一般口演（Oral）

Oral Cerebellum 一般口演小脳

7月25日（木）16:50～17:05　第9会場（朱鷺メッセ　3F　306+307） 1O-09e1-1 Specific learning deficit associated with selective impairments of excitability modulation dependent on SK2 channels in cerebellar Purkinje cells Giorgio Grasselli（Grasselli Giorgio）^1,4，Henk-Jan Boele（Boele Henk-Jan）²，Heather K. Titley（Titley Heather K.）¹，Nora Bradford（Bradford Nora）¹，Lisa van Beers（van Beers Lisa）²，Lindsey Jay（Jay Lindsey）¹，Chris I. De Zeeuw（De Zeeuw Chris I.）^2,3，Martijn Schonewille（Schonewille Martijn）²，Christian Hansel（Hansel Christian）¹ ¹Department of Neurobiology, The University of Chicago, Chicago, IL, USA ²Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands ³Netherlands Institute for Neuroscience, Royal Academy of Sciences (KNAW), Amsterdam, The Netherlands ⁴Center for Synaptic Neuroscience and Technology (NSYN), Istituto Italiano di Tecnologia (IIT), Genova, Italy Currently, prevailing theories of learning and memory are based on synaptic plasticity as the main underlying cellular mechanism (long-term potentiation and depression, i.e. LTP and LTD, respectively). However, a growing body of evidence suggests that synaptic plasticity might be complemented by other forms of neuronal plasticity, such as activity-dependent changes in membrane excitability (`intrinsic plasticity'). What remains controversial is the question whether intrinsic plasticity actually plays a relevant role in learning and memory independent from synaptic plasticity. In order to directly test this hypothesis, we report a new conditional knock-out mouse for SK2, the calcium-gated potassium channel that mediates intrinsic plasticity in cerebellar Purkinje cells (its downregulation is responsible for their activity-dependent increase of excitability). We used this new mouse line to generate a Purkinje cell-specific SK2 knock-out mouse (L7-SK2). These mice show Purkinje cell morphology and density comparable to control littermates. Intrinsic plasticity is absent from these mice, but no alterations were found in synaptic transmission and plasticity at parallel fiber-to-Purkinje cell synapses (both LTD and LTP). We observed a selective impairment in delay eyeblink conditioning, an associative learning paradigm known to require an intact cerebellum and modulation of the simple spike activity. We also found a moderate alteration in the pattern of locomotion of these mice, namely a significant increase in step length and, accordingly, a decrease in frequency. However, we did not find signs of general ataxia, or changes in other types of motor behaviors, such as motor performance on the rotarod, or eye movement-related motor behaviors as tested in the optokinetic response (OKR), the vestibulo-ocular reflex (VOR), or the visually enhanced vestibulo-ocular reflex (VVOR). Importantly, we also did not find significant alterations in VOR gain-increase adaptation, which is another major paradigm for testing cerebellar learning. These results indicate that a purely non-synaptic, SK2-dependent mechanism of neuronal plasticity is necessary for specific forms of cerebellar learning by contributing to the encoding of memories.		7月25日（木）17:05～17:20　第9会場（朱鷺メッセ　3F　306+307） 1O-09e1-2 小脳登上線維シグナルによる自発的レバー引き運動の表現 Naoki Hidaka（日高直樹）^1,2，Koji Ikezoe（池添貢司）¹，Shinichiro Tsutsumi（堤新一郎）²，Yoshikazu Isomura（磯村宜和）³，Masanobu Kano（狩野方伸）²，Kazuo Kitamura（喜多村和郎）^1,2 ¹山梨大院医工神経生理 ²東京大院医神経生理 ³玉川大脳研 In the cerebellar neuronal network, the Purkinje cell (PC) is the sole output of the cerebellar cortex, which receives excitatory inputs from thousands of parallel fibers and a single climbing fiber (CF). The classical theory postulates that CFs encode motor errors, however, ample evidence suggests the CFs' encording of diverse information other than errors, including movement kinematics. Furthermore, it is still unclear how population CF signals represent information of voluntary movements that is required for the online control of movements. To address these issues, we performed in vivo two-photon calcium imaging in mice during voluntary forelimb lever-pull task, and investigated the relationship between the activity of population CF signals and the lever-pull movements. Mice were trained to pull and hold (>400 ms) mechanical cantilever voluntarily to obtain water reward (4-8 μl). Since Ca²⁺ transients in PC dendrites in vivo have been shown to reflect complex spikes, i.e., CF responses, we expressed genetically-encoded calcium indicator into PCs using AAV, and observed fluorescence changes in PC dendrites located in the forelimb area of lobule V of the cerebellar vermis. We observed Ca²⁺ transients correlated with forelimb movements in most of PCs observed, and found three types of activity patterns: 1) large and transient increase at the onset of lever-pull movement, 2) persistent activity during lever-holding period, 3) suppression of activity during lever-pull and -holding period. We also found that many cells were tuned to parameters of the lever movement (position, speed, and acceleration). These results suggest that activity patterns of cerebellar CFs represent the information about forelimb movements, and encode specific parameters related to lever movements. Therefore, it is possible that the combination of these distinct types of PCs, which converge on deep cerebellar nuclei neurons, could fully represent actual motor commands or trajectories for forelimb movements.

7月25日（木）17:20～17:35　第9会場（朱鷺メッセ　3F　306+307） 1O-09e1-3 Cognitive learning related changes in activity profiles of mid-lateral cerebellar Purkinje cells Naveen Sendhilnathan（Sendhilnathan Naveen），Michael Goldberg（Goldberg Michael） Columbia University How do we learn to establish associations between arbitrary visual cues (like a red light) and movements (like braking the car)? There is a growing consensus that cognitive learning requires a distributed network that includes the PFC, basal ganglia and the mid-lateral cerebellum. Although the cerebellum has been primarily considered to have roles in motor coordination, recent clinical, anatomical and electrophysiological evidence suggest a cognitive role. Therefore, we investigated the neural correlates of visuomotor association learning in the monkey mid-lateral cerebellum. Learning a novel visuomotor association involves associating an arbitrary symbol with a particular movement even though there is nothing about that symbol that describes the movement it instructs, as a red traffic light instructs a driver to press the brake. The error signal is cognitive in nature and does not describe a mistake in the parameters of the movement, but rather it describes the consequence of failing to make the association. Here we show that, during learning but not when the associations were overlearned, individual Purkinje cells (P-cells) reported the outcome of the monkey's most recent decision, a cognitive error signal, which was independent of changes in hand movement or reaction time. At the population level, P-cells collectively maintained a memory of the most recent decision throughout the entire trial period, updating it after every decision. This cognitive error signal decreased as the performance improved. Surprisingly, despite this decrease in cognitive error signal, the neural activity profiles of P-cells showed learning related changes even after learning. Firstly, all the P-cells changed their activity profile at the switch from overlearned to novel learning and continued to change their activity profile dynamically learning. However, while the activity profile of a subset of P-cells returned to the baseline level after learning, the activity profile of remaining P-cells did not. Therefore, at the end of learning, the activity profile was heterogeneous across the population of P-cells. This indicates a mechanism of synaptic weight changes that led to cognitive learning. Taken together, our results argue towards a broader role of cerebellum and gather evidence that, rather than being regarded just as a motor control system, it could be a generalized control system, essential in motor as well as cognitive adaptation and rule learning.		7月25日（木）17:35～17:50　第9会場（朱鷺メッセ　3F　306+307） 1O-09e1-4 Coupling-induced synchronization controls degree-of-freedoms in cerebellar learning Huu Thien Hoang（Hoang Thien Huu）¹，Eric Lang（Lang Eric）²，Yoshito Hirarta（Hirarta Yoshito）³，Isao Tokuda（Tokuda Isao）⁴，Kazuyuki Aihara（Aihara Kazuyuki）³，Keisuke Toyama（Toyama Keisuke）¹，Mitsuo Kawato（Kawato Mitsuo）¹，Nicolas Schweighofer（Schweighofer Nicolas）⁵ ¹ATR脳情報通信総合研脳情報研神経情報 ²Department of Neuroscience and Physiology, New York University School of Medicine ³Institute of Industrial Science, The University of Tokyo ⁴Department of Mechanical Engineering, Ritsumeikan University ⁵Biokinesiology and Physical Therapy, University of Southern California Information theory suggests that the degree-of-freedoms in learning systems should be proportionally compatible with the number of training samples to avoid "overfitting". Then how does the cerebellum with a huge degree-of-freedoms learn from a small set of training samples while also being constrained by low firing frequency of the inferior olive neurons, the origin of its teaching signals? Combining in-vivo spiking data of inferior olive neurons with a novel modeling approach, we found that increased electrical coupling via gap-junctions between inferior olive neurons induces synchronous activity and decreases the dimensionality of firing dynamics. We postulate that this mechanism can be realized, in parallel with other possible mechanisms, to optimally control the degree-of-freedoms in the cerebellum during learning. Early in learning, strong coupling strength between inferior olive neurons induces strong and widespread synchrony to decrease the degree-of-freedoms, results in fast but coarse learning. As the learning proceeds, the coupling strength is gradually decreased via feedback loops from the cerebellar cortex to maximize the degree-of-freedoms, results in sophisticated learning. This strategy may allow the cerebellum to learn effectively from a small training sample set despite the low firing frequency of inferior olive neurons.