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Michele Migliore

Publications and source records attributed to Michele Migliore.

16 recordsLinked to original sources
PubMed2006

Electrophysiological properties and modeling of murine vomeronasal sensory neurons in acute slice preparations.

The vomeronasal system is involved in the detection of pheromones in many mammals. Vomeronasal sensory neurons encode the behaviorally relevant information into action potentials that are directly transmitted to the accessory olfactory bulb. We developed a model of the electrical activity of mouse basal vomeronasal sensory neurons, which mimics both the voltage-gated current properties and the firing behavior of these neurons in their near-native state, using a minimal number of parameters. Data were obtained by recordings with the whole-cell voltage-clamp or current-clamp techniques from mouse basal vomeronasal sensory neurons in acute slice preparations. The resting potential ranged from -50 to -70 mV, and current injections of less than 2-10 pA induced tonic firing in most neurons. The experimentally determined firing frequency as a function of injected current was well described by a Michaelis-Menten equation and was exactly reproduced by the model, which could be used in combination with future models that will include details of the mouse vomeronasal transduction cascade.

Action Potentials↗
PubMed2005

Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation.

The first-order sensory relay for olfactory processing, the main olfactory bulb (MOB), retains the ability to acquire new interneurons throughout life. It is therefore a particularly appropriate region for studying the role of experience in sculpting neuronal networks. We found that nostril closure decreased the number of newborn granule cells in the MOB, the complexity of their dendritic arborization, and their spine density, without affecting the preexisting population of granule cells. Accordingly, the frequency of miniature synaptic inhibitory events received by mitral cells was reduced. However, due to a compensatory increase in newborn granule cell excitability, action potential-dependent GABA release was dramatically enhanced, thus counteracting the reduction in spine density and leading to an unaltered synchronization of mitral cell firing activity. Together, this study reveals a unique form of adaptive response brought about exclusively by the cohort of newborn cells and used to maintain normal functioning of the MOB.

Animals↗
PubMed2005

Opinion: an integrated approach to classifying neuronal phenotypes.

Characterizing the functional phenotypes of neurons is essential for understanding how genotypes can be related to the neural basis of behaviour. Traditional classifications of neurons by single features (such as morphology or firing behaviour) are increasingly inadequate for reflecting functional phenotypes, as they do not integrate functions across different neuronal types. Here, we describe a set of rules for identifying and predicting functional phenotypes that combine morphology, intrinsic ion channel species and their distributions in dendrites, and functional properties. This more comprehensive neuronal classification should be an improvement on traditional classifications for relating genotype to functional phenotype.

Animals↗
PubMed2005

Signal propagation in oblique dendrites of CA1 pyramidal cells.

The electrophysiological properties of the oblique branches of CA1 pyramidal neurons are largely unknown and very difficult to investigate experimentally. These relatively thin dendrites make up the majority of the apical tree surface area and constitute the main target of Schaffer collateral axons from CA3. Their electrogenic properties might have an important role in defining the computational functions of CA1 neurons. It is thus important to determine if and to what extent the back- and forward propagation of action potentials (AP) in these dendrites could be modulated by local properties such as morphology or active conductances. In the first detailed study of signal propagation in the full extent of CA1 oblique dendrites, we used 27 reconstructed three-dimensional morphologies and different distributions of the A-type K(+) conductance (K(A)), to investigate their electrophysiological properties by computational modeling. We found that the local K(A) distribution had a major role in modulating action potential back propagation, whereas the forward propagation of dendritic spikes originating in the obliques was mainly affected by local morphological properties. In both cases, signal processing in any given oblique was effectively independent of the rest of the neuron and, by and large, of the distance from the soma. Moreover, the density of K(A) in oblique dendrites affected spike conduction in the main shaft. Thus the anatomical variability of CA1 pyramidal cells and their local distribution of voltage-gated channels may suit a powerful functional compartmentalization of the apical tree.

Action Potentials↗
PubMed2004

On the initiation and propagation of dendritic spikes in CA1 pyramidal neurons.

Under certain conditions, regenerative voltage spikes can be initiated locally in the dendrites of CA1 pyramidal neurons. These are interesting events that could potentially provide neurons with additional computational abilities. Using whole-cell dendritic recordings from the distal apical trunk and proximal tuft regions and realistic computer modeling, we have determined that highly synchronized and moderately clustered inputs are required for dendritic spike initiation: approximately 50 synaptic inputs spread over 100 mum of the apical trunk/tuft need to be activated within 3 msec. Dendritic spikes are characterized by a more depolarized voltage threshold than at the soma [-48 +/- 1 mV (n = 30) vs -56 +/- 1 mV (n = 7), respectively] and are mainly generated and shaped by dendritic Na+ and K+ currents. The relative contribution of AMPA and NMDA currents is also important in determining the actual spatiotemporal requirements for dendritic spike initiation. Once initiated, dendritic spikes can easily reach the soma, but their propagation is only moderately strong, so that it can be modulated by physiologically relevant factors such as changes in the V(m) and the ionic composition of the extracellular solution. With effective spike propagation, an extremely short-latency neuronal output is produced for greatly reduced input levels. Therefore, dendritic spikes function as efficient detectors of specific input patterns, ensuring that the neuronal response to high levels of input synchrony is a precisely timed action potential output.

Action Potentials↗
PubMed2004

Semi-automated population of an online database of neuronal models (ModelDB) with citation information, using PubMed for validation.

Citations play an important role in medical and scientific databases by indicating the authoritative source of the data. Manual citation entry is tedious and prone to errors. We describe a method and make available computer scripts which automate the process of citation entry. We use an open citation project PERL module (PARSER) for parsing citation data that is then used to retrieve PubMed records to supply the (validated) reference. Our PERL scripts are available via a link in the web references section of this article.

Databases, Bibliographic↗
PubMed2003

Normalization of Ca2+ signals by small oblique dendrites of CA1 pyramidal neurons.

Oblique dendrites of CA1 pyramidal neurons predominate in stratum radiatum and receive approximately 80% of the synaptic input from Schaffer collaterals. Despite this fact, most of our understanding of dendritic signal processing in these neurons comes from studies of the main apical dendrite. Using a combination of Ca2+ imaging and whole-cell recording techniques in rat hippocampal slices, we found that the properties of the oblique dendrites differ markedly from those of the main dendrites. These different properties tend to equalize the Ca2+ rise from single action potentials as they backpropagate into the oblique dendrites from the main trunk. Evidence suggests that this normalization of Ca2+ signals results from a higher density of a transient, A-type K+ current [I(K(A))] in the oblique versus the main dendrites. The higher density of I(K(A)) may have important implications for our understanding of synaptic integration and plasticity in these structures.

4-Aminopyridine↗
PubMed2003

Text mining neuroscience journal articles to populate neuroscience databases.

We have developed a program NeuroText to populate the neuroscience databases in SenseLab (http://senselab.med.yale.edu/senselab) by mining the natural language text of neuroscience articles. NeuroText uses a two-step approach to identify relevant articles. The first step (pre-processing), aimed at 100% sensitivity, identifies abstracts containing database keywords. In the second step, potentially relevant abstracts identified in the first step are processed for specificity dictated by database architecture, and neuroscience, lexical and semantic contexts. NeuroText results were presented to the experts for validation using a dynamically generated interface that also allows expert-validated articles to be automatically deposited into the databases. Of the test set of 912 articles, 735 were rejected at the pre-processing step. For the remaining articles, the accuracy of predicting database-relevant articles was 85%. Twenty-two articles were erroneously identified. NeuroText deferred decisions on 29 articles to the expert. A comparison of NeuroText results versus the experts' analyses revealed that the program failed to correctly identify articles' relevance due to concepts that did not yet exist in the knowledgebase or due to vaguely presented information in the abstracts. NeuroText uses two "evolution" techniques (supervised and unsupervised) that play an important role in the continual improvement of the retrieval results. Software that uses the NeuroText approach can facilitate the creation of curated, special-interest, bibliography databases.

Abstracting and Indexing↗
PubMed2003

Creating knowledgebases to text-mine PUBMED articles using clustering techniques.

Knowledgebase-mediated text-mining approaches work best when processing the natural language of domain-specific text. To enhance the utility of our successfully tested program-NeuroText, and to extend its methodologies to other domains, we have designed clustering algorithms, which is the principal step in automatically creating a knowledgebase. Our algorithms are designed to improve the quality of clustering by parsing the test corpus to include semantic and syntactic parsing

Algorithms↗
PubMed2002

Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons.

We investigated the role of A-type K(+) channels for the induction of long-term potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl-d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back-propagating action potentials were boosted in the dendrites only when they were coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD 098059 or U0126 shifted the activation of dendritic K(+) channels to more hyperpolarized potentials, reduced the boosting of dendritic action potentials by EPSPs, and suppressed the induction of LTP. These results support the hypothesis that dendritic K(+) channels and the boosting of back-propagating action potentials contribute to the induction of LTP in CA1 neurons.

Action Potentials↗
PubMed2002

Pharmacological upregulation of h-channels reduces the excitability of pyramidal neuron dendrites.

The dendrites of pyramidal neurons have markedly different electrical properties from those of the soma, owing to the non-uniform distribution of voltage-gated ion channels in dendrites. It is thus possible that drugs acting on ion channels might preferentially alter dendritic, but not somatic, excitability. Using dendritic and somatic whole-cell and cell-attached recordings in rat hippocampal slices, we found that the anticonvulsant lamotrigine selectively reduced action potential firing from dendritic depolarization, while minimally affecting firing at the soma. This regional and input-specific effect resulted from an increase in the hyperpolarization-activated cation current (I(h)), a voltage-gated current present predominantly in dendrites. These results demonstrate that neuronal excitability can be altered by drugs acting selectively on dendrites, and suggest an important role for I(h) in controlling dendritic excitability and epileptogenesis.

Action Potentials↗
PubMed2002

Emerging rules for the distributions of active dendritic conductances.

A key goal in neuroscience is to explain how the operations of a neuron emerge from sets of active channels with specific dendritic distributions. If general principles can be identified for these distributions, dendritic channels should reflect the computational role of a given cell type within its functional neural circuit. Here, we discuss insights from experimental and computational data on the distribution of voltage-gated channels in dendrites, and attempt to derive rules for how their interactions implement different dendritic functions. We propose that this type of analysis will be important for understanding behavioural processes in terms of single-neuron properties, and that it constitutes a step towards a 'functional proteomics' of nerve cells, which will be essential for defining neuronal phenotypes.

Animals↗
PubMedDate not supplied

A new bursting model of CA3 pyramidal cell physiology suggests multiple locations for spike initiation.

We introduce a novel computational model of hippocampal pyramidal cells physiology based on an up-to-date, detailed description of passive and active biophysical properties and real dendritic morphology. This model constitutes a modification of a previous (1995) model which included complex calcium dynamics and Na(+), K(+), and Ca(2+) currents. Changes reflect recently acquired experimental knowledge regarding the types and spatial distributions of these currents. The updated model responds to simulated somatic current clamp stimulation with a train of spikes (burst). The shape of the burst reproduces the characteristic behavior observed experimentally, similarly to the previous model. However, an analysis of dendritic membrane voltage distribution during the burst shows that the mechanisms underlying this somatic behavior are dramatically different in the two models. In the previous model, all spikes were generated in the soma and backpropagated in the dendrites. In the updated model, in contrast, only the first spike is initiated somatically. The second somatic spike is preceded by a dendritic spike (triggered by the first spike backpropagation), which propagates both backward and forward, reaching the soma just before the rise of the second somatic spike. The third and fourth spikes are similarly caused by a complex spatio-temporal interplay between somatic and dendritic depolarization. These results suggest that the distribution of ionic currents recently characterized in hippocampal pyramidal cells can support both somatic and dendritic spike initiation. In addition, these simulations demonstrate that models with considerably different distributions of active conductances can reproduce the same experimental bursting behavior with distinct biophysical mechanisms.

Action Potentials↗
PubMedDate not supplied

On the integration of subthreshold inputs from Perforant Path and Schaffer Collaterals in hippocampal CA1 pyramidal neurons.

Using a realistic model of a CA1 hippocampal pyramidal neuron, we make experimentally testable predictions on the roles of the non-specific cation current, I(h), and the A-type Potassium current, I(A), in modulating the temporal window for the integration of the two main excitatory afferent pathways of a CA1 neuron, the Schaffer Collaterals and the Perforant Path. The model shows that the experimentally observed increase in the dendritic density of I(h) and I(A) could have a major role in constraining the temporal integration window for these inputs, in such a way that a somatic action potential (AP) is elicited only when they are activated with a relative latency consistent with the anatomical arrangement of the hippocampal circuitry.

Action Potentials↗
PubMedDate not supplied

ModelDB: A Database to Support Computational Neuroscience.

Wider dissemination and testing of computational models are crucial to the field of computational neuroscience. Databases are being developed to meet this need. ModelDB is a web-accessible database for convenient entry, retrieval, and running of published models on different platforms. This article provides a guide to entering a new model into ModelDB.

Animals↗