Experience-induced synaptic plasticity and network activity in visual cortex

We have investigated how sensory information is processed and encoded into memories in the brain. There exists different kinds of learning involving different brain areas. Common for all is that learning induce lasting structural and functional changes in the contacts between neurons. In the project, we took advantage of how easy animals learn and remembers associations between a neutral and an unpleasant stimuli. In combination with these behavioral experiments we use genetic tools to perturbate and map the neural circuitry involved and directly assess the underlying neural activity by use of advanced recording technologies. In the first published work we revealed molecular mechanisms for long term storage of such associations. This work received much attention when it was published in prestigious Proceedings of the National Academy of Sciences earlier last year. We are now publishing work with experiments in which we mapped the neuronal networks in the brain that are responsible for different types of fear responses in rats. Here we combined genetic manipulation (optogenetics) with behavioral studies, immunohistochemistry and imaging. We also established a learning task for mice which will allow imaging of large neuron populations during the learning process. The brain areas involved in fear memories are part of the evolutionary old brain regions that is conserved throughout the animal kingdom all the way to humans. This makes the insights from the projects potentially important to increase our understanding of mechanisms underlying mental disease such as anxiety, depression and post-traumatic stress disorders in humans. The work from the project was part of three PhD dissertations at UiO.

Prosjektet omfattet grunnforskning for å forstå hvordan hjernen lærer og hvilke nevrale og molekylære mekanismer som bidrar til dette. To postdoktorer var ansatt i prosjektet. Den ene av disse har jobb i annen sektor mens den andre har valgt å forfølge en karriere i akademia. Postdoktorene erhvervet er ny kompetanse som var viktig for deres utvikling. I tillegg bygger prosjektleders forskningsgruppe videre på de teknikker og kompetanse som ble etablert i prosjektet. Postdoktorene fikk medveilederansvar for tre PhD kandidater som jobbet på komplementære prosjekter og på den måten bidro til prosjektgjennomføringen. Veilederkompetansen er viktig for kvalifisering til toppstillinger i akademia. Internasjonale samarbeid ble introdusert i forbindelse med prosjektet. Disse videreføres nå i andre NFR støttede prosjekter til prosjektleder som Toppforsk. Forskningsresultatene og de nye samarbeidene danner også grunnlag for planlagte søknader fra prosjektleder til NFR og ERC (CoG 2021).

The way in which we perceive the world is highly influenced by previous experiences and the state of mind. The response properties of neurons in primary sensory cortices remain malleable throughout life and the existence of such plasticity and the charact eristics of a form of implicit learning known as perceptual learning suggest that changes in primary sensory cortex may mediate learning. While much knowledge a of sensory systems has been garnered from animals under deep anesthesia, the state that is mos t inimical to new learning, the next step in neuroscience is to study cortical processing in awake and behaving animals. I propose to identify the neural fingerprint that reflects learning of sensory experiences in cortical circuits from structural change s of synapses to changes in the population code of neural ensembles in behaving animals. To achieve this, I will make use of advanced techniques such as large-scale electrophysiological recordings, two-photon laser-scanning microscopy, and genetic tools f or celltype-specific genetic interference. We will induce activity-dependent plasticity experimentally through learning the animals to associate salient cues the and directly assess the effects of these processes on synapse dynamics and network activity i n visual cortex. The research outcome will identify mechanisms underlying basic cortical plasticity and function that will have great impact on our understanding of normal brain function and help our understanding of what fails in the diseased brain. The outcome of these experiments on behaving animals will open an avenue of directions on which I will pursues my future research to untangle how experience modifies cortical circuits to form long-lasting memories.