Cerebellar Potentiation and Learning a Whisker-Based Object Localization Task with a Time Response Window

Abstract

Whisker-based object localization requires activation and plasticity of somatosensory and motor cortex. These parts of the cerebral cortex receive strong projections from the cerebellum via the thalamus, but it is unclear whether and to what extent cerebellar processing may contribute to such a sensorimotor task. Here, we subjected knock-out mice, which suffer from impaired intrinsic plasticity in their Purkinje cells and long-term potentiation at their parallel fiber-to-Purkinje cell synapses (L7-PP2B), to an object localization task with a time response window (RW). Water-deprived animals had to learn to localize an object with their whiskers, and based upon this location they were trained to lick within a particular period ("go" trial) or refrain from licking ("no-go" trial). L7-PP2B mice were not ataxic and showed proper basic motor performance during whisking and licking, but were severely impaired in learning this task compared with wild-type littermates. Significantly fewer L7-PP2B mice were able to learn the task at long RWs. Those L7-PP2B mice that eventually learned the task made unstable progress, were significantly slower in learning, and showed deficiencies in temporal tuning. These differences became greater as the RW became narrower. Trained wild-type mice, but not L7-PP2B mice, showed a net increase in simple spikes and complex spikes of their Purkinje cells during the task. We conclude that cerebellar processing, and potentiation in particular, can contribute to learning a whisker-based object localization task when timing is relevant. This study points toward a relevant role of cerebellum-cerebrum interaction in a sophisticated cognitive task requiring strict temporal processing.

Motor Learning and the Cerebellum

“…4) and eyeblink conditioning (Fig. 6), but probably also for more complex, timing-sensitive processes involved in cognition and episodic memory formation (Ben-Yakov and Dudai 2011; Rahmati et al 2014 (Galliano et al 2013b), but the very same mutants start to show phenotypes in decision making when tight temporal response windows are inserted in go/nogo tasks (Rahmati et al 2014). Likewise, the timing function of the olivocerebellar system is essential when acute reflexes need to be engaged following perturbations (Van Der Giessen et al 2008).…”

“…Over the past decades, it has gradually become clear that each module is concerned with control of specific tasks, such as execution of limb and finger movements, of trunk movements for balance, of compensatory eye movements about particular axes in space, reflexes of facial musculature, homeostasis of particular autonomic processes, and probably even specific cognitive tasks, such as time-sensitive decision making (De Zeeuw et al 1994;Ito 2008;Jörntell et al 2000;Apps and Hawkes 2009;Rahmati et al 2014). However, it was not until recently that the specific intrinsic properties of different categories of modules emerged (Zhou et al 2014).…”

Chronic imaging of movement-related Purkinje cell calcium activity in awake behaving mice

“…However, the importance of these signals as it relates to behavior or learning the task is not clear and may not relate to learning the pole discrimination task at all. However, it is possible that these signals help enforce proper timing of the task, including reward licking (Rahmati et al 2014). Moving forward, combining the ability to chronically image Ca 2ϩ with optogenetic control of the inferior olive should allow for both disruption of the lick-based Ca 2ϩ events and monitoring of the resulting behavior.…”

The anatomy of fear learning in the cerebellum: A systematic meta-analysis

“…LTP in these areas is assumed to be related to the consolidation of fear memories (Gao et al, 2012), akin to the function of an LTP mechanism that takes place in amygdala and hippocampus (Bliss and Collingridge, 2013;Rogan et al, 1997;Sacchetti et al, 2001). However, a recent study in cerebellar mouse mutants has shown that impairments in Purkinje cell plasticity did not affect fear responses during Page 5 of 38 A c c e p t e d M a n u s c r i p t 5 both cued and contextual conditioning (Galliano et al, 2013), even though it did result in learning deficits when a cognitive task with temporal constraints was employed (Rahmati et al, 2014). These results suggest that the cerebellum is essentially concerned with tasks requiring precise temporal accuracy (Rahmati et al, 2014;Yamaguchi and Sakurai, 2014).…”

“…Furthermore, many fear learning paradigms involve sensorimotor and timing components next to emotional learning (Glickstein et al, 2009;Rahmati et al, 2014), thus further obfuscating the investigation into the primary role of the cerebellar regions in the purely emotional, non-motor aspects of the fear learning process. As a result, a decisive account of the precise regions and Page 6 of 38 A c c e p t e d M a n u s c r i p t 6 functional contribution of the cerebellum involved in human fear learning remains to be determined.…”