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1.
Semin Cell Dev Biol ; 125: 68-75, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34332885

RESUMEN

The cerebral cortex integrates sensory information with emotional states and internal representations to produce coherent percepts, form associations, and execute voluntary actions. For the cortex to optimize perception, its neuronal network needs to dynamically retrieve and encode new information. Over the last few decades, research has started to provide insight into how the cortex serves these functions. Building on classical Hebbian plasticity models, the latest hypotheses hold that throughout experience and learning, streams of feedforward, feedback, and modulatory information operate in selective and coordinated manners to alter the strength of synapses and ultimately change the response properties of cortical neurons. Here, we describe cortical plasticity mechanisms that involve the concerted action of feedforward and long-range feedback input onto pyramidal neurons as well as the implication of local disinhibitory circuit motifs in this process.


Asunto(s)
Corteza Cerebral , Modelos Neurológicos , Aprendizaje/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Sinapsis/fisiología
2.
Proc Natl Acad Sci U S A ; 118(9)2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33619110

RESUMEN

The organization of sensory maps in the cerebral cortex depends on experience, which drives homeostatic and long-term synaptic plasticity of cortico-cortical circuits. In the mouse primary somatosensory cortex (S1) afferents from the higher-order, posterior medial thalamic nucleus (POm) gate synaptic plasticity in layer (L) 2/3 pyramidal neurons via disinhibition and the production of dendritic plateau potentials. Here we address whether these thalamocortically mediated responses play a role in whisker map plasticity in S1. We find that trimming all but two whiskers causes a partial fusion of the representations of the two spared whiskers, concomitantly with an increase in the occurrence of POm-driven N-methyl-D-aspartate receptor-dependent plateau potentials. Blocking the plateau potentials restores the archetypical organization of the sensory map. Our results reveal a mechanism for experience-dependent cortical map plasticity in which higher-order thalamocortically mediated plateau potentials facilitate the fusion of normally segregated cortical representations.


Asunto(s)
Potenciales de Acción/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Red Nerviosa/fisiología , Corteza Somatosensorial/fisiología , Tálamo/fisiología , Vibrisas/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Mapeo Encefálico/métodos , Maleato de Dizocilpina/farmacología , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas del GABA/farmacología , Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/anatomía & histología , Plasticidad Neuronal/efectos de los fármacos , Imagen Óptica , Técnicas de Placa-Clamp , Picrotoxina/farmacología , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Células Piramidales/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Corteza Somatosensorial/anatomía & histología , Tálamo/anatomía & histología , Vibrisas/lesiones
3.
Nat Rev Neurosci ; 19(3): 166-180, 2018 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-29449713

RESUMEN

Humans and many other animals have an enormous capacity to learn about sensory stimuli and to master new skills. However, many of the mechanisms that enable us to learn remain to be understood. One of the greatest challenges of systems neuroscience is to explain how synaptic connections change to support maximally adaptive behaviour. Here, we provide an overview of factors that determine the change in the strength of synapses, with a focus on synaptic plasticity in sensory cortices. We review the influence of neuromodulators and feedback connections in synaptic plasticity and suggest a specific framework in which these factors can interact to improve the functioning of the entire network.


Asunto(s)
Corteza Cerebral/fisiología , Aprendizaje/fisiología , Plasticidad Neuronal , Neuronas/fisiología , Animales , Atención/fisiología , Humanos , Modelos Neurológicos , Vías Nerviosas/fisiología , Recompensa
4.
Nat Methods ; 16(11): 1105-1108, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31527839

RESUMEN

Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.org ).


Asunto(s)
Microscopía Fluorescente/instrumentación , Animales , Embrión de Pollo , Microscopía Fluorescente/métodos , Programas Informáticos
5.
Nature ; 511(7510): 471-4, 2014 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-24828045

RESUMEN

During development, thalamocortical (TC) input has a critical role in the spatial delineation and patterning of cortical areas, yet the underlying cellular and molecular mechanisms that drive cortical neuron differentiation are poorly understood. In the primary (S1) and secondary (S2) somatosensory cortex, layer 4 (L4) neurons receive mutually exclusive input originating from two thalamic nuclei: the ventrobasalis (VB), which conveys tactile input, and the posterior nucleus (Po), which conveys modulatory and nociceptive input. Recently, we have shown that L4 neuron identity is not fully committed postnatally, implying a capacity for TC input to influence differentiation during cortical circuit assembly. Here we investigate whether the cell-type-specific molecular and functional identity of L4 neurons is instructed by the origin of their TC input. Genetic ablation of the VB at birth resulted in an anatomical and functional rewiring of Po projections onto L4 neurons in S1. This induced acquisition of Po input led to a respecification of postsynaptic L4 neurons, which developed functional molecular features of Po-target neurons while repressing VB-target traits. Respecified L4 neurons were able to respond both to touch and to noxious stimuli, in sharp contrast to the normal segregation of these sensory modalities in distinct cortical circuits. These findings reveal a behaviourally relevant TC-input-type-specific control over the molecular and functional differentiation of postsynaptic L4 neurons and cognate intracortical circuits, which instructs the development of modality-specific neuronal and circuit properties during corticogenesis.


Asunto(s)
Diferenciación Celular , Vías Nerviosas/fisiología , Neuronas/citología , Neuronas/fisiología , Densidad Postsináptica/fisiología , Corteza Somatosensorial/fisiología , Núcleos Talámicos/fisiología , Animales , Axones/efectos de los fármacos , Axones/fisiología , Capsaicina/farmacología , Diferenciación Celular/efectos de los fármacos , Femenino , Masculino , Ratones Endogámicos C57BL , Vías Nerviosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Noxas/farmacología , Optogenética , Densidad Postsináptica/efectos de los fármacos , Corteza Somatosensorial/citología , Corteza Somatosensorial/efectos de los fármacos , Potenciales Sinápticos/efectos de los fármacos , Núcleos Talámicos/citología , Núcleos Talámicos/efectos de los fármacos , Tacto/fisiología , Vibrisas/efectos de los fármacos , Vibrisas/fisiología
6.
Nature ; 515(7525): 116-9, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25174710

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/fisiología
8.
J Neurosci ; 36(4): 1071-85, 2016 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-26818498

RESUMEN

In cultured vertebrate neurons, axons have a uniform arrangement of microtubules with plus-ends distal to the cell body (plus-end-out), whereas dendrites contain mixed polarity orientations with both plus-end-out and minus-end-out oriented microtubules. Rather than non-uniform microtubules, uniparallel minus-end-out microtubules are the signature of dendrites in Drosophila and Caenorhabditis elegans neurons. To determine whether mixed microtubule organization is a conserved feature of vertebrate dendrites, we used live-cell imaging to systematically analyze microtubule plus-end orientations in primary cultures of rat hippocampal and cortical neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neurons in the somatosensory cortex of living mice. In vitro and in vivo, all microtubules had a plus-end-out orientation in axons, whereas microtubules in dendrites had mixed orientations. When dendritic microtubules were severed by laser-based microsurgery, we detected equal numbers of plus- and minus-end-out microtubule orientations throughout the dendritic processes. In dendrites, the minus-end-out microtubules were generally more stable and comparable with plus-end-out microtubules in axons. Interestingly, at early stages of neuronal development in nonpolarized cells, newly formed neurites already contained microtubules of opposite polarity, suggesting that the establishment of uniform plus-end-out microtubules occurs during axon formation. We propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization. SIGNIFICANCE STATEMENT: Live-cell imaging was used to systematically analyze microtubule organization in primary cultures of rat hippocampal neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neuron in somatosensory cortex of living mice. In vitro and in vivo, all microtubules have a plus-end-out orientation in axons, whereas microtubules in dendrites have mixed orientations. Interestingly, newly formed neurites of nonpolarized neurons already contain mixed microtubules, and the specific organization of uniform plus-end-out microtubules only occurs during axon formation. Based on these findings, the authors propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization.


Asunto(s)
Axones/fisiología , Polaridad Celular/fisiología , Microtúbulos/fisiología , Neuronas/citología , Animales , Células Cultivadas , Centriolos/fisiología , Corteza Cerebral/citología , Dendritas/fisiología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/citología , Humanos , Técnicas In Vitro , Ratones , Ratones Transgénicos , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Factores de Tiempo , Tubulina (Proteína)/metabolismo
9.
J Neurosci ; 34(6): 2075-86, 2014 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-24501349

RESUMEN

The appearance and disappearance of dendritic spines, accompanied by synapse formation and elimination may underlie the experience-dependent reorganization of cortical circuits. The exact temporal relationship between spine and synapse formation in vivo remains unclear, as does the extent to which synapse formation enhances the stability of newly formed spines and whether transient spines produce synapses. We used in utero electroporation of DsRedExpress- and eGFP-tagged postsynaptic density protein 95 (PSD-95) to investigate the relationship between spine and PSD stability in mouse neocortical L2/3 pyramidal cells in vivo. Similar to previous studies, spines and synapses appeared and disappeared, even in naive animals. Cytosolic spine volumes and PSD-95-eGFP levels in spines covaried over time, suggesting that the strength of many individual synapses continuously changes in the adult neocortex. The minority of newly formed spines acquired PSD-95-eGFP puncta. Spines that failed to acquire a PSD rarely survived for more than a day. Although PSD-95-eGFP accumulation was associated with increased spine lifetimes, most new spines with a PSD did not convert into persistent spines. This indicates that transient spines may serve to produce short-lived synaptic contacts. Persistent spines that were destined to disappear showed, on average, reduced PSD-95-eGFP levels well before the actual pruning event. Altogether, our data indicate that the PSD size relates to spine stability in vivo.


Asunto(s)
Espinas Dendríticas/química , Espinas Dendríticas/ultraestructura , Guanilato-Quinasas/análisis , Guanilato-Quinasas/ultraestructura , Proteínas de la Membrana/análisis , Proteínas de la Membrana/ultraestructura , Animales , Análisis por Conglomerados , Espinas Dendríticas/fisiología , Homólogo 4 de la Proteína Discs Large , Femenino , Guanilato-Quinasas/fisiología , Masculino , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Embarazo
10.
J Neurosci ; 33(22): 9474-87, 2013 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-23719814

RESUMEN

Long-term peripheral deafferentation induces representational map changes in the somatosensory cortex. It has been suggested that dendrites and axons structurally rearrange in such paradigms. However, the extent and process of this plasticity remains elusive. To more precisely quantify deafferentation-induced structural plasticity of excitatory cells we repeatedly imaged GFP-expressing L2/3 and L5 pyramidal dendrites in the mouse barrel cortex over months after the removal of a subset of the whisker follicles (FR), a procedure that completely and permanently removes whisker-sensory input. In the same mice we imaged whisker-evoked intrinsic optical signals (IOS) to assess functional cortical map changes. FR triggered the expansion of spared whisker IOS responses, whereas they remained unchanged over months in controls. The gross structure and orientation of apical dendrite tufts remained stable over a two-month period, both in controls and after deprivation. However, terminal branch tip dynamics were slightly reduced after FR, and the formation of new dendritic spines was increased in a cell-type and location-dependent manner. Together, our data suggest that peripheral nerve lesion-induced cortical map shifts do not depend on the large scale restructuring of dendritic arbors but are rather associated with local cell-type and position-dependent changes in dendritic synaptic connectivity.


Asunto(s)
Dendritas/fisiología , Desnervación , Plasticidad Neuronal/fisiología , Neuronas Aferentes/fisiología , Corteza Somatosensorial/fisiología , Algoritmos , Animales , Mapeo Encefálico , Espinas Dendríticas/fisiología , Femenino , Proteínas Fluorescentes Verdes , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , Privación Sensorial/fisiología , Vibrisas/inervación , Vibrisas/fisiología
11.
J Neurosci ; 33(32): 12997-3009, 2013 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-23926255

RESUMEN

In Huntington's disease (HD), cognitive symptoms and cellular dysfunction precede the onset of classical motor symptoms and neuronal death in the striatum and cortex by almost a decade. This suggests that the early cognitive deficits may be due to a cellular dysfunction rather than being a consequence of neuronal loss. Abnormalities in dendritic spines are described in HD patients and in HD animal models. Available evidence indicates that altered spine and synaptic plasticity could underlie the motor as well as cognitive symptoms in HD. However, the exact kinetics of spine alterations and plasticity in HD remain unknown. We used long-term two-photon imaging through a cranial window, to track individual dendritic spines in a mouse model of HD (R6/2) as the disease progressed. In vivo imaging over a period of 6 weeks revealed a steady decrease in the density and survival of dendritic spines on cortical neurons of R6/2 mice compared with control littermates. Interestingly, we also observed increased spine formation in R6/2 mice throughout the disease. However, the probability that newly formed spines stabilized and transformed into persistent spines was greatly reduced compared with controls. In cultured neurons we found that mutant huntingtin causes a loss, in particular of mature spines. Furthermore, in R6/2 mice, aggregates of mutant huntingtin associate with dendritic spines. Alterations in dendritic spine dynamics, survival, and density in R6/2 mice were evident before the onset of motor symptoms, suggesting that decreased stability of the cortical synaptic circuitry underlies the early symptoms in HD.


Asunto(s)
Espinas Dendríticas/patología , Enfermedad de Huntington/patología , Neocórtex/patología , Neuronas/ultraestructura , Actinas/genética , Actinas/metabolismo , Factores de Edad , Animales , Células Cultivadas , Espinas Dendríticas/genética , Espinas Dendríticas/ultraestructura , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Homólogo 4 de la Proteína Discs Large , Embrión de Mamíferos , Femenino , Proteínas Fluorescentes Verdes/genética , Guanilato-Quinasas/metabolismo , Hipocampo/patología , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Enfermedad de Huntington/fisiopatología , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neocórtex/ultraestructura , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuroimagen , Neuronas/patología , Desempeño Psicomotor/fisiología , Factores de Tiempo
12.
Nat Rev Neurosci ; 10(9): 647-58, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19693029

RESUMEN

Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.


Asunto(s)
Encéfalo/fisiología , Plasticidad Neuronal/fisiología , Sinapsis/fisiología , Animales , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Humanos , Red Nerviosa/citología , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiología , Neurogénesis/fisiología
13.
Front Neural Circuits ; 17: 1138358, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334059

RESUMEN

The anterior cingulate cortex (ACC) plays a crucial role in encoding, consolidating and retrieving memories related to emotionally salient experiences, such as aversive and rewarding events. Various studies have highlighted its importance for fear memory processing, but its circuit mechanisms are still poorly understood. Cortical layer 1 (L1) of the ACC might be a particularly important site of signal integration, since it is a major entry point for long-range inputs, which is tightly controlled by local inhibition. Many L1 interneurons express the ionotropic serotonin receptor 3a (5HT3aR), which has been implicated in post-traumatic stress disorder and in models of anxiety. Hence, unraveling the response dynamics of L1 interneurons and subtypes thereof during fear memory processing may provide important insights into the microcircuit organization regulating this process. Here, using 2-photon laser scanning microscopy of genetically encoded calcium indicators through microprisms in awake mice, we longitudinally monitored over days the activity of L1 interneurons in the ACC in a tone-cued fear conditioning paradigm. We observed that tones elicited responses in a substantial fraction of the imaged neurons, which were significantly modulated in a bidirectional manner after the tone was associated to an aversive stimulus. A subpopulation of these neurons, the neurogliaform cells (NGCs), displayed a net increase in tone-evoked responses following fear conditioning. Together, these results suggest that different subpopulations of L1 interneurons may exert distinct functions in the ACC circuitry regulating fear learning and memory.


Asunto(s)
Condicionamiento Clásico , Miedo , Giro del Cíngulo , Interneuronas , Animales , Ratones , Miedo/fisiología , Giro del Cíngulo/citología , Giro del Cíngulo/fisiología , Interneuronas/fisiología , Memoria/fisiología , Condicionamiento Clásico/fisiología , Masculino , Señalización del Calcio , Receptores de Serotonina/metabolismo , Neuroglía/fisiología
14.
J Physiol ; 595(5): 1435-1436, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28095619
15.
Nature ; 441(7096): 979-83, 2006 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-16791195

RESUMEN

Functional circuits in the adult neocortex adjust to novel sensory experience, but the underlying synaptic mechanisms remain unknown. Growth and retraction of dendritic spines with synapse formation and elimination could change brain circuits. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse barrel cortex, a subset of dendritic spines appear and disappear over days, whereas most spines are persistent for months. Under baseline conditions, new spines are mostly transient and rarely survive for more than a week. Transient spines tend to be small, whereas persistent spines are usually large. Because most excitatory synapses in the cortex occur on spines, and because synapse size and the number of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are proportional to spine volume, the excitation of pyramidal neurons is probably driven through synapses on persistent spines. Here we test whether the generation and loss of persistent spines are enhanced by novel sensory experience. We repeatedly imaged dendritic spines for one month after trimming alternate whiskers, a paradigm that induces adaptive functional changes in neocortical circuits. Whisker trimming stabilized new spines and destabilized previously persistent spines. New-persistent spines always formed synapses. They were preferentially added on L5B neurons with complex apical tufts rather than simple tufts. Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits.


Asunto(s)
Espinas Dendríticas/fisiología , Neocórtex/citología , Tacto/fisiología , Animales , Espinas Dendríticas/ultraestructura , Masculino , Ratones , Ratones Transgénicos , Neuronas/citología , Neuronas/fisiología , Sinapsis , Vibrisas
16.
Neuroscience ; 489: 57-68, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34634424

RESUMEN

N-methyl-d-aspartate receptor-mediated ( spikes can be causally linked to the induction of synaptic long-term potentiation (LTP) in hippocampal and cortical pyramidal cells. However, it is unclear if they regulate plasticity at a local or global scale in the dendritic tree. Here, we used dendritic patch-clamp recordings and calcium imaging to investigate the integrative properties of single dendrites of hippocampal CA3 cells. We show that local hyperpolarization of a single dendritic segment prevents NMDA spikes, their associated calcium transients, as well as LTP in a branch-specific manner. This result provides direct, causal evidence that the single dendritic branch can operate as a functional unit in regulating CA3 pyramidal cell plasticity.


Asunto(s)
Dendritas , Receptores de N-Metil-D-Aspartato , Calcio/metabolismo , Dendritas/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Plasticidad Neuronal/fisiología , Células Piramidales/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/metabolismo
17.
Commun Biol ; 5(1): 352, 2022 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-35418660

RESUMEN

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/análisis
18.
Neuron ; 110(24): 4057-4073.e8, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36202095

RESUMEN

The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.


Asunto(s)
Longevidad , Sinapsis , Ratones , Animales , Sinapsis/fisiología , Neuronas/fisiología , Encéfalo/fisiología , Homólogo 4 de la Proteína Discs Large/metabolismo
19.
J Neurosci ; 30(14): 4927-32, 2010 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-20371813

RESUMEN

The stabilization of new spines in the barrel cortex is enhanced after whisker trimming, but its relationship to experience-dependent plasticity is unclear. Here we show that in wild-type mice, whisker potentiation and spine stabilization are most pronounced for layer 5 neurons at the border between spared and deprived barrel columns. In homozygote alphaCaMKII-T286A mice, which lack experience-dependent potentiation of responses to spared whiskers, there is no increase in new spine stabilization at the border between barrel columns after whisker trimming. Our data provide a causal link between new spine synapses and plasticity of adult cortical circuits and suggest that alphaCaMKII autophosphorylation plays a role in the stabilization but not formation of new spines.


Asunto(s)
Corteza Cerebral/fisiología , Aprendizaje/fisiología , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Vibrisas/fisiología , Animales , Corteza Cerebral/ultraestructura , Espinas Dendríticas/fisiología , Espinas Dendríticas/ultraestructura , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/ultraestructura , Sinapsis/fisiología , Sinapsis/ultraestructura
20.
Neuron ; 49(6): 861-75, 2006 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-16543134

RESUMEN

We imaged axons in layer (L) 1 of the mouse barrel cortex in vivo. Axons from thalamus and L2/3/5, or L6 pyramidal cells were identified based on their distinct morphologies. Their branching patterns and sizes were stable over times of months. However, axonal branches and boutons displayed cell type-specific rearrangements. Structural plasticity in thalamocortical afferents was mostly due to elongation and retraction of branches (range, 1-150 microm over 4 days; approximately 5% of total axonal length), while the majority of boutons persisted for up to 9 months (persistence over 1 month approximately 85%). In contrast, L6 axon terminaux boutons were highly plastic (persistence over 1 month approximately 40 %), and other intracortical axon boutons showed intermediate levels of plasticity. Retrospective electron microscopy revealed that new boutons make synapses. Our data suggest that structural plasticity of axonal branches and boutons contributes to the remodeling of specific functional circuits.


Asunto(s)
Neocórtex/citología , Neuritas , Plasticidad Neuronal/fisiología , Neuronas/clasificación , Neuronas/citología , Terminales Presinápticos , Análisis de Varianza , Animales , Diagnóstico por Imagen/métodos , Proteínas Fluorescentes Verdes/genética , Imagenología Tridimensional/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica de Transmisión/métodos , Modelos Anatómicos , Modelos Biológicos , Neocórtex/ultraestructura , Neuritas/ultraestructura , Neuronas/ultraestructura , Terminales Presinápticos/ultraestructura , Antígenos Thy-1/genética , Factores de Tiempo
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