RESUMEN
Long-term synaptic potentiation (LTP) is thought to be a key process in cortical synaptic network plasticity and memory formation. Hebbian forms of LTP depend on strong postsynaptic depolarization, which in many models is generated by action potentials that propagate back from the soma into dendrites. However, local dendritic depolarization has been shown to mediate these forms of LTP as well. As pyramidal cells in supragranular layers of the somatosensory cortex spike infrequently, it is unclear which of the two mechanisms prevails for those cells in vivo. Using whole-cell recordings in the mouse somatosensory cortex in vivo, we demonstrate that rhythmic sensory whisker stimulation efficiently induces synaptic LTP in layer 2/3 (L2/3) pyramidal cells in the absence of somatic spikes. The induction of LTP depended on the occurrence of NMDAR (N-methyl-d-aspartate receptor)-mediated long-lasting depolarizations, which bear similarities to dendritic plateau potentials. In addition, we show that whisker stimuli recruit synaptic networks that originate from the posteromedial complex of the thalamus (POm). Photostimulation of channelrhodopsin-2 expressing POm neurons generated NMDAR-mediated plateau potentials, whereas the inhibition of POm activity during rhythmic whisker stimulation suppressed the generation of those potentials and prevented whisker-evoked LTP. Taken together, our data provide evidence for sensory-driven synaptic LTP in vivo, in the absence of somatic spiking. Instead, LTP is mediated by plateau potentials that are generated through the cooperative activity of lemniscal and paralemniscal synaptic circuitry.
Asunto(s)
Dendritas/fisiología , Potenciación a Largo Plazo , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Potenciales de Acción , Animales , Channelrhodopsins , Masculino , Ratones , Ratones Endogámicos C57BL , Estimulación Física , Receptores de N-Metil-D-Aspartato/metabolismo , Tálamo/citología , Tálamo/fisiología , Vibrisas/fisiologíaRESUMEN
Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the structural plasticity of inhibitory neurons remains limited. Interneurons are divided into various subclasses, each with specialized functions in cortical circuits. Further knowledge of subclass-specific structural plasticity of interneurons is crucial to gaining a complete mechanistic understanding of their contribution to cortical plasticity overall. Here, we describe a subpopulation of superficial cortical multipolar interneurons expressing vasoactive intestinal peptide (VIP) with high spine densities on their dendrites located in layer (L) 1, and with the electrophysiological characteristics of bursting cells. Using longitudinal imaging in vivo, we found that the majority of the spines are highly dynamic, displaying lifetimes considerably shorter than that of spines on pyramidal neurons. Using correlative light and electron microscopy, we confirmed that these VIP spines are sites of excitatory synaptic contacts, and are morphologically distinct from other spines in L1.
Asunto(s)
Interneuronas , Péptido Intestinal Vasoactivo , Interneuronas/fisiología , Plasticidad Neuronal/fisiología , Neuronas , Células Piramidales/fisiología , Péptido Intestinal Vasoactivo/análisisRESUMEN
Input from the sensory organs is required to pattern neurons into topographical maps during development. Dendritic complexity critically determines this patterning process; yet, how signals from the periphery act to control dendritic maturation is unclear. Here, using genetic and surgical manipulations of sensory input in mouse somatosensory thalamocortical neurons, we show that membrane excitability is a critical component of dendritic development. Using a combination of genetic approaches, we find that ablation of N-methyl-D-aspartate (NMDA) receptors during postnatal development leads to epigenetic repression of Kv1.1-type potassium channels, increased excitability, and impaired dendritic maturation. Lesions to whisker input pathways had similar effects. Overexpression of Kv1.1 was sufficient to enable dendritic maturation in the absence of sensory input. Thus, Kv1.1 acts to tune neuronal excitability and maintain it within a physiological range, allowing dendritic maturation to proceed. Together, these results reveal an input-dependent control over neuronal excitability and dendritic complexity in the development and plasticity of sensory pathways.
Asunto(s)
Dendritas/fisiología , Neuronas/fisiología , Corteza Somatosensorial/fisiología , Tálamo/fisiología , Animales , Femenino , Perfilación de la Expresión Génica , Canal de Potasio Kv.1.1/genética , Canal de Potasio Kv.1.1/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Plasticidad Neuronal/fisiología , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Corteza Somatosensorial/citología , Transmisión Sináptica/fisiología , Tálamo/citología , Vibrisas/inervación , Vibrisas/fisiologíaRESUMEN
Synaptic activity in the neonatal brain is often locally synchronized. How such clustering comes about is unclear. Winnubst et al. (2015) show that the refinement of synaptic connectivity is driven by the depression of synapses that are asynchronous with their neighbors.