Final Report Summary - IN VIVO PLASTICITY (Neuronal circuits and synaptic mechanisms of experience-dependent plasticity)
I have started my research group in 2013 at the University of Edinburgh, after my post-doctoral training at the Technical University Munich, Germany. The global aim of the group is to understand how brain neuronal networks represent the outside world and how experience modifies the activity of such networks. I am using the mouse primary visual cortex, as a model system of cortical integration in health and disease.
During the first 2 years of the Career Integration Grant (CIG), I have established my independent research group at the Centre for Discovery Brain Sciences, University of Edinburgh. I applied and was awarded a prestigious Sir Henry Dale Fellowship from the Wellcome Trust for 5 years. I have established a key imaging infrastructure for my laboratory and have recruited 2 PhD students and a post-doctoral fellow. My research group has implemented the method of chronic two-photon calcium imaging that allows monitoring the activity of hundreds of neurons during several weeks in awake behaving mice. The analysis of these big imaging data set is computationally intensive. I have established collaborations with the School of Informatics of the University of Edinburgh to implement analysis tools and, as a result, the lab has developed and published an analysis toolbox for calcium imaging data (Keemink et al., Scientific report, 2018).
Using this approach, the first project of the lab has revealed how locomotion modulates the activity of excitatory and sub-types of inhibitory neurons in the visual cortex (Pakan et al., eLife, 2016). These findings established that modulation of neuronal activity by locomotion is context-dependent and cell-type specific. This significant progress in establishing the context-dependent responses of inhibitory neurons allowed further investigation of whether and how these context-dependent responses are modified by experience. In order to reveal how experience modifies the activity of neuronal networks in the adult brain, we are imaging the activity of neuronal sub-populations (excitatory and inhibitory) during the learning of a behavioural task. For this, we have adapted a virtual reality environment to the two-photon set-up.
The results obtained in healthy animals are used as a reference to probe potential deficits in neuronal population activity in the cortex of two mouse models of autistic spectrum disorders and intellectual disabilities: Fragile X (Fmr1-/y), the most widespread single-gene cause of autism and a mouse model of intellectual disability, namely a heterozygous null mutation in Syngap.
Impact of the project
The results of this project were presented at national and international conferences (at least three per year) as well as during invited lectures. The resulting articles were published in international peer-reviewed scientific journals.
The results of this project contributed to the understanding of the mechanisms underlying sensory cortical function and plasticity. Knowing how cortical responses are modified by experience will suggest possible strategies to promote functional recovery, for example to increase the impact of perceptual learning for the recovery of visual function after stroke or after traumatic brain injury. Increasing our understanding about facilitating perceptual learning will become even more critical in the coming years when biotechnologies for visual aids and hearing aids, such as cochlear implants, come into wider use. For these technologies to be effective will require conditions that maximize brain plasticity for efficient integration and correct perception.
I have been involved in several outreach activities including:
- the Explorathon 2014, 2015 and 2016 ‘Meet the experts’, EU researchers night. Collaboration with Dr Hennig (School of Informatics), ‘From the eye to the brain: How do you see the world?’ Demonstrations and discussions with the public at the National Museum of Scotland.
- Science Insights work experience, research taster sessions, visit and demonstrations in the lab for high school pupils, 2015, 2016
- Participation in the outreach programs for the general public and the families of autistic and intellectually disabled patients organized by the Patrick Wild Centre.
During the first 2 years of the Career Integration Grant (CIG), I have established my independent research group at the Centre for Discovery Brain Sciences, University of Edinburgh. I applied and was awarded a prestigious Sir Henry Dale Fellowship from the Wellcome Trust for 5 years. I have established a key imaging infrastructure for my laboratory and have recruited 2 PhD students and a post-doctoral fellow. My research group has implemented the method of chronic two-photon calcium imaging that allows monitoring the activity of hundreds of neurons during several weeks in awake behaving mice. The analysis of these big imaging data set is computationally intensive. I have established collaborations with the School of Informatics of the University of Edinburgh to implement analysis tools and, as a result, the lab has developed and published an analysis toolbox for calcium imaging data (Keemink et al., Scientific report, 2018).
Using this approach, the first project of the lab has revealed how locomotion modulates the activity of excitatory and sub-types of inhibitory neurons in the visual cortex (Pakan et al., eLife, 2016). These findings established that modulation of neuronal activity by locomotion is context-dependent and cell-type specific. This significant progress in establishing the context-dependent responses of inhibitory neurons allowed further investigation of whether and how these context-dependent responses are modified by experience. In order to reveal how experience modifies the activity of neuronal networks in the adult brain, we are imaging the activity of neuronal sub-populations (excitatory and inhibitory) during the learning of a behavioural task. For this, we have adapted a virtual reality environment to the two-photon set-up.
The results obtained in healthy animals are used as a reference to probe potential deficits in neuronal population activity in the cortex of two mouse models of autistic spectrum disorders and intellectual disabilities: Fragile X (Fmr1-/y), the most widespread single-gene cause of autism and a mouse model of intellectual disability, namely a heterozygous null mutation in Syngap.
Impact of the project
The results of this project were presented at national and international conferences (at least three per year) as well as during invited lectures. The resulting articles were published in international peer-reviewed scientific journals.
The results of this project contributed to the understanding of the mechanisms underlying sensory cortical function and plasticity. Knowing how cortical responses are modified by experience will suggest possible strategies to promote functional recovery, for example to increase the impact of perceptual learning for the recovery of visual function after stroke or after traumatic brain injury. Increasing our understanding about facilitating perceptual learning will become even more critical in the coming years when biotechnologies for visual aids and hearing aids, such as cochlear implants, come into wider use. For these technologies to be effective will require conditions that maximize brain plasticity for efficient integration and correct perception.
I have been involved in several outreach activities including:
- the Explorathon 2014, 2015 and 2016 ‘Meet the experts’, EU researchers night. Collaboration with Dr Hennig (School of Informatics), ‘From the eye to the brain: How do you see the world?’ Demonstrations and discussions with the public at the National Museum of Scotland.
- Science Insights work experience, research taster sessions, visit and demonstrations in the lab for high school pupils, 2015, 2016
- Participation in the outreach programs for the general public and the families of autistic and intellectually disabled patients organized by the Patrick Wild Centre.