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Biomedical subjects

Karel Svoboda

Publications and source records attributed to Karel Svoboda.

8 recordsLinked to original sources
PubMed2003

Experience strengthening transmission by driving AMPA receptors into synapses.

The mechanisms underlying experience-dependent plasticity in the brain may depend on the AMPA subclass of glutamate receptors (AMPA-Rs). We examined the trafficking of AMPA-Rs into synapses in the developing rat barrel cortex. In vivo gene delivery was combined with in vitro recordings to show that experience drives recombinant GluR1, an AMPA-R subunit, into synapses formed between layer 4 and layer 2/3 neurons. Moreover, expression of the GluR1 cytoplasmic tail, a construct that inhibits synaptic delivery of endogenous AMPA-Rs during long-term potentiation, blocked experience-driven synaptic potentiation. In general, synaptic incorporation of AMPA-Rs in vivo conforms to rules identified in vitro and contributes to plasticity driven by natural stimuli in the mammalian brain.

Animals↗
PubMed2002

Activity-dependent synaptogenesis in the adult Mammalian cortex.

Recent electron microscopic studies provide evidence that the adult cortex generates new synapses in response to sensory activity and that these structural changes can occur rapidly, within 24 hr of sensory stimulation. Together with progress imaging synapses in vivo, the stage appears set for advances in understanding the dynamics and mechanisms of experience-dependent synaptogenesis.

Animals↗
PubMed2002

The life cycle of Ca(2+) ions in dendritic spines.

Spine Ca(2+) is critical for the induction of synaptic plasticity, but the factors that control Ca(2+) handling in dendritic spines under physiological conditions are largely unknown. We studied [Ca(2+)] signaling in dendritic spines of CA1 pyramidal neurons and find that spines are specialized structures with low endogenous Ca(2+) buffer capacity that allows large and extremely rapid [Ca(2+)] changes. Under physiological conditions, Ca(2+) diffusion across the spine neck is negligible, and the spine head functions as a separate compartment on long time scales, allowing localized Ca(2+) buildup during trains of synaptic stimuli. Furthermore, the kinetics of Ca(2+) sources governs the time course of [Ca(2+)] signals and may explain the selective activation of long-term synaptic potentiation (LTP) and long-term depression (LTD) by NMDA-R-mediated synaptic Ca(2+).

Action Potentials↗
PubMed2002

Facilitation at single synapses probed with optical quantal analysis.

Many synapses can change their strength rapidly in a use-dependent manner, but the mechanisms of such short-term plasticity remain unknown. To understand these mechanisms, measurements of neurotransmitter release at single synapses are required. We probed transmitter release by imaging transient increases in [Ca(2+)] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in individual dendritic spines of CA1 pyramidal neurons in rat brain slices, enabling quantal analysis at single synapses. We found that changes in release probability, produced by paired-pulse facilitation (PPF) or by manipulation of presynaptic adenosine receptors, were associated with changes in glutamate concentration in the synaptic cleft, indicating that single synapses can release a variable amount of glutamate per action potential. The relationship between release probability and response size is consistent with a binomial model of vesicle release with several (>5) independent release sites per active zone, suggesting that multivesicular release contributes to facilitation at these synapses.

2-Chloroadenosine↗
PubMed2002

Structure and function of dendritic spines.

Spines are neuronal protrusions, each of which receives input typically from one excitatory synapse. They contain neurotransmitter receptors, organelles, and signaling systems essential for synaptic function and plasticity. Numerous brain disorders are associated with abnormal dendritic spines. Spine formation, plasticity, and maintenance depend on synaptic activity and can be modulated by sensory experience. Studies of compartmentalization have shown that spines serve primarily as biochemical, rather than electrical, compartments. In particular, recent work has highlighted that spines are highly specialized compartments for rapid large-amplitude Ca(2+) signals underlying the induction of synaptic plasticity.

Animals↗
PubMed2002

An image analysis algorithm for dendritic spines.

The structure of neuronal dendrites and their spines underlie the connectivity of neural networks. Dendrites, spines, and their dynamics are shaped by genetic programs as well as sensory experience. Dendritic structures and dynamics may therefore be important predictors of the function of neural networks. Based on new imaging approaches and increases in the speed of computation, it has become possible to acquire large sets of high-resolution optical micrographs of neuron structure at length scales small enough to resolve spines. This advance in data acquisition has not been accompanied by comparable advances in data analysis techniques; the analysis of dendritic and spine morphology is still accomplished largely manually. In addition to being extremely time intensive, manual analysis also introduces systematic and hard-to-characterize biases. We present a geometric approach for automatically detecting and quantifying the three-dimensional structure of dendritic spines from stacks of image data acquired using laser scanning microscopy. We present results on the measurement of dendritic spine length, volume, density, and shape classification for both static and time-lapse images of dendrites of hippocampal pyramidal neurons. For spine length and density, the automated measurements in static images are compared with manual measurements. Comparisons are also made between automated and manual spine length measurements for a time-series data set. The algorithm performs well compared to a human analyzer, especially on time-series data. Automated analysis of dendritic spine morphology will enable objective analysis of large morphological data sets. The approaches presented here are generalizable to other aspects of neuronal morphology.

Algorithms↗
PubMedDate not supplied

Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex.

Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.

Absorptiometry, Photon↗