3DPLASTICITY · Plasticity of dendritic computations during active network states
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-02-01 → 2019-01-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Plasticity of dendritic computations during active network states
Overall objectives were to better understand how sensorimotor information is represented in the brain, study activity patterns generated by cortical pyramidal cells, and explore how plasticity may operate within networks to influence computations. Excitatory and inhibitory neurons form interconnected networks that extract sensorimotor features, combine them with internally generated evidence, and filter out irrelevant information, thereby creating perceptions and guiding behaviors. At the level of individual cells, information processing occurs at synaptic contacts all along their morphologically complex dendritic trees. It has been challenging to monitor this activity because most technologies lack the speed and agility to carry out stable in vivo recordings from small structures like dendrites. In addition, computations take place during various behavioral states in the context of the network. In vivo-like network activity patterns can dramatically alter how inputs are transformed into outputs, but how neurons actually process information in active networks in vivo is unclear. In addition, circuits are endowed with plasticity mechanisms that enable flexible adaptions to the environment. How plasticity impacts dendritic integration remains poorly defined. Resolving these issues will inform our mechanistic understanding of how single neurons process sensory information during naturalistic behaviors, enabling steps forward in our knowledge of normal brain function. Basic research impacts society by deepening our understanding of how the brain works. Complete explanations of how circuits operate should aid society in the long-run by leading to novel therapies that prevent or treat disease. There is an urgent need since the European Brain Council indicates 38% of the EU’s population (164.8 out of ~500 million people) suffer from mental disorders, which apparently amounts to 798 billion tax-payer euros. Unfortunately, it is difficult to design better treatments for mental disorders because the gap in our knowledge of how genetic and environmental factors affect proteins, synapses, neurons, and networks remains large.
Data: CORDIS, © European Union
Project objective
Neurons in the cortex generate sensory perceptions by extracting certain features from the environment and combining them with internally generated information. A better understanding of how neurons perform these computations will deepen our understanding of normal brain function and potentially identify novel therapies for mental conditions that perturb sensory perception such as autism, schizophrenia, and epilepsy. Neuronal computations occur at thousands of synapses across three dimensionally complex dendritic trees. In the cortex, dendritic integration takes place in the context of ongoing network activity, and recent work indicates that network activity profoundly alters how neurons compute sensory information. Yet, most of our current knowledge of how dendrites process synaptic inputs has been derived under non-physiological conditions, resulting in a poor understanding of network behavior in the living brain. An equally important property of cortical microcircuits is that they are endowed with a plethora of plasticity mechanisms that enable flexible adaptions to the environment. The role of synaptic plasticity at excitatory synapses is established for such adaptations. How inhibitory plasticity shapes dendritic integration and sensory processing remains largely unexplored. The purpose of my Marie Skłodowska-Curie Individual Fellowship is to elucidate how synaptic plasticity operates within active neuronal networks and how plasticity influences cortical computations within morphologically complex dendritic trees. To address these knowledge gaps, I will combine my expertise in synaptic plasticity, electrophysiology, and pharmacology with cutting-edge techniques I will learn under the mentorship of Professor Angus Silver including 3D imaging, optogenetic applications, and biologically detailed computer modelling. This cutting-edge training-through-research program is expected to transform our understanding of how single neurons compute sensory information.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union