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Scientific Fields
Diseases
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Applications
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Starting Date
01
Jan 2017
Ending Date
01
Feb 2036
Status
Ongoing
Members
5
Structures
1

About

Synaptic representation of multisensory information

The GC layer of the CC is thought to pre-process incoming mossy fiber (MF) activity so that PCs can more easily distinguish distinct patterns associated specific sensory contexts. The precise combination of internal and external sensory cues indicates a sensory motor state that is then “learned” by association with a feedback signal (supervised learning), in order to fine tune motor movements and cognitive functions. But how the input-specific properties of MF-GC synapses that we recently identified contribute to multisensory stimulus representation and CC computations is not known.

In contrast to our previous work in the vestibular cerebellum, we propose to examine the diversity of synaptic strength and STP in lateral cerebellum, a region thought to influence cognitive behaviors. We will use clustering algorithms to identify the various classes of synapse strengths and dynamics from patch-clamp recordings in brain slices. MF pathway-specific synaptic behaviors will be determined for visual, auditory, whisker, and pontine pathways (similar to Chabrol et al. 2015).

In vivo detection of synaptic transmission will be detected using sparse GC expression of a genetically encoded fluorescence glutamate sensor (Figure 1, Marvin et al. 2018). All synaptic inputs of a single GC, as well as its output, will be monitored in awake mice using high-speed random access 2-photon imaging.

Figure 1.  iGluSnFr responses in granule cell axons from cerebellar brain slices.

Completed projects:

Chabrol, F.P., Arenz, A., Wiechert, M.T., Margrie, T.W., and DiGregorio, D.A. (2015). Synaptic diversity enables temporal coding of coincident multisensory inputs in single neurons. Nature Neuroscience 18, 718-727.

Summary:  Synaptic strength and dynamics is diverse across synapse types, however it is not known how circuits might take advantage of this diversity for specific computations.  In this study we demonstrated that synaptic response diversity reflects the diversity of sensory information entering the cerebellum, and enables a novel temporal coding scheme for multisensory inputs (Chabrol et al., 2015).

Figure 2. Multimodal convergence onto single GCs. (a) Double labeling of primary (1°) and secondary (2°) vestibular afferents, or primary vestibular and visual afferents. AAV9-TurboRFP (magenta) was injected in MVe or PrH of transgenic animals (Thy1-mGFP; green). (b) Example two-photon laser scanning microscopy images of fluorescent MFs in lobule X. (c) Example whole-cell patched GCs filled with Alexa 594 (white) that were found to be connected to VG and MVe or VG and PrH MFs (stars). (d) z-projection of three-dimensional reconstructions of the connected GCs and MFs shown in c.
Figure 3. (d) patch-clamp voltage responses of single GCs evoked from individual and simultaneous stimulation of supporting (G4 (visual)) and driver MF inputs (G1, 2 (Primary vestibular) and 5 (secondary vestibular)). Early EPSP summation expanded from boxed region (right column) demonstrates combination-specific delays akin to those obtained with single driver MF input stimulation without baseline tonic activity (see a). (e) Comparison of GC firing rates when driven by single inputs (G1, 2, 5 and 3; n = 4, 3, 3 and 5 cells, respectively) versus when combined with input group 4 (or, in one case (square symbol), group 3). Red curve indicates a line with unity slope. (f) Summary plot of combination-specific first-spike latencies.