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Self–sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABAA receptor potentials

Abstract

Intracellular recordings from reticular thalamic (RE) neurons in vivo revealed inhibitory postsynaptic potentials (IPSPs) between RE cells that reversed and became depolarizing at the hyperpolarized membrane potentials that occur during sleep. These excitatory IPSPs can directly trigger low–threshold spikes (LTSs). The oscillatory mechanisms underlying IPSP–triggered LTSs crowned by spike bursts were investigated in models of isolated RE networks. In a one–dimensional network model, external stimulation evoked waves of excitation propagating at a constant velocity of 25–150 cells per second. In a large–scale, two–dimensional model of the reticular nucleus, the network showed transient or self–sustained oscillations controlled by the maximum conductance of the low–threshold calcium current and the membrane potential. This model predicts that the isolated reticular nucleus could initiate sequences of spindle oscillations in thalamocortical networks in vivo.

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Figure 1: Reversed IPSP in an RE neuron in vivo directly triggers a low–threshold spike (LTS).
Figure 2: Spontaneous activity of RE neurons in vivo is characterized by spindle activity interspersed with low–frequency ( 2 Hz) spike bursts.
Figure 3: Spontaneous activity of RE neurons.
Figure 4: Response of a model RE cell stimulated by a 5–Hz train of GABAA receptor IPSPs at different levels of membrane potential.
Figure 5: Localized pattern of activity propagating through the model of an isolated RE network.
Figure 6: Velocity of the traveling wave as a function of GABAA receptor coupling strength and radius of RE–RE connections in a one–dimensional RE network model.
Figure 7: Localized patterns of activity in a two–dimensional network model of 50 × 50 RE cells (x– and y–axes) with flow boundary conditions.
Figure 8: The influence of the membrane potential on the frequency of oscillations in a two–dimensional network model with 33 × 33 RE cells.

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Acknowledgements

This research was supported by the Howard Hughes Medical Institute, the Sloan Center for Theoretical Neurobiology, the Human Frontier Science Program and the Medical Research Council of Canada.

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Bazhenov, M., Timofeev, I., Steriade, M. et al. Self–sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABAA receptor potentials. Nat Neurosci 2, 168–174 (1999). https://doi.org/10.1038/5729

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