PURPOSE: Recent evidence supports the importance of action potential bursts in physiological neural coding, as well as in pathological epileptogenesis. To better understand the temporal dynamics of neuronal input currents that trigger burst firing, we characterized spectral patterns of stimulation current that generate bursts of action potentials from regularly spiking neocortical neurons in vitro. METHODS: Sharp microelectrodes were used for intracellular recording and stimulation of cortical neurons in rat brain slices. Quasi-white-noise (0-2 kHz) and "chirp" sine wave currents of decreasing wavelength were applied to represent a broad spectrum of stimulation frequencies. Action potential-related averaging of the stimulation current variations preceding bursting was used to characterize stimulation current patterns more likely to result in a burst rather than a single-spike response. RESULTS: Bursts of action potentials were most reliably generated by a preceding series of > or = 2 positive current transients at 164+/-37 Hz of the quasi-white-noise, and to sine wave currents with frequencies greater than 90 Hz. The intraburst action potential rate was linearly related to the frequency of the input sine wave current. CONCLUSIONS: This study demonstrates that regularly spiking cortical neurons in vitro burst in response to fast oscillations of input currents. In the presence of positive cortical feedback loops, encoding input frequency in the intraburst action potential rate may be safer than producing a high-frequency regular output spike train. This leads to the experimentally testable and therapeutically important hypothesis that burst firing could be an antiepileptogenic and/or anti-ictogenic mechanism.
PURPOSE: Recent evidence supports the importance of action potential bursts in physiological neural coding, as well as in pathological epileptogenesis. To better understand the temporal dynamics of neuronal input currents that trigger burst firing, we characterized spectral patterns of stimulation current that generate bursts of action potentials from regularly spiking neocortical neurons in vitro. METHODS: Sharp microelectrodes were used for intracellular recording and stimulation of cortical neurons in rat brain slices. Quasi-white-noise (0-2 kHz) and "chirp" sine wave currents of decreasing wavelength were applied to represent a broad spectrum of stimulation frequencies. Action potential-related averaging of the stimulation current variations preceding bursting was used to characterize stimulation current patterns more likely to result in a burst rather than a single-spike response. RESULTS: Bursts of action potentials were most reliably generated by a preceding series of > or = 2 positive current transients at 164+/-37 Hz of the quasi-white-noise, and to sine wave currents with frequencies greater than 90 Hz. The intraburst action potential rate was linearly related to the frequency of the input sine wave current. CONCLUSIONS: This study demonstrates that regularly spiking cortical neurons in vitro burst in response to fast oscillations of input currents. In the presence of positive cortical feedback loops, encoding input frequency in the intraburst action potential rate may be safer than producing a high-frequency regular output spike train. This leads to the experimentally testable and therapeutically important hypothesis that burst firing could be an antiepileptogenic and/or anti-ictogenic mechanism.
Authors: Dina Simkin; Kelly A Marshall; Carlos G Vanoye; Reshma R Desai; Bernabe I Bustos; Brandon N Piyevsky; Juan A Ortega; Marc Forrest; Gabriella L Robertson; Peter Penzes; Linda C Laux; Steven J Lubbe; John J Millichap; Alfred L George; Evangelos Kiskinis Journal: Elife Date: 2021-02-05 Impact factor: 8.713