The neuronal cortical network generates slow (<1Hz) spontaneous rhythmic activity that emerges from the recurrent connectivity. This activity occurs during slow wave sleep or anesthesia and also in cortical slices, consisting of alternating up (active, depolarized) and down (silent, hyperpolarized) states. The search for the underlying mechanisms and the possibility of analyzing network dynamics in vitro has been subject of numerous studies. This exposes the need for a detailed quantitative analysis of the membrane fluctuating behavior and computerized tools to automatically characterize the occurrence of up and down states.
Intracellular recordings from different areas of the cerebral cortex were obtained from both in vitro and in vivo preparations during slow oscillations. A method that separates up and down states recorded intracellularly is defined and analyzed here. The method exploits the crossover of moving averages, such that transitions between up and down membrane regimes can be anticipated based on recent and past voltage dynamics. We demonstrate experimentally the utility and performance of this method both offline and online, the online use allowing to trigger stimulation or other events in the desired period of the rhythm. This technique is compared with a histogram-based approach that separates the states by establishing one or two discriminating membrane potential levels. The robustness of the method presented here is tested on data that departs from highly regular alternating up and down states.
Applying this strategy to the characterization of the electrophysiological signal, the crossing points of the two EMAs are good approximations of the transitions between up and down states (of both, up and down initiation) (Fig. 1)
Offline separation of standard up and down states. Intracellular recording in vivo from a neuron in cat primary visual cortex. Time marks in the horizontal axes of the traces indicate 1 second interval. A fast EMA is represented as a black line and a slow EMA in dashed gray line. The points of crossing between both of them have been used to calculate the beginning and end of up states, highlighted with a blue box. (Seamari et al., PLoS ONE 2(9): e888)
This technique can be compared with a histogram-based approach that operates by establishing one or two discriminating membrane potential levels. The histogram-based approach cannot be applied reliably in any situation that differs from a highly regular oscillation, while the method we propose performs well on data that clearly departs from the standard picture, compensating for artifacts or conditions different from the ideal setting (Fig. 2 & 3.)
Offline up and down states separation in drifted recordings. In vivo intracellular recording from a neuron in the primary visual cortex from the cat. A drift in the membrane potential is illustrated. (Seamari et al., PLoS ONE 2(9): e888)
Histogram in drifted recordings. Histogram corresponding the Fig. 2. trace. (Seamari et al., PLoS ONE 2(9): e888)
This method can be used offline and also online (Mov. 1.), what allows triggering events upon the initiation of an up or down state. The method is simple in its definition and can be applied in real time on conventional computers for large amounts of data. An open-source MATLAB® toolbox, and Spike 2®-compatible version has been implemented. Below you can download the code in both languages.
Online detection of up and down states applying MAUDS to the intracellular recordings. Slow rhythm recorded in the barrel cortex of an anesthetized rat. Top panel: Online up states detection (trace going up), Middle panel: Unfiltered LFP. Bottom panel: Intracellular recording. (Seamari et al., PLoS ONE 2(9): e888)
Spike2 Script Version
In this version, the algorithm is written totally in the script language of spike2. The advantage is the legibility of the code. The algorithm is executed in the pc, sharing its resources with the task of recording the signals. So the delay of the characterization and real-time triggering depends on the pc used.
Spike2 Sequencer Version
In this version, the algorithm is implemented and executed into the sequencer of the data acquisition unit. The response time of this solution is very high and independent of the pc used. However, the code is much more unlegible because it is written in the assembler language of the sequencer.
Mauds implementation in Matlab. It can process mat data files and Spike2 txt exported files. Includes plotting utilities.
In the case of any question regarding our algorithms or our software, we provide a free forum to all interested scientists. Feel free to post any question or suggestion you might have.
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