title: A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.
abstract: The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.
authors.affiliation: 1 NeuroEngineering and Medical Robotics Laboratory, Department of Electronics, Information and Bioengineering, Politecnico di Milano, P.zza Leonardo Da Vinci 32, 20133, Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Geminiani
authors.affiliation: 1 NeuroEngineering and Medical Robotics Laboratory, Department of Electronics, Information and Bioengineering, Politecnico di Milano, P.zza Leonardo Da Vinci 32, 20133, Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Casellato
authors.affiliation: 1 NeuroEngineering and Medical Robotics Laboratory, Department of Electronics, Information and Bioengineering, Politecnico di Milano, P.zza Leonardo Da Vinci 32, 20133, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Antonietti
authors.affiliation: 2 Department of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, I-27100 Pavia, Italy.|3 Brain Connectivity Center, Istituto Neurologico, IRCCS Fondazione C. Mondino Via, Mondino 2, I-27100, Pavia, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: 4 Neuroengineering and Medical Robotics Laboratory, Department of Electronics, Information and Bioengineering, Politecnico di Milano, P.zza Leonardo Da Vinci 32, 20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pedrocchi
mesh_terms: D000200:Action Potentials; D000818:Animals; D002526:Cerebellar Diseases / Q000503:physiopathology*; D002531:Cerebellum / Q000293:injuries / Q000503:physiopathology*; D003198:Computer Simulation; D003215:Conditioning, Eyelid / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009434:Neural Pathways / Q000293:injuries / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology
keywords: Cerebellum; Spiking Neural Networks; eye blink conditioning; pathological models; synaptic plasticity