Neuromodulation, such as that associated with paying attention, changes the way our brains interpret our sensory experiences. Understanding the neuromodulation of neural circuitry that integrates and processes incoming sensory input to generate a meaningful output remains a fundamental question in neuroscience. While the neuromodulator acetylcholine is shown to enhance sensory responses, the cellular mechanisms by which it mediates these effects are still poorly understood. Recent evidence suggests that the local subthreshold dendritic potentials, dendritic spikes, which are important in synaptic input integration, also play a key role in encoding feature selectivity, the ability of neurons in sensory cortices to be tuned to specific features of a stimulus. Interestingly, ion channels, such as potassium channels that regulate dendritic spikes are also shown to be modulated by cholinergic inputs. Here, I propose that acetylcholine modulates sensory processing via modulation of dendritic spikes. I will use a combination of state-of-the-art in vivo imaging, electrophysiology, pharmacology and optogenetics to test the novel hypothesis that acetylcholine modulates sensory processing by regulating dendritic spikes and thereby feature selectivity in mouse somatosensory cortex. The project will provide new cellular insights into a long-standing question on the mechanisms of neuromodulation of sensory processing. It builds on my expertise in neuroanatomy and physiology and will give me the opportunity to master advanced in vivo techniques in a host environment that is well known for their in vivo expertise and research into neuromodulation. Given my strong background in neurodevelopmental disorders, the project will push the knowledge frontier on neuronal processing and will provide a framework for research into basic mechanisms of sensory perception and their alterations in neurological disorders.
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