Grey matter sublayer thickness estimation in the mouse cerebellum

The cerebellar grey matter morphology is an important feature to study neurodegenerative diseases such as Alzheimer’s disease or Down’s syndrome. Its volume or thickness is commonly used as a surrogate imaging biomarker for such diseases. Most studies about grey matter thickness estimation focused on the cortex, and little attention has been drawn on the morphology of the cerebellum. Using ex vivo highresolution MRI, it is now possible to visualise the different cell layers in the mouse cerebellum. In this work, we introduce a framework to extract the Purkinje layer within the grey matter, enabling the estimation of the thickness of the cerebellar grey matter, the granular layer and molecular layer from gadolinium-enhanced ex vivo mouse brain MRI. Application to mouse model of Down’s syndrome found reduced cortical and layer thicknesses in the transchromosomic group

Drift and stabilization of cortical response selectivity

Synaptic turnover and long term functional stability are two seemingly contradicting features of neuronal networks, which show varying expressions across different brain regions. Recent studies have shown, how both of these are strongly expressed in the hippocampus, raising the question how this can be reconciled within a biological network. In this work, I use a data set of neuron activity from mice behaving within a virtual environment recorded over up to several months to extend and develop methods, showing how the activity of hundreds of neurons per individual animal can be reliably tracked and characterized. I employ these methods to analyze network- and individual neuron behavior during the initial formation of a place map from the activity of individual place cells while the animal learns to navigate in a new environment, as well as during the condition of a constant environment over several weeks. In a published study included in this work, we find that map formation is driven by selective stabilization of place cells coding for salient regions, with distinct characteristics for neurons coding for landmark, reward, or other locations. Strikingly, we find that in mice lacking Shank2, an autism spectrum disorder (ASD)-linked gene encoding an excitatory postsynaptic scaffold protein, a characteristic overrepresentation of visual landmarks is missing while the overrepresentation of reward location remains intact, suggesting different underlying mechanisms in the stabilization. In the condition of a constant environment, I find how turnover dynamics largely decouple from the location of a place field and are governed by a strong decorrelation of population activity on short time scales (hours to days), followed by long-lasting correlations (days to months) above chance level. In agreement with earlier studies, I find a slow, constant drift in the population of active neurons, while – contrary to earlier results – place fields within the active population are assumed approximately randomly. Place field movement across days is governed by periods of stability around an anchor position, interrupted by random, long-range relocation. The data does not suggest the existence of populations of neurons showing distinct properties of stability, but rather shows a continuous range from highly unstable to very stable functional- and non-functional activity. Average timescales of reliable contributions to the neural code are on the order of few days, in agreement with earlier reported timescales of synaptic turnover in the hippocampus.2021-08-0