For building a coherent view of our external world, the brain needs to integrate multiple types of sensory information coming from different sensory modalities such as vision, audition and somatosensation. The first cortical brain regions where these particular inputs are processed are the so called primary sensory cortices, the primary visual cortex (V1), the primary auditory cortex (A1) and the primary somatosensory cortex (S1). These specific cortical areas are organized topographically such that neurons with neighboring receptive fields get their input from neighboring locations in the outer world.
Traditionally, early sensory cortices were thought to be exclusively driven by their main sensory input. Recently however, this notion has been challenged as novel evidence shows that they can receive inputs originating from more than one sensory modality. The goal of this project is to understand the interplay between vision and somatosensation at the level of V1 and S1 in mice.
Experience-dependent changes of grey matter volume
It has been shown that training can lead to an increase of grey matter volume in the involved brain regions in humans and experimental animals. For example, a longitudinal MRI study could demonstrate that intense juggling training for 3 month or even for only 7 days leads to an expansion in grey matter in cortical visual motion areas. Likewise, expert London taxi drivers were shown to have a larger posterior hippocampal volume, a brain region which stores spatial representation of the spatial environment. Interestingly, high resolution MRI revealed that similar changes can be also detected in mice after spatial learning. However, neuroimaging measures do not provide information about the underlying biology of such changes. Hence, more detailed investigations, such as histological or in vivo two-photon imaging studies are required to make direct links between MRI measures and the precise underlying mechanisms. Identifying such links is the goal of this ambitious project. For this, we will first establish a behavioral protocol, which reliably induces an expansion of the involved cortical region in mice. Then, we will investigate the underlying structural changes in the cortex, which lead to such an expansion. For example, genesis and/or structural plasticity of non-neural cells, changes in neuronal morphology or vascular changes might be promising candidates because they are all supportive for increased neuronal function. A further highly important topic will be to examine the relative contribution of different cellular processes to the increase of cortical grey matter volume. Taken together, addressing these issues can provide novel insights into the microstructural mechanisms, which in turn lead to macrostructural changes of the cortex.
A fleeting experience can lead to the formation of an indelible memory. How is a transient experience stored as a long lasting memory trace in the brain? Could structural changes that occur after learning represent such a memory trace? Decades of research in different animal species suggests that they might. Long term but not short-term sensitization in the invertebrate Aplysia is associated with the formation of new synaptic structures. Chronic in vivo imaging in the mouse brain has shown that new spines rapidly form after a strong experience (e.g. monocular deprivation) or learning (e.g. auditory fear conditioning). Furthermore, new spine formation is restricted to behaviorally relevant brain areas, e.g. new spines form after monocular deprivation in the binocular but not monocular visual cortex. Strikingly, a subset of newly formed spines remain stable for months and are associated with the retention of a learned motor skill.
All these correlations point to ‘new spines’ playing an integral role in the storage of memory. Are these mere correlations or are ‘new spines’ causally involved in the storage of a recently encoded memory? Modern molecular and chemical genetic tools might finally allow us to answer these questions. We are working on developing and refining tools to selectively perturb the formation of or structural integrity of newly formed dendritic spines to study their role in learning and memory.
Structure, function and connectivity of layer 2/3 principal cells
Neocortical principal cells (PCs) are fundamental building blocks of the brain that display functional specializations defined by their connectivity as well as their molecular, anatomical, and electrophysiological properties. PCs in lower cortical layers are known to constitute distinct classes that can be distinguished based on their in vivo functional response properties, connectivity patterns, as well as genetic and electrophysiological characteristics. For PCs in layer 2/3 little is known about the detailed relationship between their stimulus-response properties and their cellular physiology and connectivity. We are now addressing this gap in knowledge by directly correlating the stimulus selectivity of individual layer 2/3 PCs in vivo with their morphological, electrophysiological, and connectivity signatures in vitro in the primary visual cortex of mice.
Functional binocular convergence in the retinogeniculate pathway
The dorsal lateral geniculate nucleus (dLGN) of the visual system is traditionally viewed as a simple relay station, where the activity of retinal ganglion cells is forwarded via parallel, eye-specific, and largely unmodified visual processing streams to primary visual cortex. However, thalamic cells have been recently reported to display binocular responses already at the level of the adult dLGN. We have established a dual colour optogenetic approach enabling us to functionally map cellular and subcellular inputs onto individual thalamic neurons in adult dLGN of mice to investigate the origin of these binocular responses.
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