Humoral immunity at the brain borders in homeostasis and a scRNA-seq atlas of immune cells at the CNS borders

https://www.cnsbordercellatlas.org/

Adaptation via innovation in the animal kingdom

Over the course of evolution, the human race has achieved a number of remarkable innovations, that have enabled us to adapt to and benefit from the environment ever more effectively. The ongoing environmental threats and health disasters of our world have now made it crucial to understand the cognitive mechanisms behind innovative behaviours. In my talk, I will present two research projects with examples of innovation-based behavioural adaptation from the taxonomic kingdom of animals, serving as a comparative psychological model for mapping the evolution of innovation. The first project focuses on the challenge of overcoming physical disability. In this study, we investigated an injured kea (Nestor notabilis) that exhibits an efficient, intentional, and innovative tool-use behaviour to compensate his disability, showing evidence for innovation-based adaptation to a physical disability in a non-human species. The second project focuses on the evolution of fire use from a cognitive perspective. Fire has been one of the most dominant ecological forces in human evolution; however, it is still unknown what capabilities and environmental factors could have led to the emergence of fire use. In the core study of this project, we investigated a captive population of Japanese macaques (Macaca fuscata) that has been regularly exposed to campfires during the cold winter months for over 60 years. Our results suggest that macaques are able to take advantage of the positive effects of fire while avoiding the dangers of flames and hot ashes, and exhibit calm behaviour around the bonfire. In addition, I will present a research proposal targeting the foraging behaviour of predatory birds in parts of Australia frequently affected by bushfires. Anecdotal reports suggest that some birds use burning sticks to spread the flames, a behaviour that has not been scientifically observed and evaluated. In summary, the two projects explore innovative behaviours along three different species groups, three different habitats, and three different ecological drivers, providing insights into the cognitive and behavioural mechanisms of adaptation through innovation.

Network inference via process motifs for lagged correlation in linear stochastic processes

A major challenge for causal inference from time-series data is the trade-off between computational feasibility and accuracy. Motivated by process motifs for lagged covariance in an autoregressive model with slow mean-reversion, we propose to infer networks of causal relations via pairwise edge measure (PEMs) that one can easily compute from lagged correlation matrices. Motivated by contributions of process motifs to covariance and lagged variance, we formulate two PEMs that correct for confounding factors and for reverse causation. To demonstrate the performance of our PEMs, we consider network interference from simulations of linear stochastic processes, and we show that our proposed PEMs can infer networks accurately and efficiently. Specifically, for slightly autocorrelated time-series data, our approach achieves accuracies higher than or similar to Granger causality, transfer entropy, and convergent crossmapping -- but with much shorter computation time than possible with any of these methods. Our fast and accurate PEMs are easy-to-implement methods for network inference with a clear theoretical underpinning. They provide promising alternatives to current paradigms for the inference of linear models from time-series data, including Granger causality, vector-autoregression, and sparse inverse covariance estimation.

Tree of life: The cerebellum in anger and aggression

From single cell to population coding during defensive behaviors in prefrontal circuits

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. Over the past years, we used a combination we used a combination of extracellular recordings, neuronal decoding approaches, and state of the art optogenetic manipulations to identify key neuronal elements and mechanisms controlling defensive fear responses. I will present an overview of our recent work ranging from analyses of dedicated neuronal types and oscillatory and synchronization mechanisms to artificial intelligence approaches used to decode the activity or large population of neurons. Ultimately these analyses allowed the identification of high dimensional representations of defensive behavior unfolding within prefrontal networks.

Multimodal framework and fusion of EEG, graph theory and sentiment analysis for the prediction and interpretation of consumer decision

The application of neuroimaging methods to marketing has recently gained lots of attention. In analyzing consumer behaviors, the inclusion of neuroimaging tools and methods is improving our understanding of consumer’s preferences. Human emotions play a significant role in decision making and critical thinking. Emotion classification using EEG data and machine learning techniques has been on the rise in the recent past. We evaluate different feature extraction techniques, feature selection techniques and propose the optimal set of features and electrodes for emotion recognition.Affective neuroscience research can help in detecting emotions when a consumer responds to an advertisement. Successful emotional elicitation is a verification of the effectiveness of an advertisement. EEG provides a cost effective alternative to measure advertisement effectiveness while eliminating several drawbacks of the existing market research tools which depend on self-reporting. We used Graph theoretical principles to differentiate brain connectivity graphs when a consumer likes a logo versus a consumer disliking a logo. The fusion of EEG and sentiment analysis can be a real game changer and this combination has the power and potential to provide innovative tools for market research.

NMC4 Short Talk: Directly interfacing brain and deep networks exposes non-hierarchical visual processing

A recent approach to understanding the mammalian visual system is to show correspondence between the sequential stages of processing in the ventral stream with layers in a deep convolutional neural network (DCNN), providing evidence that visual information is processed hierarchically, with successive stages containing ever higher-level information. However, correspondence is usually defined as shared variance between brain region and model layer. We propose that task-relevant variance is a stricter test: If a DCNN layer corresponds to a brain region, then substituting the model’s activity with brain activity should successfully drive the model’s object recognition decision. Using this approach on three datasets (human fMRI and macaque neuron firing rates) we found that in contrast to the hierarchical view, all ventral stream regions corresponded best to later model layers. That is, all regions contain high-level information about object category. We hypothesised that this is due to recurrent connections propagating high-level visual information from later regions back to early regions, in contrast to the exclusively feed-forward connectivity of DCNNs. Using task-relevant correspondence with a late DCNN layer akin to a tracer, we used Granger causal modelling to show late-DCNN correspondence in IT drives correspondence in V4. Our analysis suggests, effectively, that no ventral stream region can be appropriately characterised as ‘early’ beyond 70ms after stimulus presentation, challenging hierarchical models. More broadly, we ask what it means for a model component and brain region to correspond: beyond quantifying shared variance, we must consider the functional role in the computation. We also demonstrate that using a DCNN to decode high-level conceptual information from ventral stream produces a general mapping from brain to model activation space, which generalises to novel classes held-out from training data. This suggests future possibilities for brain-machine interface with high-level conceptual information, beyond current designs that interface with the sensorimotor periphery.

Appearance-based impression formation

Despite the common advice “not to judge a book by its cover”, we form impressions of character within a second of seeing a stranger’s face. These impressions have widespread consequences for society and for the economy, making it vital that we have a clear theoretical understanding of which impressions are important and how they are formed. In my talk, I outline a data-driven approach to answering these questions, starting by building models of the key dimensions underlying impressions of naturalistic face images. Overall, my findings suggest deeper links between the fields of face perception and social stereotyping than have previously been recognised.

“From the Sublime to the Stomatopod: the story from beginning to nowhere near the end.”

“Call me a marine vision scientist. Some years ago - never mind how long precisely - having little or no money in my purse, and nothing particular to interest me on shore, I thought I would sail about a little and see what animals see in the watery part of the world. It is a way I have of dividing off the spectrum, and regulating circular polarisation.” Sometimes I wish I had just set out to harpoon a white whale as it would have been easier than studying stomatopod (mantis shrimp) vision. Nowhere near as much fun of course and certainly less dangerous so in this presentation I track the history of discovery and confusion that stomatopods deliver in trying to understand what the do actually see. The talk unashamedly borrows from that of Mike Bok a few weeks ago (April 13th 2021 “The Blurry Beginnings: etc” talk) as an introduction to the system (do go look at his talk again, it is beautiful!) and goes both backwards and forwards in time, trying to provide an explanation for the design of this visual system. The journey is again one of retinal anatomy and physiology, neuroanatomy, electrophysiology, behaviour and body ornaments but this time focusses more on polarisation vision (Mike covered the colour stuff well). There is a comparative section looking at the cephalopods too and by the end, I hope you will understand where we are at with trying to understand this extraordinary way of seeing the world and why we ‘pod-people’ wave our arms around so much when asked to explain; what do stomatopods see? Maybe, to butcher another quote: “mantis shrimp have been rendered visually beautiful for vision’s sake.”

Using extra-hippocampal cognitive maps for goal-directed spatial navigation

Goal-directed navigation requires precise estimates of spatial relationships between current position and future goal, as well as planning of an associated route or action. While neurons in the hippocampal formation can represent the animal’s position and nearby trajectories, their role in determining the animal’s destination or action has been questioned. We thus hypothesize that brain regions outside the hippocampal formation may play complementary roles in navigation, particularly for guiding goal-directed behaviours based on the brain’s internal cognitive map. In this seminar, I will first describe a subpopulation of neurons in the retrosplenial cortex (RSC) that increase their firing when the animal approaches environmental boundaries, such as walls or edges. This boundary coding is independent of direct visual or tactile sensation but instead depends on inputs from the medial entorhinal cortex (MEC) that contains spatial tuning cells, such as grid cells or border cells. However, unlike MEC border cells, we found that RSC border cells encode environmental boundaries in a self-centred egocentric coordinate frame, which may allow an animal for efficient avoidance from approaching walls or edges during navigation. I will then discuss whether the brain can possess a precise estimate of remote target location during active environmental exploration. Such a spatial code has not been described in the hippocampal formation. However, we found that neurons in the rat orbitofrontal cortex (OFC) form spatial representations that persistently point to the animal’s subsequent goal destination throughout navigation. This destination coding emerges before navigation onset without direct sensory access to a distal goal, and are maintained via destination-specific neural ensemble dynamics. These findings together suggest key roles for extra-hippocampal regions in spatial navigation, enabling animals to choose appropriate actions toward a desired destination by avoiding possible dangers.

Dynamical population coding during defensive behaviours in prefrontal circuits

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.

As soon as there was life there was danger

Organisms face challenges to survival throughout life. When we freeze or flee in danger, we often feel fear. Tracing the deep history of danger gives a different perspective. The first cells living billions of years ago had to detect and respond to danger in order to survive. Life is about not being dead, and behavior is a major way that organisms hold death off. Although behavior does not require a nervous system, complex organisms have brain circuits for detecting and responding to danger, the deep roots of which go back to the first cells. But these circuits do not make fear, and fear is not the cause of why we freeze or flee. Fear a human invention; a construct we use to account for what happens in our minds when we become aware that we are in harm’s way. This requires a brain that can personally know that it existed in the past, that it is the entity that might be harmed in the present, and that it will cease to exist it the future. If other animals have conscious experiences, they cannot have the kinds of conscious experiences we have because they do not have the kinds of brains we have. This is not meant as a denial of animal consciousness; it is simply a statement about the fact that every species has a different brain. Nor is it a declaration about the wonders of the human brain, since we have done some wonderful, but also horrific, things with our brains. In fact, we are on the way to a climatic disaster that will not, as some suggest, destroy the Earth. But it will make it inhabitable for our kind, and other organisms with high energy demands. Bacteria have made it for billions of years and will likely be fine. The rest is up for grabs, and, in a very real sense, up to us.

What to consider, when making strategic social decisions? An Eye-tracking investigation

In many societal problems, individuals exhibit a conflict between keeping resources (e.g., money, time or attention) to themselves or sharing them with another individual or group. The reasons motivating decisions in favor of others welfare can thereby vary from purely altruistic to completely strategic. Be it the stranger making an effort returning a lost valet to its rightful owner or a co-worker pitching in her fair share in a joint project. Actions like that create an environment that makes living together a pleasant experience. Hence, understanding how decisions determining the welfare of oneself and others are made is important for facilitating this behavior by building institutions that maximize the rate of cooperation in a society. To shed new light on such decision making processes I will present recent evidence from a set of process tracing experiments utilizing eye-tracking and economic games. Experiments will focus on the role of social preferences in the choice construction process and will identify mechanisms (i.e., search and processing depth, information weighting, and ignorance) through which they guide choice behavior. I will in particular focus on the differences and commonalitiesbetween strategic and altruistic decisions. Specifically, investigating to which extent people direct attention towards certain components of the decision situation in a context-dependent manner.

Untitled Seminar

Blurring the boundaries between neuroscience and organismal physiology

Work in my laboratory is based on the assumptions that we do not know yet how all physiological functions are regulated and that mouse genetics by allowing to identify novel inter-organ communications is the most efficient ways to identify novel regulation of physiological functions. We test these two contention through the study of bone which is the organ my lab has studied since its inception. Based on precise cell biological and clinical reasons that will be presented during the seminar we hypothesized that bone should be a regulator of energy metabolism and reproduction and identified a bone-derived hormone termed osteocalcin that is responsible of these regulatory events. The study of this hormone revealed that in addition to its predicted functions it also regulates brain size, hippocampus development, prevents anxiety and depression and favors spatial learning and memory by signaling through a specific receptor we characterized. As will be presented, we elucidated some of the molecular events accounting for the influence of osteocalcin on brain and showed that maternal osteocalcin is the pool of this hormone that affects brain development. Subsequently and looking at all the physiological functions regulated by osteocalcin, i.e., memory, the ability to exercise, glucose metabolism, the regulation of testosterone biosynthesis, we realized that are all need or regulated in the case of danger. In other words it suggested that osteocalcin is an hormone needed to sense and overcome acute danger. Consonant with this hypothesis we next showed this led us to demonstrate that bone via osteocalcin is needed to mount an acute stress response through molecular and cellular mechanisms that will be presented during the seminar. overall, an evolutionary appraisal of bone biology, this body of work and experiments ongoing in the lab concur to suggest 1] the appearance of bone during evolution has changed how physiological functions as diverse as memory, the acute stress response but also exercise and glucose metabolism are regulated and 2] identified bone and osteocalcin as its molecular vector, as an organ needed to sense and response to danger.

Dynamical population coding during defensive behaviours in prefrontal circuits

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.

Differential contribution of distinct neuronal populations to danger representations

FENS Forum 2024

Dorsal raphe nuclei/ventrolateral periaqueductal grey and cerebellar fastigial nucleus interactions modulate danger response during fear learning

FENS Forum 2024

Localization and function of the Na+/H+ exchanger NHE6 (SLC9A6) in primary neurons

FENS Forum 2024

Maternal versus stranger’s touch at 10 months: An fNIRS study

FENS Forum 2024

Novel biomarker of seizure onset zone based on Granger causality

FENS Forum 2024

Role of Na+/Ca2+ exchanger NCX in glioblastoma cell migration

FENS Forum 2024