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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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Effect of membrane potential hyperpolarization on PSP detection.(A) A sample of an in vivo current clamp recording is shown at an approximate resting membrane potential of −55 mV (top) versus a sample recorded from the same neuron minutes later at −95 mV (bottom). The hyperpolarized membrane potential was induced by a tonic DC injection. Underlined segments of these recordings are expanded in (B), showing the increased ability to detect smaller PSPs during hyperpolarized membrane potentials. (C) PHRI values recorded during resting membrane potential versus artificially induced hyperpolarized membrane potentials. (top) PHRI values are calculated from 90 seconds of resting membrane potential recording (mean −55 mV) (blue trace) and compared to 50 shuffle surrogates (red traces). Black dashed line represents the 99.9% confidence interval for the 50 shuffle surrogates. (bottom) The same results are shown, but with regards to 90 seconds of recording at hyperpolarized membrane potential (mean −90 mV), from the same neuron. The PHRI values obtained from the hyperpolarized section of recording (bottom) were significantly greater than the PHRI values obtained from the resting membrane potential recording (top) (p<0.001, Kolmogorov-Smirnoff test).
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pone-0003983-g010: Effect of membrane potential hyperpolarization on PSP detection.(A) A sample of an in vivo current clamp recording is shown at an approximate resting membrane potential of −55 mV (top) versus a sample recorded from the same neuron minutes later at −95 mV (bottom). The hyperpolarized membrane potential was induced by a tonic DC injection. Underlined segments of these recordings are expanded in (B), showing the increased ability to detect smaller PSPs during hyperpolarized membrane potentials. (C) PHRI values recorded during resting membrane potential versus artificially induced hyperpolarized membrane potentials. (top) PHRI values are calculated from 90 seconds of resting membrane potential recording (mean −55 mV) (blue trace) and compared to 50 shuffle surrogates (red traces). Black dashed line represents the 99.9% confidence interval for the 50 shuffle surrogates. (bottom) The same results are shown, but with regards to 90 seconds of recording at hyperpolarized membrane potential (mean −90 mV), from the same neuron. The PHRI values obtained from the hyperpolarized section of recording (bottom) were significantly greater than the PHRI values obtained from the resting membrane potential recording (top) (p<0.001, Kolmogorov-Smirnoff test).

Mentions: Having convinced ourselves that some in vivo and in vitro recordings show evidence of significantly repeating patterns, we then addressed a previously discussed hypothesis: repeats of synaptic inputs are better detected during hyperpolarized membrane potentials. To this end, we recorded a neuron from mouse somatosensory cortex, in vivo, in current clamp at approximately −60 mV resting membrane potential, and then applied a DC hyperpolarizing current, bringing the membrane potential to approximately −90 mV. This particular recording allowed the identification of some PSPs at −60 mV, but PSPs appeared to be more easily detectable at −90 mV (Fig. 10A,B). Both HRI and PHRI analysis yielded significantly higher values for the −90 mV section of the recording versus the −60 mV section (p<0.01 Kolmogorov-Smirnoff tests for each analysis, 100 seconds of recording in −60 mV and −90 mV). Furthermore, when fifty 400 msec shuffled surrogates were created for each, the −90 mV section of the recording exceeded the distribution by a significantly greater margin, exceeding 99.9% confidence intervals (Fig. 10C).


Statistical significance of precisely repeated intracellular synaptic patterns.

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

Effect of membrane potential hyperpolarization on PSP detection.(A) A sample of an in vivo current clamp recording is shown at an approximate resting membrane potential of −55 mV (top) versus a sample recorded from the same neuron minutes later at −95 mV (bottom). The hyperpolarized membrane potential was induced by a tonic DC injection. Underlined segments of these recordings are expanded in (B), showing the increased ability to detect smaller PSPs during hyperpolarized membrane potentials. (C) PHRI values recorded during resting membrane potential versus artificially induced hyperpolarized membrane potentials. (top) PHRI values are calculated from 90 seconds of resting membrane potential recording (mean −55 mV) (blue trace) and compared to 50 shuffle surrogates (red traces). Black dashed line represents the 99.9% confidence interval for the 50 shuffle surrogates. (bottom) The same results are shown, but with regards to 90 seconds of recording at hyperpolarized membrane potential (mean −90 mV), from the same neuron. The PHRI values obtained from the hyperpolarized section of recording (bottom) were significantly greater than the PHRI values obtained from the resting membrane potential recording (top) (p<0.001, Kolmogorov-Smirnoff test).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003983-g010: Effect of membrane potential hyperpolarization on PSP detection.(A) A sample of an in vivo current clamp recording is shown at an approximate resting membrane potential of −55 mV (top) versus a sample recorded from the same neuron minutes later at −95 mV (bottom). The hyperpolarized membrane potential was induced by a tonic DC injection. Underlined segments of these recordings are expanded in (B), showing the increased ability to detect smaller PSPs during hyperpolarized membrane potentials. (C) PHRI values recorded during resting membrane potential versus artificially induced hyperpolarized membrane potentials. (top) PHRI values are calculated from 90 seconds of resting membrane potential recording (mean −55 mV) (blue trace) and compared to 50 shuffle surrogates (red traces). Black dashed line represents the 99.9% confidence interval for the 50 shuffle surrogates. (bottom) The same results are shown, but with regards to 90 seconds of recording at hyperpolarized membrane potential (mean −90 mV), from the same neuron. The PHRI values obtained from the hyperpolarized section of recording (bottom) were significantly greater than the PHRI values obtained from the resting membrane potential recording (top) (p<0.001, Kolmogorov-Smirnoff test).
Mentions: Having convinced ourselves that some in vivo and in vitro recordings show evidence of significantly repeating patterns, we then addressed a previously discussed hypothesis: repeats of synaptic inputs are better detected during hyperpolarized membrane potentials. To this end, we recorded a neuron from mouse somatosensory cortex, in vivo, in current clamp at approximately −60 mV resting membrane potential, and then applied a DC hyperpolarizing current, bringing the membrane potential to approximately −90 mV. This particular recording allowed the identification of some PSPs at −60 mV, but PSPs appeared to be more easily detectable at −90 mV (Fig. 10A,B). Both HRI and PHRI analysis yielded significantly higher values for the −90 mV section of the recording versus the −60 mV section (p<0.01 Kolmogorov-Smirnoff tests for each analysis, 100 seconds of recording in −60 mV and −90 mV). Furthermore, when fifty 400 msec shuffled surrogates were created for each, the −90 mV section of the recording exceeded the distribution by a significantly greater margin, exceeding 99.9% confidence intervals (Fig. 10C).

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