Abstract
Key points: Ventrolateral thalamus (VL) integrates information from cerebellar nuclei and motor cortical layer VI. Inputs from the cerebellar nuclei evoke large-amplitude responses that depress upon repetitive stimulation while layer VI inputs from motor cortex induce small-amplitude facilitating responses. We report that the spiking of VL neurons can be determined by the thalamic membrane potential, the frequency of cerebellar inputs and the duration of pauses after cerebellar high frequency stimulation. Inputs from motor cortical layer VI shift the VL membrane potential and modulate the VL spike output in response to cerebellar stimulation. These results help us to decipher how the cerebellar output is integrated in VL and modulated by motor cortical input. Abstract: Orchestrating complex movements requires well-timed interaction of cerebellar, thalamic and cerebral structures, but the mechanisms underlying the integration of cerebro-cerebellar information in motor thalamus remain largely unknown. Here we investigated how excitatory inputs from cerebellar nuclei (CN) and primary motor cortex layer VI (M1-L6) neurons may regulate the activity of neurons in the mouse ventrolateral (VL) thalamus. Using dual-optical stimulation of the CN and M1-L6 axons and in vitro whole-cell recordings of the responses in VL neurons, we studied the individual responses as well as the effects of combined CN and M1-L6 stimulation. Whereas CN inputs evoked large-amplitude responses that were depressed upon repetitive stimulation, M1-L6 inputs elicited small-amplitude responses that were facilitated upon repetitive stimulation. Moreover, pauses in CN stimuli could directly affect VL spiking probability, an effect that was modulated by VL membrane potential. When CN and M1-L6 pathways were co-activated, motor cortical afferents increased the thalamic spike output in response to cerebellar stimulation, indicating that CN and M1 synergistically, yet differentially, control the membrane potential and spiking pattern of VL neurons.
| Original language | English |
|---|---|
| Pages (from-to) | 2055-2073 |
| Number of pages | 19 |
| Journal | Journal of Physiology-London |
| Volume | 599 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1 Apr 2021 |
Bibliographical note
Funding Information:C.B.S. and F.E.H. are supported by the Dutch organization for life sciences (NWO‐ALW; VIDI grant No. 016.121.346) and Medical Sciences (TOP‐GO No. 91210067). Z.G. is supported by the Dutch organization for life sciences (NWO‐ALM; VENI grant No. 863.14.001 and NWO‐CAS grant No. 012.200.14) and the Erasmus MC fellowship. C.I.D.Z. thanks the Dutch Organization for Medical Sciences (Zon‐MW; TOP‐GO No. 91210067), Life Sciences (ALW; No. 854.10.004), ERC‐adv (No. 294775), ERC‐POC (No. 768914) and LISTEN (No. 6) of the EU, as well as Medical NeuroDelta (No. 7) for support. In addition the authors are funded by the Dutch Organization for Medical Sciences (ZonMw), Life Sciences (ALW‐ENW‐Klein), the European Research Council (Advanced and Proof of Concept grants), the EU LISTEN Innovative Training Network programme, the Medical NeuroDelta programme, LSH‐NWO (Crossover, INTENSE), Albinism Vriendenfonds NIN, van Raamsdonk fonds, and the Trustfonds of Erasmus University, Rotterdam. None of the funding bodies had any input to the study design or outcome.
Publisher Copyright:
© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society