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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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Intracellular recordings in different conditions.(A) Whole cell voltage clamp recording in vitro from a layer 5 pyramidal neuron, mouse V1 cortex. Vclamp = −70 mV. (B) Sharp electrode current clamp recording from cat visual cortex, in vivo, supragranular layer, with a large tonic hyperpolarizing current. (C) Current clamp recording from mouse cortex, in vivo and no tonic hyperpolarizing current. Note the similarities in recordings from A and B and how they both differ from C.
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pone-0003983-g005: Intracellular recordings in different conditions.(A) Whole cell voltage clamp recording in vitro from a layer 5 pyramidal neuron, mouse V1 cortex. Vclamp = −70 mV. (B) Sharp electrode current clamp recording from cat visual cortex, in vivo, supragranular layer, with a large tonic hyperpolarizing current. (C) Current clamp recording from mouse cortex, in vivo and no tonic hyperpolarizing current. Note the similarities in recordings from A and B and how they both differ from C.

Mentions: Inspection of the data themselves may yield some insights into why phase randomization results from the mouse in vivo recordings are so different from those of in vitro voltage clamp and cat in vivo recordings (Fig. 5). In both the cat in vivo recording and voltage clamp in vitro recording, we see stereotypical waveforms superimposed on a baseline, whereas in mouse in vivo recordings we see something that approximates colored noise. In the in vitro voltage clamp recordings these waveforms are putative PSCs. As for the cat in vivo recordings, they might be the result of very large PSPs, or perhaps the result of nearly synchronous PSPs. In either case, the single events themselves are stereotypical and repeatable, and the deterministic structure of these events is lost after phase randomization (Fig. 3, phase randomization traces). Therefore, it is not surprising that these surrogates would demonstrate a loss in repeatability compared to unshuffled traces.


Statistical significance of precisely repeated intracellular synaptic patterns.

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

Intracellular recordings in different conditions.(A) Whole cell voltage clamp recording in vitro from a layer 5 pyramidal neuron, mouse V1 cortex. Vclamp = −70 mV. (B) Sharp electrode current clamp recording from cat visual cortex, in vivo, supragranular layer, with a large tonic hyperpolarizing current. (C) Current clamp recording from mouse cortex, in vivo and no tonic hyperpolarizing current. Note the similarities in recordings from A and B and how they both differ from C.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003983-g005: Intracellular recordings in different conditions.(A) Whole cell voltage clamp recording in vitro from a layer 5 pyramidal neuron, mouse V1 cortex. Vclamp = −70 mV. (B) Sharp electrode current clamp recording from cat visual cortex, in vivo, supragranular layer, with a large tonic hyperpolarizing current. (C) Current clamp recording from mouse cortex, in vivo and no tonic hyperpolarizing current. Note the similarities in recordings from A and B and how they both differ from C.
Mentions: Inspection of the data themselves may yield some insights into why phase randomization results from the mouse in vivo recordings are so different from those of in vitro voltage clamp and cat in vivo recordings (Fig. 5). In both the cat in vivo recording and voltage clamp in vitro recording, we see stereotypical waveforms superimposed on a baseline, whereas in mouse in vivo recordings we see something that approximates colored noise. In the in vitro voltage clamp recordings these waveforms are putative PSCs. As for the cat in vivo recordings, they might be the result of very large PSPs, or perhaps the result of nearly synchronous PSPs. In either case, the single events themselves are stereotypical and repeatable, and the deterministic structure of these events is lost after phase randomization (Fig. 3, phase randomization traces). Therefore, it is not surprising that these surrogates would demonstrate a loss in repeatability compared to unshuffled traces.

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