Dynamics of the Cortico-Cerebellar Loop Fine-Tune Dexterous Movement

Abstract

These authors contributed equally. SummaryCerebral cortex and cerebellum are thought to interact bidirectionally during movement, motor planning, Pavlovian conditioning, and cognitive function. The pontine nuclei (PN), which consist of the basal pontine nuclei and the reticulotegmental nucleus, constitute the principal hub that convey descending signals from higher brain areas into the cerebellum. The PN receive a massive input from layer 5 of nearly the entire ipsilateral cerebral cortex, and they are thought to serve as a relatively simple relay of this information to both the cerebellar cortex and cerebellar nuclei. Although PN neurons occupy an important anatomical position, little is known about their firing properties during natural movement, feedback effects on cortical activity, or functional role in behavior. Here, we use electrophysiological recordings along with optogenetic and pharmacogenetic perturbations to reveal three key aspects of PN function. First, during the execution of a cortically-dependent reach-to-grab behavior, many PN neurons respond to the movement or to non-motor events, such as the cue signaling trial start. Some neurons respond to both motor and non-motor events, suggesting that the PN do not simply relay separate channels of information into cerebellum, but perform multimodal integration. Second, motor cortical neurons that receive feedback from the ponto-cerebellar system have distinct functional properties during behavior. Third, perturbations of PN function impair performance of reaching, disrupt limb kinematics, and alter the functional responses of motor cortical neurons during movement. Taken together, these results demonstrate that the PN are a rich integrative hub that are essential for dexterous motor control.

Thalamic control of cortical dynamics in a model of flexible motor sequencing

“…Furthermore, sensory feedback is absent in our model. In many realistic settings, sensory feedback is likely to be key in organizing the sequence, as well as in providing error-correcting information (Penhune and Steele, 2012;Guo et al, 2020;Dacre et al, 2019). Our thalamocortical model could be extended by introducing a cerebellar module, which could fine-tune cortical dynamics in response to sensory feedback and/or contribute to motif selection and tuning.…”

Convergence of proprioceptive and visual feedback on neurons in primary motor cortex

“…Primary motor cortex (M1) plays an important role in generating goal-directed corrections during motor actions. M1 receives rich sensory inputs from many brain regions involved in proprioceptive and visual processing including the parietal and frontal cortices (Jones et al, 1978; Zarzecki and Strick, 1978; Crammond and Kalaska, 1989; Porter and Lemon, 1993; Buneo et al, 2002; Pesaran et al, 2006; McGuire and Sabes, 2011; Bremner and Andersen, 2012; Dea et al, 2016; Omrani et al, 2016; Gamberini et al, 2017; Piserchia et al, 2017; Kalidindi et al, 2020; Takei et al, 2021), as well as input from cerebellum (Conrad et al, 1975; Vilis et al, 1976; Strick, 1983; Guo et al, 2020; Sauerbrei et al, 2020). M1 rapidly responds to proprioceptive feedback of the limb within ∼20-40ms of an applied mechanical load (Evarts and Tanji, 1976; Wolpaw, 1980; Lemon, 1981a; Suminski et al, 2009; Pruszynski et al, 2011, 2014; Omrani et al, 2014; Heming et al, 2019) and to visual feedback of the limb and goal within ∼70ms (Georgopoulos et al, 1983; Cisek and Kalaska, 2005; Ames et al, 2014; Stavisky et al, 2017).…”

The Mesodiencephalic Junction as a Central Hub for Cerebro-Cerebellar Communication

“…When considering how the CC may influence cerebellar activity, the first major hub that comes to mind is the pons, which is the main source of mossy fibres for the cerebellum (Henschke and Pakan, 2020, Coffman et al, 2011, Ruigrok, 2004). The pons receives prominent topographic projections from a wide variety of cortical regions (Leergaard, 2003, Leergaard et al, 2000, Wiesendanger and Wiesendanger, 1982) and has been shown to exert a powerful control over the lateral hemispheres of the cerebellar cortex and dentate nucleus during various types of behaviours, including planning and coordination of limb and eye movements (Guo et al, 2020, Chabrol et al, 2019, Ohmae et al, 2017). Here, we show unique topographic projections from the CC to the cerebellar cortex via the MDJ and IO, providing the climbing fibres to the Purkinje cells in the cerebellum.…”

“…Instead, information flow from the CC to the cerebellum is massively relayed via the pontine nuclei (Legg et al, 1989, Glickstein et al, 1985, Leergaard, 2003, Brodal, 1978). The ponto-cerebellar connection provides mossy fibres to the granule cells in the cerebellar cortex and collaterals to neurons in the CN (Henschke and Pakan, 2020, Biswas et al, 2019, Ruigrok, 2011), which is instrumental in planning and coordinating fine precision movements of the forelimbs (Wagner et al, 2019, Guo et al, 2020).…”