How neurons react to changes?
An intriguing feature of the nervous system is the plasticity, the lifelong amazing capacity to change and adapt in light of internal and external environmental modifications. This is the focus of our projects that are aimed at understanding this dynamic process of the vertebrate neural circuits controlling behavior. To achieve this goal, we need a thorough understanding of the organization of neural circuits underlying behavior. The overall aim of our research programs is to uncover the principles and functional consequences of plasticity under physiological and pathophysiological conditions.
To address this issue, we take advantage of the experimental amenability of the genetically powerful model system of the zebrafish – whose circuitry is relatively simple, better understood and produces a measurable and robust behavioral output.
Our multifaceted approach uses a comprehensive set of state-of-the-art techniques including functional imaging, electrophysiology, pharmacology, anatomy, molecular neuroscience and genetics. Such an effort is critical for the functional dissection of the neuronal classes and to understand their impact on circuits and behavior in health and disease.
Project 1: Adaptive phenomena in locomotor networks: Impact of plasticity mechanisms on neuromuscular disorders
Locomotion is a vital biological process for all animals including humans. An important role of the nervous system is the generation and control of locomotion for the effective navigation in the environment. Neuronal circuits within the spinal cord are able to produce a very diverse behavioral repertoire. Dysfunction of these circuits along with their target muscles is associated with neuromuscular disorders and injury. To restore motor function in injury or in disease, we first need to understand the organization of spinal circuits and second the plasticity mechanisms driving these phenotypes since these remain poorly understood. The focus here is to develop a causal understanding of how the spinal networks respond and adapt to physiological and pathophysiological conditions. The main objectives are:
- To reveal the molecular, electrophysiological and morphological changes of spinal cord neuronal populations associated with neuromuscular dysfunctions, injury, and exercise;
- To uncover changes in the anatomical and functional organization of the upstream spinal neurocircuitry;
- To identify the different pathways that generate and maintain the adaptive phenomena of spinal circuits;
- To restore the motor function in defect spinal networks.
The proposed front-line multidisciplinary approach uses state-of-the-art techniques from molecular neuroscience, genetics, optogenetics, and electrophysiology. Such an effort is ultimately necessary in order to translate circuit function and dysfunction in animal models to human neuromuscular disorders and injury. The long-term goal is to identify candidate neuronal populations and molecular targets for the design of novel therapeutic interventions, thus breaking new ground in this research field.
Project 2: What does the cerebellum really do?
All animals, like humans, are capable of a variety of coordinated body movements as part of their amazing behavioral repertoire. A converging line of evidence suggests that the cerebellum itself is the core of integrating not only motor-related information but also participates in numerous non-motor functions associated with cognition, emotions, and psychiatric illness. While a great deal is known regarding the structure, development and physiology of the cellular elements of the cerebellum, fundamental questions regarding its (dys)function remain unanswered. In the context of this research program, two critical questions arise. Does the cerebellum contribute to non-motor as to motor diseases? If so, how does altering its function contribute to such diverse symptoms? The architecture and connectivity of cerebellar circuits may hold the answers to these questions. In this project, we will try to elucidate the neuronal mechanisms by which the cerebellum integrates motor information, represents this input at cellular and synaptic level and orchestrates motor coordination in health and in pathophysiological motor and cognitive conditions.
“Adult spinal motoneurons change their neurotransmitter phenotype to control locomotion”
Maria Bertuzzi, Weipang Chang, Konstantinos Ampatzis
PNAS, online 1 October 2018, doi: 10.1073/pnas.1809050115
Complementary expression of calcium binding proteins delineates the functional organization of the locomotor network.
Brain Struct Funct 2018 Jun;223(5):2181-2196
Motor neurons control locomotor circuit function retrogradely via gap junctions.
Nature 2016 Jan;529(7586):399-402
Separate microcircuit modules of distinct v2a interneurons and motoneurons control the speed of locomotion.
Neuron 2014 Aug;83(4):934-43
Pattern of innervation and recruitment of different classes of motoneurons in adult zebrafish.
J. Neurosci. 2013 Jun;33(26):10875-86
Maria Bertuzzi - Postdoc
Weipang Chang - Postdoc
Pierre Fontanel - student
Andrea Pedroni - Postdoc
Fabjola Xheka - Student