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R Yuste

Publications and source records attributed to R Yuste.

At least 37 records · Page 2Linked to original sources
PubMed1999

Developmental regulation of spine motility in the mammalian central nervous system.

The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investigated spine motility in three principal neurons of the mouse CNS: cerebellar Purkinje cells, and cortical and hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy of green fluorescent protein-labeled neurons in acute and cultured slices. In all three cell types, dendritic protrusions (filopodia and spines) were highly dynamic, exhibiting a diversity of morphological rearrangements over short (<1-min) time courses. The incidence of spine motility declined during postnatal maturation, but dynamic changes were still apparent in many spines in late-postnatal neurons. Although blockade or induction of neuronal activity did not affect spine motility, disruption of actin polymerization did. We hypothesize that this basal motility of dendritic protrusions is intrinsic to the neuron and underlies the heightened plasticity found in developing CNS.

Animals↗
PubMed1999

Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis.

Dendritic spines receive most excitatory inputs in the vertebrate brain, but their function is still poorly understood. Using two-photon calcium imaging of CA1 pyramidal neurons in rat hippocampal slices, we investigated the mechanisms by which calcium enters into individual spines in the stratum radiatum. We find three different pathways for calcium influx: high-threshold voltage-sensitive calcium channels, NMDA receptors, and an APV-resistant influx consistent with calcium-permeable AMPA or kainate receptors. These pathways vary among different populations of spines and are engaged under different stimulation conditions, with peak calcium concentrations reaching >10 microM. Furthermore, as a result of the biophysical properties of the NMDA receptor, the calcium dynamics of spines are exquisitely sensitive to the temporal coincidence of the input and output of the neuron. Our results confirm that individual spines are chemical compartments that can perform coincidence detection. Finally, we demonstrate that functional studies and optical quantal analysis of single, identified synapses is feasible in mammalian CNS neurons in brain slices.

Action Potentials↗
PubMed1999

Development and plasticity of the cerebral cortex: from molecules to maps.

The role played by environmental influences in the development of the nervous system has been subject to intense study for the last three decades. Many laboratories are currently engaged in characterizing the exact contributions of activity-dependent or -independent processes to the development of the mammalian neocortex. Here we introduce a special issue devoted to the topic and briefly review recent progress in this exciting field. At the systems level, many investigators are now distinguishing between an "establishment" phase of cortical connections, where activity-dependent and independent mechanisms could operate, and a later "maintenance" phase, which appears to be controlled by neuronal activity. A particularly interesting recent example of the role of top-down vs. bottom-up influences in the development of cortical connections is the emergence of orientation selectivity in visual cortex: we propose a synthetic view highlighting the role of the thalamo-cortical reciprocal projection in this process. Finally, at the cellular level, NMDA receptors, neurotrophins and many other molecules contribute to activity-dependent rearrangement of cortical connections during appropriate critical periods of development.

Animals↗
PubMed1999

Detecting action potentials in neuronal populations with calcium imaging.

The study of neural circuits requires methods for simultaneously recording the activity of populations of neurons. Here, using calcium imaging of neocortical brain slices we take advantage of the ubiquitous distribution of calcium channels in neurons to develop a method to reconstruct the action potentials occurring in a population of neurons. Combining calcium imaging with whole-cell or perforated patch recordings from neurons loaded with acetoxymethyl ester or potassium salt forms of calcium indicators, we demonstrate that each action potential produces a stereotyped calcium transient in the somata of pyramidal neurons. These signals are detectable without averaging, and the signal-to-noise is sufficient to carry out a reconstruction of the spiking pattern of hundreds of neurons, up to relatively high firing frequencies. This technique could in principle be applied systematically to follow the activity of neuronal populations in vitro and in vivo.

Action Potentials↗
PubMed1999

Linear summation of excitatory inputs by CA1 pyramidal neurons.

A fundamental problem in neurobiology is understanding the arithmetic that dendrites use to integrate inputs. The impact of dendritic morphology and active conductances on input summation is still unknown. To study this, we use glutamate iontophoresis and synaptic stimulation to position pairs of excitatory inputs throughout the apical, oblique, and basal dendrites of CA1 pyramidal neurons in rat hippocampal slices. Under a variety of stimulation regimes, we find a linear summation of most input combinations that is implemented by a surprising balance of boosting and shunting mechanisms. Active conductances in dendrites paradoxically serve to make summation linear. This "active linearity" can reconcile predictions from cable theory with the observed linear summation in vivo and suggests that a simple arithmetic is used by apparently complex dendritic trees.

Action Potentials↗
PubMed1998

Input summation by cultured pyramidal neurons is linear and position-independent.

The role of dendritic morphology in integration and processing of neuronal inputs is still unknown. Models based on passive cable theory suggest that dendrites serve to isolate synapses from one another. Because of decreases in driving force or resistance, two inputs onto the same dendrite would diminish their joint effect, resulting in sublinear summation. When on different dendrites, however, inputs would not interact and therefore would sum linearly. These predictions have not been rigorously tested experimentally. In addition, recent results indicate that dendrites have voltage-sensitive conductances and are not passive cables. To investigate input integration, we characterized the effects of dendritic morphology on the summation of subthreshold excitatory inputs on cultured hippocampal neurons with pyramidal morphologies. We used microiontophoresis of glutamate to systematically position inputs throughout the dendritic tree and tested the summation of two inputs by measuring their individual and joint effects. We find that summation was surprisingly linear regardless of input position. For small inputs, this linearity arose because no significant shunts or changes in driving force occurred and no voltage-dependent channels were opened. Larger inputs also added linearly, but this linearity was caused by balanced action of NMDA and IA potassium conductances. Therefore, active conductances can maintain, paradoxically, a linear input arithmetic. Furthermore, dendritic morphology does not interfere with this linearity, which may be essential for particular neuronal computations.

2-Amino-5-phosphonovalerate↗
PubMed1998

Networks of coactive neurons in developing layer 1.

Spontaneous neuronal activity plays an important role in the development of cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal-Retzius (CR) neurons in developing layer 1 are necessary for correct cortical lamination and are strategically located to coordinate early circuit activity. To characterize the spontaneous activity of CR and other layer 1 neurons during cortical development, we imaged calcium transients in populations of layer 1 neurons in hemispheres and slices from postnatal rat somato-sensory neocortex. The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups of non-CR cells showed synchronous activations and formed networks of correlated neurons superimposed in the same territory. Correlated activity among non-CR cells was mediated by a depolarizing effect of GABA and was modulated by glutamate, probably released by CR cells. Our findings demonstrate that developing layer 1 can sustain complex patterns of correlated activity and reveal a circuit mechanism that can mediate this patterned activity.

Acetylcholine↗
PubMed1997

Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices.

The computations performed within cortex are likely to be determined by its internal dynamics in addition to its pattern of afferent input. As a step toward characterizing these dynamics, we have imaged electrical activity in slices from rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In response to electrical stimulation two fluorescence signals of similar maximum amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is dependent on membrane voltage, and has a significant presynaptic component. This signal can be used to image electrical activity ratiometrically. (ii) A slow signal that peaks a few seconds after stimulation, does not reflect voltage changes, and may originate from changes in scattering properties of the slice and from interactions of the dye with the cells. The spatial pattern of fast signals obtained in response to focal stimulation of coronal slices is consistent with known interlaminar projection patterns. In tangential slices, imaging of fast signals reveals clustered horizontal responses. Finally, imaging of fast signals during epileptiform activation of the disinhibited circuit reveals propagating responses, without evidence for modular activation.

Animals↗
PubMed1996

Imaging calcium dynamics in dendritic spines.

Recent advances in optical imaging technology have enabled the measurement of Ca2+ dynamics in individual synaptic spines with high time resolution. Results from work using this new technology have confirmed the view that individual synaptic spines can act as functional chemical compartments with independent dynamics of second-messenger concentration. In particular, the ability of Ca2+ to directly mediate Hebbian coincidence detection has been confirmed.

Animals↗
PubMed1996

[Primary herpetic esophageal infection in an immunocompetent patient].

Herpetic esophageal primary infection is not a common event in immunocompetent patients. The case of a 27-year-old immunocompetent woman who developed herpetic esophagitis involving the whole esophagus as a manifestation of primary herpetic infection is presented. The endoscopic appearance initially suggested esophageal candidiasis, which is not an exceptional event.

Acyclovir↗
PubMed1995

Dendritic spines as basic functional units of neuronal integration.

Most excitatory synaptic connections occur on dendritic spines. Calcium imaging experiments have suggested that spines constitute individual calcium compartments, but recent results have challenged this idea. Using two-photon microscopy to image fluorescence with high resolution in strongly scattering tissue, we measured calcium dynamics in spines from CA1 pyramidal neurons in slices of rat hippocampus. Subthreshold synaptic stimulation and spontaneous synaptic events produced calcium accumulations that were localized to isolated spines, showed stochastic failure, and were abolished by postsynaptic blockers. Single somatic spikes induced fast-peaking calcium accumulation in spines throughout the cell. Pairing of spikes with synaptic stimulation was frequently cooperative, that is, it resulted in supralinear calcium accumulations. We conclude: (1) calcium channels exist in spine heads; (2) action potentials invade the spines; (3) spines are individual calcium compartments; and (4) spines can individually detect the temporal coincidence of pre- and postsynaptic activity, and thus serve as basic functional units of neuronal integration.

Action Potentials↗
PubMed1995

Neuronal domains in developing neocortex: mechanisms of coactivation.

The mammalian neocortex consists of columnar circuits, whose development may be controlled by patterns of spontaneous activity. Columnar domains of spontaneously coactive neurons were previously described using Ca2+ imaging of slices from developing rat neocortex. We have now investigated the cellular mechanisms responsible for the coactivation of these domains. The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol. Simultaneous intracellular and optical recordings from dye-coupled cells reveal functional coupling between developing neocortical neurons. These data support the hypothesis that a neuronal domain results from the spontaneous excitation of one or a few trigger neurons that subsequently activate, either electrically or biochemically, the rest of the cells via gap junctions.

Animals↗
PubMed1995

[Gastrointestinal hemorrhage secondary to heterotopic jejunal pancreas].

A case of heterotopic pancreas located in the small intestine is herewith presented. The 19-years male patient had been admitted three times since 1991 for an anemic syndrome secondary to melena. The origin of the hemorrhage was not determined with the studies performed (intestinal transit, opaque enema, esophagogastroscopy, colonoscopy and gammagraphy with technetium 99). On the last admission a vascular lesion low flow was observed on arteriography of the upper mesenteric artery on the mesenteric edge of the proximal jejunum. Following laparotomy a small tumor was found in the jejunum and 5 cm of the intestine including the tumor was resected. The anatomic pathologic results demonstrated a heterotopic pancreas.

Adult↗