Bistability of cerebellar Purkinje cells modulated by sensory stimulation

Abstract

A persistent change in neuronal activity after brief stimuli is a common feature of many neuronal microcircuits. This persistent activity can be sustained by ongoing reverberant network activity or by the intrinsic biophysical properties of individual cells. Here we demonstrate that rat and guinea pig cerebellar Purkinje cells in vivo show bistability of membrane potential and spike output on the time scale of seconds. The transition between membrane potential states can be bidirectionally triggered by the same brief current pulses. We also show that sensory activation of the climbing fiber input can switch Purkinje cells between the two states. The intrinsic nature of Purkinje cell bistability and its control by sensory input can be explained by a simple biophysical model. Purkinje cell bistability may have a key role in the short-term processing and storage of sensory information in the cerebellar cortex.

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Figure 1: Spontaneous membrane potential bistability in Purkinje cells in vivo.
Figure 2: Membrane potential bistability is a specific feature of Purkinje cells within the cerebellar cortex.
Figure 3: Membrane potential bistability is reflected in spike output pattern in vivo.
Figure 4: Intrinsic origin of membrane potential bistability in vivo.
Figure 5: Climbing fiber input can trigger transitions between states.
Figure 6: Characterization of the complex spike–induced transitions in vivo.
Figure 7: Sensory-evoked complex spikes in Purkinje cells can trigger membrane potential bistability in vivo.
Figure 8: A model for bistability and state transitions.

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Acknowledgements

We thank H. Meiri, E. Chorev and P. Mann-Metzer for excellent technical assistance, J.T. Davie for help with programming, and J.I. Simpson and T. Margrie for encouragement and helpful discussions. This work was supported by grants from the European Commission (M.H. and Y.Y.), Wellcome Trust (M.H and S.M), Gatsby Foundation (M.H), JSPS (K.K.), US-Israel BSF (Y.Y.), the Israel Science Foundation (Y.Y.), the Israel Science Foundation Center of Excellence 8006-00 (H.S.) and the Yeshaya Horowitz Association (Y.L.).

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Correspondence to Yonatan Loewenstein or Séverine Mahon.

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Supplementary information

Supplementary Fig. 1

Activation of h-current in cerebellar Purkinje cells in vivo. (PDF 520 kb)

Supplementary Fig. 2

A model of bistability demonstrates CF-evoked and spontaneous transitions. (PDF 263 kb)

Supplementary Note (PDF 115 kb)

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Loewenstein, Y., Mahon, S., Chadderton, P. et al. Bistability of cerebellar Purkinje cells modulated by sensory stimulation. Nat Neurosci 8, 202–211 (2005). https://doi.org/10.1038/nn1393

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