa-Clamp , Fosfopiruvato Hidratasa/metabolismo , Picrotoxina/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismoRESUMEN
Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2--10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons phase-locked in the 5- to 50-Hz range. For the amplitudes studied here, spike time reliability was always highest during 1:1 phase-locking, between 5 and 20 Hz for pyramidal cells and between 5 and 50 Hz for interneurons. The observed differences in the intrinsic frequency preference between pyramidal cells and interneurons have implications for rhythmogenesis and information transmission between populations of cortical neurons.