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Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice

Nature Neuroscience volume 18, pages 1798–1803 (2015)Cite this article

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Abstract

Climbing fiber inputs to Purkinje cells are thought to be involved in generating the instructive signals that drive cerebellar learning. To investigate how these instructive signals are encoded, we recorded the activity of individual climbing fibers during cerebellum-dependent eyeblink conditioning in mice. We found that climbing fibers signaled both the unexpected delivery and the unexpected omission of the periocular airpuff that served as the instructive signal for eyeblink conditioning. In addition, we observed that climbing fibers activated by periocular airpuffs also responded to stimuli from other sensory modalities if those stimuli were novel or if they predicted that the periocular airpuff was about to be presented. This pattern of climbing fiber activity is markedly similar to the responses of dopamine neurons during reinforcement learning, which have been shown to encode a particular type of instructive signal known as a temporal difference prediction error.

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Figure 1: Experimental design and approach.
Figure 2: Climbing fiber responses in the US period.
Figure 3: Climbing fiber responses in the CS period.
Figure 4: Complex spikes in CS period are not driven by eyelid movement.
Figure 5: Climbing fiber responses to novel stimuli.

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Acknowledgements

We thank K. Ohmae for technical support and S. Heiney for help with analysis and neurophysiological approach. This work was supported by a grant to J.F.M. from the US National Institutes of Health (R01 MH093727), and a grant to S.O. from Japan Society for the Promotion of Science (Grant-in-Aid for JSPS Fellows) and from the Uehara Memorial Foundation.

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Authors and Affiliations

  1. Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA

    Shogo Ohmae & Javier F Medina

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  1. Shogo Ohmae
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Contributions

S.O. and J.F.M. designed the research plan. S.O. performed all of the experiments and analyzed data. J.F.M. and S.O. prepared the figures and wrote the manuscript.

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Correspondence to Javier F Medina.

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Integrated supplementary information

Supplementary Figure 1 Examples of Cspk responses during habituation and differential conditioning

(a,b) Eyelid traces (Mean and standard deviation) and Cspk responses to the CS– in 2 representative Purkinje cells of a naïve mouse during habituation. (c) Time course of Cspk response to the CS– over multiple sessions of habituation (one Purkinje cell per session). The 2 Purkinje cells in (a,b) are indicated by arrows. Stimulus selectivity of the Cspk response was computed for each cell as (RPuff – RLED)/(RPuff + RLED) where RPuff and RLED are the baseline subtracted Cspk responses to the unexpected airpuff and LED stimuli respectively. An index value of 0 indicates the Cspk response to the Puff and LED were equal, whereas values of 1 and -1 indicate the Cspk response was selective for the Puff or the LED respectively. (d–i) Same format as (a–c) for representative Purkinje cells of a mouse trained in differential conditioning with an LED stimulus as the CS+ and a Tone stimulus as the CS– (d–f), and for a different mouse trained with Tone as the CS+ and LED as the CS– (g–i). In f,i stimulus selectivity of the Cspk response was computed for each cell as (RTone – RLED)/(RTone + RLED). An index value of 0 indicates the Cspk response to the Tone and LED were equal, whereas values of 1 and -1 indicate the Cspk response was selective for the Tone or the LED respectively. (c,f,i) Pearson’s correlation coefficients indicate that there was a significant reduction of Cspk responses to the CS– over the course of multiple training sessions in the three mice.

Supplementary Figure 2 Analysis of novelty signals in different recording sessions

Probability of Cspk response to the CS– in the first 2 and last 2 recording sessions (a–c), or in the first 5 and the last 5 recording sessions (d–f). Conventions are as in Figure 5e–g. The number of points for each plot comes from pooling the data across all mice and taking into account all the available Cspk responses to the tone and to the LED CS– in the corresponding habituation and differential conditioning sessions. Note that the CS– triggered a Cspk with high probability in the first few but not in the last few recording sessions, regardless of whether the analysis was based on comparing the first 2 and the last 2 sessions (a–c), the first 3 and the last 3 sessions (Fig. 5e–g), or the first 5 and the last 5 sessions (d–f).

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Ohmae, S., Medina, J. Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice. Nat Neurosci 18, 1798–1803 (2015). https://doi.org/10.1038/nn.4167

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