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Multimodal sensory integration in single cerebellar granule cells in vivo

  1. Taro Ishikawa
  2. Misa Shimuta
  3. Michael Häusser  Is a corresponding author
  1. University College London, United Kingdom
  2. Jikei University School of Medicine, Japan
Research Advance
Cite this article as: eLife 2015;4:e12916 doi: 10.7554/eLife.12916
4 figures


Figure 1 with 3 supplements
EPSCs evoked by activation of different sensory modalities in cerebellar granule cells in vivo.

(A–F) Representative recordings from three different granule cells are presented for each modality. EPSCs were evoked by somatosensory stimulation (air puff to whiskers), auditory stimulation (white noise 89 dB) or visual stimulation (white LED, ipsilateral eye) recorded under voltage clamp at -70 mV. The bars above the traces indicate the timing of stimulation and the vertical dotted lines indicate the onset of the stimulation. The timescale is common for all panels A–E and is indicated at the bottom of panel E. (A) Four consecutive traces for each type of stimulation. (B) Raster plots of EPSC events. (C) Time histograms of EPSCs; bin width is 25 ms. (D) Cumulative time histograms (baseline subtracted). (E) The amplitudes of all EPSCs are plotted. (F–G) Pie charts indicating the total numbers of multimodal, unimodal and nonresponsive cells recorded in the crus I and II area (133 cells) and the dorsal paraflocculus (30 cells). Characters indicate the types of stimulation (S, somatosensory; A, auditory; V, visual), to which the cells responded. Cells that responded to multiple sensory modalities were indicated by the combination of those characters (A & S, S & V, A & V and A & S & V).

Figure 1—figure supplement 1
Dependence of auditory responses of granule cells on sound levels (white noise).

The event number (A) increases with sound level while the mean EPSC amplitude (B) remains constant. Different symbols indicate different cells (n = 4).

Figure 1—figure supplement 2
The ipsilateral visual response was predominant over the contralateral response, as measured by the EPSC event number (A), the total synaptic charge (B) and the latency (C) evoked by visual stimulation by binocular LEDs (10 cells).

(D) The mean EPSC amplitude was not different between the three types of stimulation (ANOVA).

Figure 1—figure supplement 3
Table summarizing the properties of EPSCs evoked by unisensory stimulation.
Figure 2 with 1 supplement
Single granule cells exhibit multi-sensory responses.

EPSCs evoked by multi-sensory stimulation in a single cerebellar granule cell in crus II. EPSCs were evoked by somatosensory stimulation (air puff to whiskers), auditory stimulation (white noise, 91 dB) or a combination of the two. Trials were interleaved with an inter-trial interval of 3 s under voltage clamp at -70 mV. The color bars at the top indicate duration of stimuli, and the vertical dotted lines indicate the onset of the stimulation. The time scale is common for panels AE and indicated at the bottom of E. (A) Four consecutive traces for each type of stimulation. (B) Raster plots of EPSC events. (C) Time histograms of EPSCs; bin width is 25 ms. The linearity index was calculated as the event number evoked by the combined stimulation divided by the sum of those evoked by the two unimodal stimulations. (D) Cumulative time histograms (baseline subtracted). (E) Amplitudes of all EPSCs. (F) Cumulative distribution of the amplitudes of the first events in a burst of evoked EPSCs. The amplitudes were significantly different between the two modalities (P < 0.05). Inset, average traces of first EPSCs. (G–H) Comparison of the amplitudes of EPSCs evoked by different sensory modalities. For each multimodal cell, the amplitudes of first-evoked EPSCs (mean ± s.e.m.) in response to two sensory modalities are plotted against each other. Eight out of 20 cells (16 in crus I and II [G] and 4 in dorsal paraflocculus [H]) had significantly different amplitudes (P < 0.05, indicated by red marks) and deviate from the unity line (dotted line).

Figure 2—figure supplement 1
EPSC event numbers (AB) and latencies (CD) of the sensory responses of individual multimodal granule cells.

Red symbols indicate the same cells labeled red in Figure 2G–H. Even though the number of EPSC events and the latency differed between sensory modalities in some cells, we did not use these characteristics to judge if the granule cells had separate mossy fiber inputs or not because these parameters are affected by not only synaptic properties of individual mossy fiber terminals but also upstream signaling systems that control the firing pattern of neurons projecting the mossy fibers.

Multisensory integration can enhance granule cell output.

(AC) Action potentials in a representative granule cell evoked by multisensory stimulation. EPSPs and action potentials were evoked by somatosensory stimulation, auditory stimulation and combination of these two. Trials were interleaved with an inter-trial interval of 3 s. The granule cell was current-clamped with no bias current. The color bars at the top indicate the duration of stimulation and the vertical dotted lines indicate the onset of stimulation. (A) Representative traces are expanded to show evoked EPSPs and action potentials. Ten consecutive traces are overlaid. The peaks of action potentials are truncated. (B) All recorded traces are shown with the time scale indicated at the bottom of panel C. (C) Time histograms of evoked action potentials. The bin width is 25 ms. (D) Input-output relationships for 4 granule cells. The number of action potentials evoked in current-clamp mode was plotted against synaptic charge measured in voltage-clamp mode. The spike numbers are baseline-subtracted. Values from the same granule cell are connected by lines. Blue circles indicate the response to somatosensory stimulation, red circles auditory stimulation, purple circles combined somatosensory and auditory stimulation. The cell shown in A–C corresponds to Cell 1 in D.

Functional configurations of multisensory integration at the mossy fiber–granule cell connection.

Schematic diagrams showing potential anatomical substrates of the different multisensory integration scenarios described in the results. (A) Multimodal signals are transmitted by separate pathways and converge onto a single granule cell. (B) A single mossy fiber conveys mixed multi-modal signals. (C) Multimodal signals converge onto a granule cell, but the two pathways interact. In these schematics, the round cells represent pre-cerebellar neurons whose axons form mossy fibers. The triangular cells represent neurons projecting to the pre-cerebellar neurons (e.g. cortical neurons projecting to pontine neurons). Gray diamond-shaped neurons represent hypothetical interneurons. Another possibility for interaction between two separate pathways (not illustrated here) is presynaptic inhibition (Mitchell and Silver, 2000) or postsynaptic inhibition (Duguid et al., 2015) via Golgi cells.


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