Using animal models to unravel cerebellar tDCS mechanisms in humans

Symposium title: New perspectives on cerebellar plasticity: from basic research to the clinic Symposium description: The cerebellum and its related networks present one of the main neuronal circuits in the brain and its dysfunction can lead to a wide range of neurological disorders. In recent years non-invasive brain stimulation (NIBS) techniques have been used in animal models and humans to modulate cerebellar excitability gaining insight into underlying mechanisms of cerebellar-sensorimotor loops and their involvement in behavior, but also to better understand clinical models of cerebellar dysfunction. Thus, the main aim of the present symposium proposal is to integrate different approaches to expand our knowledge of modulating cerebellar-related processes through the use of NIBS as well as to investigate changes of cerebellar and cortical excitability in clinical models. Firstly, we will unravel cerebellum-related mechanisms through the use of cerebellar direct-current transcranial stimulation (tDCS) in a mouse model. The obtained knowledge from the animal brain will enhance our understanding of the mechanisms of NIBS in the healthy human brain and is essential for the development of effective strategies to improve tDCS effects in the cerebellum. To optimize the outcomes of the application of NIBS to the human cerebellum it is also crucial to develop new methodological approaches that aim to target specific cerebellar mechanisms, which will be the second focus of this proposal. We will explore cerebellar plasticity and related effects induced by two novel techniques in healthy humans. Specifically paired somatosensory-cerebellar stimulation (c-PAS) and cerebellar alternating current stimulation (tACS). Finally, integrating the acquired knowledge on the normal functioning of cerebellar-related processes by the use of the mentioned approaches can help us to decipher the changes we observe in cerebello-thalamo-cortical plasticity assessed through different transcranial magnetic stimulation (TMS) protocols in a clinical model such as essential tremor. The present symposium proposal includes gender, geographic, and age-into-career diversity, as well as diversity in the technologies examined. Abstract Cerebellar tDCS (Cb-tDCS) has been demonstrated to modulate motor, cognitive and emotional behaviors, relaying on different cerebellar neural substrates and being proposed as a noninvasive neuromodulatory therapy for treating cerebellum-related disorders. However, the precise mechanisms underlying these effects are partially unknown. Understanding how externally applied currents affect neuronal spiking activity in cerebellar circuits becomes essential to develop new strategies to optimize the effects of tDCS in humans. During the last years, animal models have played a key role in elucidating the mechanisms mediating tDCS effects defining safety limits, inspiring new stimulation protocols, enhancing brain function, validating computational models, and exploring new therapeutic applications. Interestingly, the mice cerebellum constitutes an excellent experimental model to study the impact of tDCS in vivo at a microscale level presenting a highly convoluted cortex similar to humans, with electrophysiologically-identifiable Purkinje cell (by recording complex and simple spike firing) being the only output from cerebellar cortex. In this presentation, we will summarize recent results from our laboratory about the impact of Cb-tDCS on cerebellar circuitry, sensory processing and cerebellar to brain inhibition phenomena in awake animals. These results could be crucial for micro and mesoscale models pointing out the importance of considering the neuronal orientation to predict final immediate tDCS effects in the cerebral and cerebellar cortex. These findings could also contribute to optimize desired Cb-tDCS effects in different cerebellum-related disorders. Research Category and Technology and Methods Translational Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: cerebellum, neuromodulation, tDCS, mice