Odor processing in the lateral entorhinal cortex revealed by two-photon calcium imaging

Recent studies ascribed to the lateral entorhinal cortex (LEC) an important function in object recognition and novelty detection and confirmed the involvement of the LEC in odor processing. In this thesis, I investigated the contribution of LEC layer II neurons in sensory processing. Using immunohistochemical staining methods I could show that excitatory neurons in LEC layer II can be distinguished based on the expression of two marker proteins, namely Reelin and calbindin (CB). In combination with retrograde tracer injections, I revealed distinct projection patterns of these two excitatory cell types, with Reelin+ neurons projecting to the hippocampus and CB+ neurons providing feedback to structures of the olfactory system. Inhibitory GABAergic neurons in layer II of the LEC comprise a variety of molecularly defined subtypes. My goal was to analyze the participation of the defined cell classes in stimulus-triggered network activity. Therefore, I implemented in vivo two-photon imaging of genetically encoded calcium indicators in the LEC of anesthetized mice. This approach allowed me to investigate the activity of small neuronal networks in response to olfactory stimulation. I demonstrated that Reelin+ excitatory neurons transmitting information directly to the hippocampus respond with high selectivity to different odors. A markedly less selective response profile is exhibited by excitatory CB+ neurons that convey feedback to upstream targets in the olfactory pathway. It was possible to contrast these response patterns of excitatory neurons with that of their inhibitory counterparts. Thus, GABAergic neurons responded the least selective to various odors. Furthermore, we established in vivo whole-cell patch-clamp recordings under visual guidance. This enabled us to particularly target excitatory and GABAergic odor-responsive cells and to characterize them based on electrophysiological and morphological criteria. In summary, I defined and characterized here different neuronal subtypes in the LEC that are functionally involved in the processing and transmission of odor information

Untangling perceptual memory: hysteresis and adaptation map into separate cortical networks

Perception is an active inferential process in which prior knowledge is combined with sensory input, the result of which determines the contents of awareness. Accordingly, previous experience is known to help the brain “decide” what to perceive. However, a critical aspect that has not been addressed is that previous experience can exert 2 opposing effects on perception: An attractive effect, sensitizing the brain to perceive the same again (hysteresis), or a repulsive effect, making it more likely to perceive something else (adaptation). We used functional magnetic resonance imaging and modeling to elucidate how the brain entertains these 2 opposing processes, and what determines the direction of such experience-dependent perceptual effects. We found that although affecting our perception concurrently, hysteresis and adaptation map into distinct cortical networks: a widespread network of higher-order visual and fronto-parietal areas was involved in perceptual stabilization, while adaptation was confined to early visual areas. This areal and hierarchical segregation may explain how the brain maintains the balance between exploiting redundancies and staying sensitive to new information. We provide a Bayesian model that accounts for the coexistence of hysteresis and adaptation by separating their causes into 2 distinct terms: Hysteresis alters the prior, whereas adaptation changes the sensory evidence (the likelihood function)

Untangling Perceptual Memory: Hysteresis and Adaptation Map into Separate Cortical Networks

Perception is an active inferential process in which prior knowledge is combined with sensory input, the result of which determines the contents of awareness. Accordingly, previous experience is known to help the brain "decide” what to perceive. However, a critical aspect that has not been addressed is that previous experience can exert 2 opposing effects on perception: An attractive effect, sensitizing the brain to perceive the same again (hysteresis), or a repulsive effect, making it more likely to perceive something else (adaptation). We used functional magnetic resonance imaging and modeling to elucidate how the brain entertains these 2 opposing processes, and what determines the direction of such experience-dependent perceptual effects. We found that although affecting our perception concurrently, hysteresis and adaptation map into distinct cortical networks: a widespread network of higher-order visual and fronto-parietal areas was involved in perceptual stabilization, while adaptation was confined to early visual areas. This areal and hierarchical segregation may explain how the brain maintains the balance between exploiting redundancies and staying sensitive to new information. We provide a Bayesian model that accounts for the coexistence of hysteresis and adaptation by separating their causes into 2 distinct terms: Hysteresis alters the prior, whereas adaptation changes the sensory evidence (the likelihood function

Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex

The lateral entorhinal cortex (LEC) computes and transfers olfactory information from the olfactory bulb to the hippocampus. Here we established LEC connectivity to upstream and downstream brain regions to understand how the LEC processes olfactory information. We report that, in layer II (LII), reelin- and calbindin-positive (RE(+) and CB(+)) neurons constitute two major excitatory cell types that are electrophysiologically distinct and differentially connected. RE(+) neurons convey information to the hippocampus, while CB(+) neurons project to the olfactory cortex and the olfactory bulb. In vivo calcium imaging revealed that RE(+) neurons responded with higher selectivity to specific odors than CB(+) neurons and GABAergic neurons. At the population level, odor discrimination was significantly better for RE(+) than CB(+) neurons, and was lowest for GABAergic neurons. Thus, we identified in LII of the LEC anatomically and functionally distinct neuronal subpopulations that engage differentially in feedforward and feedback signaling during odor processing

Untangling perceptual memory: hysteresis and adaptation map into separate cortical networks

Perception is an active inferential process in which prior knowledge is combined with sensory input, the result of which determines the contents of awareness. Accordingly, previous experience is known to help the brain "decide" what to perceive. However, a critical aspect that has not been addressed is that previous experience can exert 2 opposing effects on perception: An attractive effect, sensitizing the brain to perceive the same again (hysteresis), or a repulsive effect, making it more likely to perceive something else (adaptation). We used functional magnetic resonance imaging and modeling to elucidate how the brain entertains these 2 opposing processes, and what determines the direction of such experience-dependent perceptual effects. We found that although affecting our perception concurrently, hysteresis and adaptation map into distinct cortical networks: a widespread network of higher-order visual and fronto-parietal areas was involved in perceptual stabilization, while adaptation was confined to early visual areas. This areal and hierarchical segregation may explain how the brain maintains the balance between exploiting redundancies and staying sensitive to new information. We provide a Bayesian model that accounts for the coexistence of hysteresis and adaptation by separating their causes into 2 distinct terms: Hysteresis alters the prior, whereas adaptation changes the sensory evidence (the likelihood function)

Ultrasonic courtship vocalizations in wild house mice: spectrographic analyses

House mice emit ultrasonic vocalizations (USVs) during courtship, which are sexually dimorphic and function to attract mates. Spectrographic analyses of laboratory mice show that USVs are surprisingly complex and have features of song. In this study, we conducted the first spectral and temporal analyses of recordings from wild house mice (F1 from wild-caught Mus musculus musculus ). Inspection of the spectral shape of syllables shows that the USVs from wild mice can be classified by both frequency and duration, and the most apparent distinction is between low- versus high-frequency calls. High-frequency calls of wild mice seem to be emitted at a much higher frequency range than previously found in some laboratory mice. Interestingly, we found that 20% of males do not vocalize at all, though the reason for their behaviour is unclear. Future studies are needed to determine what kind of information is conveyed in these complex vocalizations, and why some males appear to be non-vocalizers

EOSC-Life Report on the work of the initial demonstrators

Leitner F, Carazo JM, Bischof J, et al. EOSC-Life Report on the work of the initial demonstrators.This deliverable 3.2 is a report on the demonstrator projects, the eight scientific and technical pilot projects that were selected to provide concrete scientific use-cases and guide and structure the work done in EOSC-Life to build an open digital and collaborative space for biological and medical research. We report in this deliverable the process of integration of the demonstrators within EOSC-Life, the achievement of the demonstrators who developed and made available to the scientific community several valuable resources (databases, workflows, web platform...), the actions undertaken within EOSC-Life to disseminate the demonstrator achievement and finally the results of the demonstrator survey to learn from the demonstrator experience and improve the integration of the new pilot project within EOSC-Life. </ol

Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex

The lateral entorhinal cortex (LEC) computes and transfers olfactory information from the olfactory bulb to the hippocampus. Here we established LEC connectivity to upstream and downstream brain regions to understand how the LEC processes olfactory information. We report that, in layer II (LII), reelin- and calbindin-positive (RE(+) and CB(+)) neurons constitute two major excitatory cell types that are electrophysiologically distinct and differentially connected. RE(+) neurons convey information to the hippocampus, while CB(+) neurons project to the olfactory cortex and the olfactory bulb. In vivo calcium imaging revealed that RE(+) neurons responded with higher selectivity to specific odors than CB(+) neurons and GABAergic neurons. At the population level, odor discrimination was significantly better for RE(+) than CB(+) neurons, and was lowest for GABAergic neurons. Thus, we identified in LII of the LEC anatomically and functionally distinct neuronal subpopulations that engage differentially in feedforward and feedback signaling during odor processing

EOSC-Life Report on the work of the Open Call Projects

This Deliverable 3.3 is a report on the Digital Life Sciences Open Call and two Internal Calls organised by EOSC-Life WP3. The organisation of these Calls followed the successful integration and support of 8 Demonstrator projects&nbsp;which provided the first concrete use cases in the initial phase of EOSC-Life. The three Calls overall supported 11 scientific user projects, selected to facilitate integration of concrete use-cases across Life Sciences domains into the European Open Science Cloud (EOSC)&nbsp;framework. Through the Calls, the practical goal was to facilitate co-creation of an open, digital collaborative space for life science research by developing FAIR&nbsp;tools, workflows, resources, infrastructures, and guidelines together with the EOSC-Life RIs experts and communities. We report in this Deliverable the following achievements: Organisation of the EOSC-Life Open and Internal Calls; Integrating and training the EOSC-Life WP3 Open Call&nbsp;and Internal Call&nbsp;project teams in EOSC-Life; Activities for connecting project teams with EOSC-Life and LS-RI communities and dissemination of projects outcomes to broader communities; Work done in the individual projects, their results, and impact of developed resources; Recommendations from the EOSC-Life WP3 project teams and the EOSC-Life community for future Open Calls. </ol