Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

Abstract

Climbing fiber-driven long-term depression (LTD) of parallel fiber synapses onto cerebellar Purkinje cells has long been investigated as a putative mechanism of motor learning. We recently discovered that the rules governing the induction of LTD at these synapses vary across different regions of the cerebellum. Here, we discuss the design of LTD induction protocols in light of this heterogeneity in plasticity rules. The analytical advantages of the cerebellum provide an opportunity to develop a deeper understanding of how the specific plasticity rules at synapses support the implementation of learning.

World Statistics Drive Learning of Cerebellar Internal Models in Adaptive Feedback Control: A Case Study Using the Optokinetic Reflex

“…We observed instability in the learning rule when the PF signal was not delayed, similarly to Yamamoto et al (2002). Evidence for a delayed error signal (∼120 ms) has come from studies of cerebellar long-term depression (Suvrathan et al, 2016;Suvrathan and Raymond, 2018), which show that this delay occurs in the flocculus that deals with the OKR, while other delays are found elsewhere in the cerebellum.…”

Cerebellar learning using perturbations

“…Thus, keeping synaptic inhibition intact has long been recognised as being of potential importance, with debates regarding its role in hippocampal LTP dating back decades ( Wigström and Gustafsson, 1983a ; Wigström and Gustafsson, 1983b ; Arima-Yoshida et al, 2011 ). Very recent work also highlights the importance of inhibition in the induction of cerebellar plasticity ( Rowan et al, 2018 ; Suvrathan and Raymond, 2018 ).…”

Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development

“…A key role of retrograde eCB signaling from PCs to PFs has been implicated in both cerebellar LTD (Safo and Regehr 2005) and DSE (Kreitzer and Regehr 2001;Tanimura, Kawata et al 2009). However, spike timing parameters required for PF LTD vary significantly between the vermis and other cerebellar regions (Suvrathan, Payne et al 2016), leading to a proposal that heterogenous (cannabinoid dependent and independent) mechanisms may contribute to PF plasticity in the vermal versus non-vermal cerebellar regions (Crepel 2007;Suvrathan and Raymond 2018). Our results, highlighting a spatially restricted pattern of CB1 expression in developing PFs during the first two postnatal weeks, offer molecular basis in support of the hypothesis that PF plasticity in hemispheres and nodular zones may be less dependent on eCB signaling than in the anterior and central vermis.…”