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Statistical significance of precisely repeated intracellular synaptic patterns.

Ikegaya Y, Matsumoto W, Chiou HY, Yuste R, Aaron G - PLoS ONE (2008)

Bottom Line: To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data.Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007) drew from their recent in vivo recordings.In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

ABSTRACT
Can neuronal networks produce patterns of activity with millisecond accuracy? It may seem unlikely, considering the probabilistic nature of synaptic transmission. However, some theories of brain function predict that such precision is feasible and can emerge from the non-linearity of the action potential generation in circuits of connected neurons. Several studies have presented evidence for and against this hypothesis. Our earlier work supported the precision hypothesis, based on results demonstrating that precise patterns of synaptic inputs could be found in intracellular recordings from neurons in brain slices and in vivo. To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data. Because more repeats were found in the original data than in the surrogate data sets, we argued that repeats were not due to chance occurrence. Mokeichev et al. (2007) challenged these conclusions, arguing that the generation of surrogate data was insufficiently rigorous. We have now reanalyzed our previous data with the methods introduced from Mokeichev et al. (2007). Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007) drew from their recent in vivo recordings. Moreover, we also show that the conditions under which the membrane potential is recorded contributes significantly to the ability to detect repeats and may explain conflicting results. In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.

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Related in: MedlinePlus

A cartoon illustrating how repeats of action potential sequences in a cortical network can be recorded in a single neuron.The picture depicts a pyramidal neuron being recorded with an intracellular electrode that measures postsynaptic currents (PSCs) during voltage clamp recordings. A series of action potentials in three neurons forming synapses with the neuron can be recorded. The blue trace represents such a sequence that was recorded, and the red trace shows the same sequence repeating at some later time in the recording.
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pone-0003983-g001: A cartoon illustrating how repeats of action potential sequences in a cortical network can be recorded in a single neuron.The picture depicts a pyramidal neuron being recorded with an intracellular electrode that measures postsynaptic currents (PSCs) during voltage clamp recordings. A series of action potentials in three neurons forming synapses with the neuron can be recorded. The blue trace represents such a sequence that was recorded, and the red trace shows the same sequence repeating at some later time in the recording.

Mentions: One obstacle to the study of these network patterns is the limited ability to record the participating neurons. That is, many neurons should be simultaneously recorded with a high temporal precision in order to increase the probability of detecting a network phenomenon. To overcome this problem Ikegaya et al. (2004) [7] introduced a template-matching search program for single intracellular recordings. The rationale of the technique was that since a single neuron receives 100 s to 1000 s of synaptic inputs from different neurons, then it is conceivable that a single neuron could serve as a “microphone” of the neuronal network (Fig. 1). In this study, we found remarkable examples where the intracellular currents recorded in a single neuron were seen to repeat with millisecond precision. Such examples do not mean that these phenomena could not emerge by chance alone. To examine the hypothesis of stochastic generation of precise repeats, surrogate data were generated and compared to the original data. More putative repeats were found in the original data than in the surrogate data, and so the hypothesis of stochastic generation was rejected for these recordings.


Statistical significance of precisely repeated intracellular synaptic patterns.

Ikegaya Y, Matsumoto W, Chiou HY, Yuste R, Aaron G - PLoS ONE (2008)

A cartoon illustrating how repeats of action potential sequences in a cortical network can be recorded in a single neuron.The picture depicts a pyramidal neuron being recorded with an intracellular electrode that measures postsynaptic currents (PSCs) during voltage clamp recordings. A series of action potentials in three neurons forming synapses with the neuron can be recorded. The blue trace represents such a sequence that was recorded, and the red trace shows the same sequence repeating at some later time in the recording.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2599887&req=5

pone-0003983-g001: A cartoon illustrating how repeats of action potential sequences in a cortical network can be recorded in a single neuron.The picture depicts a pyramidal neuron being recorded with an intracellular electrode that measures postsynaptic currents (PSCs) during voltage clamp recordings. A series of action potentials in three neurons forming synapses with the neuron can be recorded. The blue trace represents such a sequence that was recorded, and the red trace shows the same sequence repeating at some later time in the recording.
Mentions: One obstacle to the study of these network patterns is the limited ability to record the participating neurons. That is, many neurons should be simultaneously recorded with a high temporal precision in order to increase the probability of detecting a network phenomenon. To overcome this problem Ikegaya et al. (2004) [7] introduced a template-matching search program for single intracellular recordings. The rationale of the technique was that since a single neuron receives 100 s to 1000 s of synaptic inputs from different neurons, then it is conceivable that a single neuron could serve as a “microphone” of the neuronal network (Fig. 1). In this study, we found remarkable examples where the intracellular currents recorded in a single neuron were seen to repeat with millisecond precision. Such examples do not mean that these phenomena could not emerge by chance alone. To examine the hypothesis of stochastic generation of precise repeats, surrogate data were generated and compared to the original data. More putative repeats were found in the original data than in the surrogate data, and so the hypothesis of stochastic generation was rejected for these recordings.

Bottom Line: To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data.Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007) drew from their recent in vivo recordings.In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

ABSTRACT
Can neuronal networks produce patterns of activity with millisecond accuracy? It may seem unlikely, considering the probabilistic nature of synaptic transmission. However, some theories of brain function predict that such precision is feasible and can emerge from the non-linearity of the action potential generation in circuits of connected neurons. Several studies have presented evidence for and against this hypothesis. Our earlier work supported the precision hypothesis, based on results demonstrating that precise patterns of synaptic inputs could be found in intracellular recordings from neurons in brain slices and in vivo. To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data. Because more repeats were found in the original data than in the surrogate data sets, we argued that repeats were not due to chance occurrence. Mokeichev et al. (2007) challenged these conclusions, arguing that the generation of surrogate data was insufficiently rigorous. We have now reanalyzed our previous data with the methods introduced from Mokeichev et al. (2007). Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007) drew from their recent in vivo recordings. Moreover, we also show that the conditions under which the membrane potential is recorded contributes significantly to the ability to detect repeats and may explain conflicting results. In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.

Show MeSH
Related in: MedlinePlus