CBBS Best Paper of The Year 2021

CBBS spokesperson Prof. Dr. med. Stefan Remy, Prof. Dr. med. Emrah Düzel and Prof. Dr. Toemme Noesselt, together with the Rector of the OVGU, present the certificates and cheques to the award winners. Photos: Blumenstein/LIN

Antibiotic-induced gut dysbiosis leads to activation of microglia and impairment of cholinergic gamma oscillations in the hippocampus

Antibiotics are being prescribed to treat bacterial infections for decades and have saved countless lives since their discovery almost 100 years ago. However, experimental findings from preclinical rodent models have provided convincing evidence for the potentially negative impact of antibiotics on cognitive and emotional behaviour. Such behavioural abnormalities have been linked to aberrant gut microbiota-to-brain signalling (gut-brain axis) triggered by depletion of microbiota (dysbiosis) in the gastrointestinal tract. Thus, understanding the impact of gut dysbiosis induced by prolonged antibiotic treatment on immune function and brain physiology are of high clinical relevance to establish alternative strategies such as probiotics / prebiotics to restore gut microbiota composition and associated behavioural and physiological changes. In this work, we provide evidence for an altered expression pattern for several cytokines and neurotrophins that can potentially alter hippocampal physiology. We further show that prolonged antibiotic treatment induces an activated phenotype of microglia, a non-neuronal cell type that is gaining interest in the context of sustainment of hippocampal synaptic transmission and gamma oscillations in pathological conditions. We substantiate these findings via elucidating a strong reduction in baseline synaptic transmission and cholinergic gamma oscillations in the hippocampus. To the best of our knowledge, our work is the first to show the impact of prolonged antibiotic use on behaviorally-relevant network oscillations and synaptic physiology in the hippocampus, a brain region that plays a fundamental role in innate and cognitive behavior. Together, our study provides new insights into the interaction of gut microbiota, immune system and hippocampal function and lay the foundation for future intervention strategies for treatment of gut dysbiosis associated pathologies.

The organizational principles of de-differentiated topographic maps in somatosensory cortex

Topographic maps are a fundamental feature of cortex architecture in the mammalian brain. Their malfunctions can give rise to a multitude of sensory, motor, and cognitive functions and associated deficits. One common theory is that brain ageing leads to the ‘de-differentiation’ of topographic maps, which can be conceptualised as greater map activation, larger map area, more noisy units and/or less cortical inhibition between neighbouring units. Moreover the de-differentiation process was assumed to underlie maladaptive behaviour. With the combination of ultra-high resolution 7T functional magnetic resonance imaging (7T-fMRI) of human primary somatosensory cortex (S1) topographic maps, computational modelling, psychophysics, and everyday sensory and motor task assessments, we disproved this theory. We found that older adults do not show greater map activation or larger map areas, but show larger population receptive field sizes (i.e., the cumulative response of a population of neurons within a fMRI voxel), more overlapping neighbouring sensory representations but less similar distant representations, and reduced cortical distance (i.e., the distance between finger representations) between index finger and middle finger representations in S1. Given the latter was related to worse finger individuation but better motor performance, the present work uncovers the drawbacks of a simple de-differentiation model of topographic map function, and motivates the introduction of feature-based models of cortical reorganisation. This does not only allow us to investigate human sensory ageing more comprehensively, but also help us better understand age-related changes in topographic map architectures and their behavioural correlates.