Personalized medicine and predictive health and wellness: Adding the chemical component

Wearable sensors that detect and quantify biomarkers in retrievable biofluids (e.g., interstitial fluid, sweat, tears) provide information on human dynamic physiological and psychological states. This information can transform health and wellness by providing actionable feedback. Due to outdated and insufficiently sensitive technologies, current on-body sensing systems have capabilities limited to pH, and a few high-concentration electrolytes, metabolites, and nutrients. As such, wearable sensing systems cannot detect key low-concentration biomarkers indicative of stress, inflammation, metabolic, and reproductive status.  We are revolutionizing sensing. Our electronic biosensors detect virtually any signaling molecule or metabolite at ultra-low levels. We have monitored serotonin, dopamine, cortisol, phenylalanine, estradiol, progesterone, and glucose in blood, sweat, interstitial fluid, and tears. The sensors are based on modern nanoscale semiconductor transistors that are straightforwardly scalable for manufacturing. We are developing sensors for >40 biomarkers for personalized continuous monitoring (e.g., smartwatch, wearable patch) that will provide feedback for treating chronic health conditions (e.g., perimenopause, stress disorders, phenylketonuria). Moreover, our sensors will enable female fertility monitoring and the adoption of more healthy lifestyles to prevent disease and improve physical and cognitive performance.

Open source FPGA tools for building research devices

Edmund will present why to use FPGAs when building scientific instruments, when and why to use open source FPGA tools, the history of their development, their development status, currently supported FPGA families and functions, current developments in design languages and tools, the community, freely available design blocks, and possible future developments.

BrainLM Journal Club

Connor Lane will lead a journal club on the recent BrainLM preprint, a foundation model for fMRI trained using self-supervised masked autoencoder training. Preprint: https://www.biorxiv.org/content/10.1101/2023.09.12.557460v1 Tweeprint: https://twitter.com/david_van_dijk/status/1702336882301112631?t=Q2-U92-BpJUBh9C35iUbUA&s=19

Social and non-social learning: Common, or specialised, mechanisms? (BACN Early Career Prize Lecture 2022)

The last decade has seen a burgeoning interest in studying the neural and computational mechanisms that underpin social learning (learning from others). Many findings support the view that learning from other people is underpinned by the same, ‘domain-general’, mechanisms underpinning learning from non-social stimuli. Despite this, the idea that humans possess social-specific learning mechanisms - adaptive specializations moulded by natural selection to cope with the pressures of group living - persists. In this talk I explore the persistence of this idea. First, I present dissociations between social and non-social learning - patterns of data which are difficult to explain under the domain-general thesis and which therefore support the idea that we have evolved special mechanisms for social learning. Subsequently, I argue that most studies that have dissociated social and non-social learning have employed paradigms in which social information comprises a secondary, additional, source of information that can be used to supplement learning from non-social stimuli. Thus, in most extant paradigms, social and non-social learning differ both in terms of social nature (social or non-social) and status (primary or secondary). I conclude that status is an important driver of apparent differences between social and non-social learning. When we account for differences in status, we see that social and non-social learning share common (dopamine-mediated) mechanisms.

What shapes the transcriptional identity of a neuron?

Within the vertebrate neocortex and other telencephalic structures, molecularly-defined neurons tend to segregate at first order into GABAergic types and glutamatergic types. Two fundamental questions arise: (1) do non-telencephalic neurons similarly segregate by neurotransmitter status, and (2) do GABAergic (or glutamatergic) types sampled in different structures share many molecular features in common, beyond the few genes directly responsible for neurotransmitter synthesis and release? To address these questions, we used single-nucleus RNA sequencing, analyzing over 2.4 million brain cells sampled from 16 locations in a primate (the common marmoset). Unexpectedly, we find the answer to both is “no”. I will discuss implications for generalizing associations between neurotransmitter utilization and other phenotypes, and share ongoing efforts to map the biodistributions of cell types in the primate brain.

Redox and mitochondrial dysregulation in epilepsy

Epileptic seizures render the brain uniquely dependent on energy producing pathways. Studies in our laboratory have been focused on the role of redox processes and mitochondria in the context of abnormal neuronal excitability associated with epilepsy. We have shown that that status epilepticus (SE) alters mitochondrial and cellular redox status, energetics and function and conversely, that reactive oxygen species and resultant dysfunction can lead to chronic epilepsy. Oxidative stress and neuroinflammatory pathways have considerable crosstalk and targeting redox processes has recently been shown to control neuroinflammation and excitability. Understanding the role of metabolic and redox processes can enable the development of novel therapeutics to control epilepsy and/or its comorbidities.

Neuroscience of socioeconomic status and poverty: Is it actionable?

SES neuroscience, using imaging and other methods, has revealed generalizations of interest for population neuroscience and the study of individual differences. But beyond its scientific interest, SES is a topic of societal importance. Does neuroscience offer any useful insights for promoting socioeconomic justice and reducing the harms of poverty? In this talk I will use research from my own lab and others’ to argue that SES neuroscience has the potential to contribute to policy in this area, although its application is premature at present. I will also attempt to forecast the ways in which practical solutions to the problems of poverty may emerge from SES neuroscience. Bio: Martha Farah has conducted groundbreaking research on face and object recognition, visual attention, mental imagery, and semantic memory and - in more recent times - has been at the forefront of interdisciplinary research into neuroscience and society. This deals with topics such as using fMRI for lie detection, ethics of cognitive enhancement, and effects of social deprivation on brain development.

What is Cognitive Neuropsychology Good For? An Unauthorized Biography

Abstract: There is no doubt that the study of brain damaged individuals has contributed greatly to our understanding of the mind/brain. Within this broad approach, cognitive neuropsychology accentuates the cognitive dimension: it investigates the structure and organization of perceptual, motor, cognitive, and language systems – prerequisites for understanding the functional organization of the brain – through the analysis of their dysfunction following brain damage. Significant insights have come specifically from this paradigm. But progress has been slow and enthusiasm for this approach has waned somewhat in recent years, and the use of existing findings to constrain new theories has also waned. What explains the current diminished status of cognitive neuropsychology? One reason may be failure to calibrate expectations about the effective contribution of different subfields of the study of the mind/brain as these are determined by their natural peculiarities – such factors as the types of available observations and their complexity, opportunity of access to such observations, the possibility of controlled experimentation, and the like. Here, I also explore the merits and limitations of cognitive neuropsychology, with particular focus on the role of intellectual, pragmatic, and societal factors that determine scientific practice within the broader domains of cognitive science/neuroscience. I conclude on an optimistic note about the continuing unique importance of cognitive neuropsychology: although limited to the study of experiments of nature, it offers a privileged window into significant aspects of the mind/brain that are not easily accessible through other approaches. Biography: Alfonso Caramazza's research has focussed extensively on how words and their meanings are represented in the brain. His early pioneering studies helped to reformulate our thinking about Broca's aphasia (not limited to production) and formalised the logic of patient-based neuropsychology. More recently he has been instrumental in reconsidering popular claims about embodied cognition.

Interpersonal synchrony of body/brain, Solo & Team Flow

Flow is defined as an altered state of consciousness with excessive attention and enormous sense of pleasure, when engaged in a challenging task, first postulated by a psychologist, the late M. Csikszentmihayli. The main focus of this talk will be “Team Flow,” but there were two lines of previous studies in our laboratory as its background. First is inter-body and inter-brain coordination/synchrony between individuals. Considering various rhythmic echoing/synchronization phenomena in animal behavior, it could be regarded as the biological, sub-symbolic and implicit origin of social interactions. The second line of precursor research is on the state of Solo Flow in game playing. We employed attenuation of AEP (Auditory Evoked Potential) to task-irrelevant sound probes as an objective-neural indicator of such a Flow status, and found that; 1) Mutual link between the ACC & the TP is critical, and 2) overall, top-down influence is enhanced while bottom-up causality is attenuated. Having these as the background, I will present our latest study of Team Flow in game playing. We found that; 3) the neural correlates of Team Flow is distinctively different from those of Solo Flow nor of non-flow social, 4) the left medial temporal cortex seems to form an integrative node for Team Flow, receiving input related to Solo Flow state from the right PFC and input related to social state from the right IFC, and 5) Intra-brain (dis)similarity of brain activity well predicts (dis)similarity of skills/cognition as well as affinity for inter-brain coherence.

Mechanisms of sleep-seizure interactions in tuberous sclerosis and other mTORpathies

An intriguing, relatively unexplored therapeutic avenue to investigate epilepsy is the interaction of sleep mechanisms and seizures. Multiple lines of clinical observations suggest a strong, bi-directional relationship between epilepsy and sleep. Epilepsy and sleep disorders are common comorbidities. Seizures occur more commonly in sleep in many types of epilepsy, and in turn, seizures can cause disrupted sleep. Sudden unexplained death in epilepsy (SUDEP) is strongly associated with sleep. The biological mechanisms underlying this relationship between seizures and sleep are poorly understood, but if better delineated, could offer novel therapeutic approaches to treating both epilepsy and sleep disorders. In this presentation, I will explore this sleep-seizure relationship in mouse models of epilepsy. First, I will present general approaches for performing detailed longitudinal sleep and vigilance state analysis in mice, including pre-weanling neonatal mice. I will then discuss recent data from my laboratory demonstrating an abnormal sleep phenotype in a mouse model of the genetic epilepsy, tuberous sclerosis complex (TSC), and its relationship to seizures. The potential mechanistic basis of sleep abnormalities and sleep-seizure interactions in this TSC model will be investigated, focusing on the role of the mechanistic target of rapamycin (mTOR) pathway and hypothalamic orexin, with potential therapeutic applications of mTOR inhibitors and orexin antagonists. Finally, similar sleep-seizure interactions and mechanisms will be extended to models of acquired epilepsy due to status epilepticus-related brain injury.

JAK/STAT regulation of the transcriptomic response during epileptogenesis

Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and neural circuit remodeling in the hippocampus resulting in increased susceptibility to spontaneous seizures and cognitive dysfunction. Targeting these cascades could prevent or reverse symptom progression and has the potential to provide viable disease-modifying treatments that could reduce the portion of TLE patients (>30%) not responsive to current medical therapies. Changes in GABA(A) receptor subunit expression have been implicated in the pathogenesis of TLE, and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has been shown to be a key regulator of these changes. The JAK/STAT pathway is known to be involved in inflammation and immunity, and to be critical for neuronal functions such as synaptic plasticity and synaptogenesis. Our laboratories have shown that a STAT3 inhibitor, WP1066, could greatly reduce the number of spontaneous recurrent seizures (SRS) in an animal model of pilocarpine-induced status epilepticus (SE). This suggests promise for JAK/STAT inhibitors as disease-modifying therapies, however, the potential adverse effects of systemic or global CNS pathway inhibition limits their use. Development of more targeted therapeutics will require a detailed understanding of JAK/STAT-induced epileptogenic responses in different cell types. To this end, we have developed a new transgenic line where dimer-dependent STAT3 signaling is functionally knocked out (fKO) by tamoxifen-induced Cre expression specifically in forebrain excitatory neurons (eNs) via the Calcium/Calmodulin Dependent Protein Kinase II alpha (CamK2a) promoter. Most recently, we have demonstrated that STAT3 KO in excitatory neurons (eNSTAT3fKO) markedly reduces the progression of epilepsy (SRS frequency) in the intrahippocampal kainate (IHKA) TLE model and protects mice from kainic acid (KA)-induced memory deficits as assessed by Contextual Fear Conditioning. Using data from bulk hippocampal tissue RNA-sequencing, we further discovered a transcriptomic signature for the IHKA model that contains a substantial number of genes, particularly in synaptic plasticity and inflammatory gene networks, that are down-regulated after KA-induced SE in wild-type but not eNSTAT3fKO mice. Finally, we will review data from other models of brain injury that lead to epilepsy, such as TBI, that implicate activation of the JAK/STAT pathway that may contribute to epilepsy development.

Why Some Intelligent Agents are Conscious

In this talk I will present an account of how an agent designed or evolved to be intelligent may come to enjoy subjective experiences. First, the agent is stipulated to be capable of (meta)representing subjective ‘qualitative’ sensory information, in the sense that it can easily assess how exactly similar a sensory signal is to all other possible sensory signals. This information is subjective in the sense that it concerns how the different stimuli can be distinguished by the agent itself, rather than how physically similar they are. For this to happen, sensory coding needs to satisfy sparsity and smoothness constraints, which are known to facilitate metacognition and generalization. Second, this qualitative information can under some specific circumstances acquire an ‘assertoric force’. This happens when a certain self-monitoring mechanism decides that the qualitative information reliably tracks the current state of the world, and informs a general symbolic reasoning system of this fact. I will argue that the having of subjective conscious experiences amounts to nothing more than having qualitative sensory information acquiring an assertoric status within one’s belief system. When this happens, the perceptual content presents itself as reflecting the state of the world right now, in ways that seem undeniably rational to the agent. At the same time, without effort, the agent also knows what the perceptual content is like, in terms of how subjectively similar it is to all other possible precepts. I will discuss the computational benefits of this architecture, for which consciousness might have arisen as a byproduct.

Neural mechanisms of altered states of consciousness under psychedelics

Interest in psychedelic compounds is growing due to their remarkable potential for understanding altered neural states and their breakthrough status to treat various psychiatric disorders. However, there are major knowledge gaps regarding how psychedelics affect the brain. The Computational Neuroscience Laboratory at the Turner Institute for Brain and Mental Health, Monash University, uses multimodal neuroimaging to test hypotheses of the brain’s functional reorganisation under psychedelics, informed by the accounts of hierarchical predictive processing, using dynamic causal modelling (DCM). DCM is a generative modelling technique which allows to infer the directed connectivity among brain regions using functional brain imaging measurements. In this webinar, Associate Professor Adeel Razi and PhD candidate Devon Stoliker will showcase a series of previous and new findings of how changes to synaptic mechanisms, under the control of serotonin receptors, across the brain hierarchy influence sensory and associative brain connectivity. Understanding these neural mechanisms of subjective and therapeutic effects of psychedelics is critical for rational development of novel treatments and for the design and success of future clinical trials. Associate Professor Adeel Razi is a NHMRC Investigator Fellow and CIFAR Azrieli Global Scholar at the Turner Institute of Brain and Mental Health, Monash University. He performs cross-disciplinary research combining engineering, physics, and machine-learning. Devon Stoliker is a PhD candidate at the Turner Institute for Brain and Mental Health, Monash University. His interest in consciousness and psychiatry has led him to investigate the neural mechanisms of classic psychedelic effects in the brain.

Learning to see Stuff

Materials with complex appearances, like textiles and foodstuffs, pose challenges for conventional theories of vision. How does the brain learn to see properties of the world—like the glossiness of a surface—that cannot be measured by any other senses? Recent advances in unsupervised deep learning may help shed light on material perception. I will show how an unsupervised deep neural network trained on an artificial environment of surfaces that have different shapes, materials and lighting, spontaneously comes to encode those factors in its internal representations. Most strikingly, the model makes patterns of errors in its perception of material that follow, on an image-by-image basis, the patterns of errors made by human observers. Unsupervised deep learning may provide a coherent framework for how many perceptual dimensions form, in material perception and beyond.

Evidence for the role of glymphatic dysfunction in the development of Alzheimer’s disease

Glymphatic perivascular exchange is supported by the astroglial water channel aquaporin-4 (AQP4), which localizes to perivascular astrocytic endfeet surrounding the cerebral vasculature. In aging mice, impairment of glymphatic function is associated with reduced perivascular AQP4 localization, yet whether these changes contribute to the development of neurodegenerative disease, such as Alzheimer’s disease (AD), remains unknown. Using post mortem human tissue, we evaluated perivascular AQP4 localization in the frontal cortical gray matter, white matter, and hippocampus of cognitively normal subjects and those with AD. Loss of perivascular and increasing cellular localization of AQP4 in the frontal gray matter was specifically associated with AD status, amyloid β (Aβ) and tau pathology, and cognitive decline in the early stages of disease. Using AAV-PHP.B to drive expression on non-perivascular AQP4 in wild type and Tg2576 (APPSwe, mouse model of Aβ deposition) mice, increased cellular AQP4 localization did not slow glymphatic function or change Aβ deposition. Using the Snta1 knockout line (which lacks perivascular AQP4 localization), we observed that loss AQP4 from perivascular endfeet slowed glymphatic function in wild type mice and accelerated Aβ plaque deposition in Tg2576 mice. These findings demonstrate that loss of perivascular AQP4 localization, and not increased cellular AQP4 localization, slows glymphatic function and promotes the development of AD pathology. To evaluate whether naturally occurring variation in the human AQP4 gene, or the alpha syntrophin (SNTA1), dystrobrevin (DTNA) or dystroglycan (DAG1) genes (whose products maintain perivascular AQP4 localization) confer risk for or protection from AD pathology or clinical progression, we evaluated 56 tag single nucleotide polymorphisms (SNPs) across these genes for association with CSF AD biomarkers, MRI measures of cortical and hippocampal atrophy, and longitudinal cognitive decline in the Alzheimer’s Disease Neuroimaging Initiative I (ADNI I) cohort. We identify 25 different significant associations between AQP4, SNTA1, DTNA, and DAG1 tag SNPs and phenotypic measures of AD pathology and progression. These findings provide complimentary human genetic evidence for the contribution of perivascular glymphatic dysfunction to the development of AD in human populations.

Dancing to a Different Tune: TANGO Gives Hope for Dravet Syndrome

The long-term goal of our research is to understand the mechanisms of SUDEP, defined as Sudden, Unexpected, witnessed or unwitnessed, nontraumatic and non-drowning Death in patients with EPilepsy, excluding cases of documented status epilepticus. The majority of SUDEP patients die during sleep. SUDEP is the most devastating consequence of epilepsy, yet little is understood about its causes and no biomarkers exist to identify at risk patients. While SUDEP accounts for 7.5-20% of all epilepsy deaths, SUDEP risk in the genetic epilepsies varies with affected genes. Patients with ion channel gene variants have the highest SUDEP risk. Indirect evidence variably links SUDEP to seizure-induced apnea, pulmonary edema, dysregulation of cerebral circulation, autonomic dysfunction, and cardiac arrhythmias. Arrhythmias may be primary or secondary to hormonal or metabolic changes, or autonomic discharges. When SUDEP is compared to Sudden Cardiac Death secondary to Long QT Syndrome, especially to LQT3 linked to variants in the voltage-gated sodium channel (VGSC) gene SCN5A, there are parallels in the circumstances of death. To gain insight into SUDEP mechanisms, our approach has focused on channelopathies with high SUDEP incidence. One such disorder is Dravet syndrome (DS), a devastating form of developmental and epileptic encephalopathy (DEE) characterized by multiple pharmacoresistant seizure types, intellectual disability, ataxia, and increased mortality. While all patients with epilepsy are at risk for SUDEP, DS patients may have the highest risk, up to 20%, with a mean age at SUDEP of 4.6 years. Over 80% of DS is caused by de novo heterozygous loss-of-function (LOF) variants in SCN1A, encoding the VGSC Nav1.1  subunit, resulting in haploinsufficiency. A smaller cohort of patients with DS or a more severe DEE have inherited, homozygous LOF variants in SCN1B, encoding the VGSC 1/1B non-pore-forming subunits. A related DEE, Early Infantile EE (EIEE) type 13, is linked to de novo heterozygous gain-of-function variants in SCN8A, encoding the VGSC Nav1.6. VGSCs underlie the rising phase and propagation of action potentials in neurons and cardiac myocytes. SCN1A, SCN8A, and SCN1B are expressed in both the heart and brain of humans and mice. Because of this, we proposed that cardiac arrhythmias contribute to the mechanism of SUDEP in DEE. We have taken a novel approach to the development of therapeutics for DS in collaboration with Stoke Therapeutics. We employed Targeted Augmentation of Nuclear Gene Output (TANGO) technology, which modulates naturally occurring, non-productive splicing events to increase target gene and protein expression and ameliorate disease phenotype in a mouse model. We identified antisense oligonucleotides (ASOs) that specifically increase the expression of productive Scn1a transcript in human and mouse cell lines, as well as in mouse brain. We showed that a single intracerebroventricular dose of a lead ASO at postnatal day 2 or 14 reduced the incidence of electrographic seizures and SUDEP in the F1:129S-Scn1a+/- x C57BL/6J mouse model of DS. Increased expression of productive Scn1a transcript and NaV1.1 protein were confirmed in brains of treated mice. Our results suggest that TANGO may provide a unique, gene-specific approach for the treatment of DS.

What are the consequences of directing attention within working memory?

The role of attention in working memory remains controversial, but there is some agreement on the notion that the focus of attention holds mnemonic representations in a privileged state of heightened accessibility in working memory, resulting in better memory performance for items that receive focused attention during retention. Closely related, representations held in the focus of attention are often observed to be robust and protected from degradation caused by either perceptual interference (e.g., Makovski & Jiang, 2007; van Moorselaar et al., 2015) or decay (e.g., Barrouillet et al., 2007). Recent findings indicate, however, that representations held in the focus of attention are particularly vulnerable to degradation, and thus, appear to be particularly fragile rather than robust (e.g., Hitch et al., 2018; Hu et al., 2014). The present set of experiments aims at understanding the apparent paradox of information in the focus of attention having a protected vs. vulnerable status in working memory. To that end, we examined the effect of perceptual interference on memory performance for information that was held within vs. outside the focus of attention, across different ways of bringing items in the focus of attention and across different time scales.

Autopilot v0.4.0 - Distributing development of a distributed experimental framework

Autopilot is a Python framework for performing complex behavioral neuroscience experiments by coordinating a swarm of Raspberry Pis. It was designed to not only give researchers a tool that allows them to perform the hardware-intensive experiments necessary for the next generation of naturalistic neuroscientific observation, but also to make it easier for scientists to be good stewards of the human knowledge project. Specifically, we designed Autopilot as a framework that lets its users contribute their technical expertise to a cumulative library of hardware interfaces and experimental designs, and produce data that is clean at the time of acquisition to lower barriers to open scientific practices. As autopilot matures, we have been progressively making these aspirations a reality. Currently we are preparing the release of Autopilot v0.4.0, which will include a new plugin system and wiki that makes use of semantic web technology to make a technical and contextual knowledge repository. By combining human readable text and semantic annotations in a wiki that makes contribution as easy as possible, we intend to make a communal knowledge system that gives a mechanism for sharing the contextual technical knowledge that is always excluded from methods sections, but is nonetheless necessary to perform cutting-edge experiments. By integrating it with Autopilot, we hope to make a first of its kind system that allows researchers to fluidly blend technical knowledge and open source hardware designs with the software necessary to use them. Reciprocally, we also hope that this system will support a kind of deep provenance that makes abstract "custom apparatus" statements in methods sections obsolete, allowing the scientific community to losslessly and effortlessly trace a dataset back to the code and hardware designs needed to replicate it. I will describe the basic architecture of Autopilot, recent work on its community contribution ecosystem, and the vision for the future of its development.

Multisensory encoding of self-motion in the retrosplenial cortex and beyond

In order to successfully navigate through the environment, animals must accurately estimate the status of their motion with respect to the surrounding scene and objects. In this talk, I will present our recent work on how retrosplenial cortical (RSC) neurons combine vestibular and visual signals to reliably encode the direction and speed of head turns during passive motion and active navigation. I will discuss these data in the context of RSC long-range connectivity and further show our ongoing work on building population-level models of motion representation across cortical and subcortical networks.

Molecular, receptor, and neural bases for chemosensory-mediated sexual and social behavior in mice

For many animals, the sense of olfaction plays a major role in controlling sexual behaviors. Olfaction helps animals to detect mates, discriminate their status, and ultimately, decide on their behavioral output such as courtship behavior or aggression. Specific pheromone cues and receptors have provided a useful model to study how sensory inputs are converted into certain behavioral outputs. With the aid of recent advances in tools to record and manipulate genetically defined neurons, our understanding of the neural basis of sexual and social behavior has expanded substantially. I will discuss the current understanding of the neural processing of sex pheromones and the neural circuitry which controls sexual and social behaviors and ultimately reproduction, by focusing on rodent studies, mainly in mice, and the vomeronasal sensory system.

Contrasting neuronal circuits driving reactive and cognitive fear

The last decade in the field of neuroscience has been marked by intense debate on the meaning of the term fear. Whereas some have argued that fear (as well as other emotions) relies on cognitive capacities that are unique to humans, others view it as a negative state constructed from essential building blocks. This latter definition posits that fear states are associated with varying readouts that one could consider to be parallel processes or serial events tied to a specific hierarchy. Within this framework, innate defensive behaviors are considered to be common displays of fear states that lie under the control of hard-wired brain circuits. As a general rule, these defensive behaviors can be classified as either reactive or cognitive based on a thread imminence continuum. However, while evidence of the neuronal circuits that lead to these divergent behavioral strategies has accrued over the last decades, most literature has considered these responses in isolation. As a result, important misconceptions have arisen regarding how fear circuits are distributed in the brain and the contribution of specific nodes within these circuits to defensive behaviors. To mitigate the status quo, I will conduct a systematic comparison of brain circuits driving the expression of freezing and active avoidance behavior, which I will use as well-studied proxies of reactive and cognitive fear, respectively. In addition, I propose that by integrating associative information with interoceptive and exteroceptive signals the central nucleus of the amygdala plays a crucial role in biasing the selection of defensive behaviors.

Inclusive Basic Research

Methodology for understanding the basic phenomena of life can be done in vitro or in vivo, under tightly-controlled experimental conditions designed to limit variability. However stringent the protocol, these experiments do not occur in a cultural vacuum and they are often subject to the same societal biases as other research disciplines. Many researchers uphold the status quo of biased basic research by not questioning the characteristics of their experimental animals, or the people from whom their tissue samples were collected. This means that our fundamental understanding of life has been built on biased models. This session will explore the ways in which basic life sciences research can be biased and the implications of this. We will discuss practical ways to assess your research design and how to make sure it is representative.

The Evolution of Looking and Seeing: New Insights from Colorful Jumping Spiders

During communication, alignment between signals and sensors can be critical. Signals are often best perceived from specific angles, and sensory systems can also exhibit strong directional biases. However, we know little about how animals establish and maintain such signaling alignment during communication. To investigate this, we characterized the spatial dynamics of visual courtship signal- ing in the jumping spider Habronattus pyrrithrix. The male performs forward-facing displays involving complex color and movement patterns, with distinct long- and short-range phases. The female views displays with 2 distinct eye types and can only perceive colors and fine patterns of male displays when they are presented in her frontal field of view. Whether and how courtship interactions pro- duce such alignment between male display and female field of view is unknown. We recorded relative positions and orientations of both actors throughout courtship and established the role of each sex in maintaining signaling alignment. Males always oriented their displays toward the female. However, when females were free to move, male displays were consistently aligned with female princi- pal eyes only during short-range courtship. When female position was fixed, signaling alignment consistently occurred during both phases, suggesting that female movement reduces communication efficacy. When female models were experimentally rotated to face away during courtship, males rarely repositioned themselves to re-align their display. However, males were more likely to present cer- tain display elements after females turned to face them. Thus, although signaling alignment is a function of both sexes, males appear to rely on female behavior for effective communication

Sparse expansion in cerebellum favours learning speed and performance in the context of motor control

The cerebellum contains more than half of the brain’s neurons and it is essential for motor control. Its neural circuits have a distinctive architecture comprised of a large, sparse expansion from the input mossy fibres to the granule cell layer. For years, theories of how cerebellar architectural features relate to cerebellar function have been formulated. It has been shown that some of these features can facilitate pattern separation. However, these theories don’t consider the need for it to learn fast in order to control smooth and accurate movements. Here, we confront this gap. This talk will show that the expansion to the granule cell layer in the cerebellar cortex improves learning speed and performance in the context of motor control by considering a cerebellar-like network learning an internal model of a motor apparatus online. By expressing the general form of the learning rate for such a system, this talk will provide a calculation of how increasing the number of granule cells diminishes the effect of noise and increases the learning speed. The researchers propose that the particular architecture of cerebellar circuits modifies the geometry of the error function in a favourable way for learning faster. Their results illuminate a new link between cerebellar structure and function.

The problem of power in single-case neuropsychology

Case-control comparisons are a gold standard method for diagnosing and researching neuropsychological deficits and dissociations at the single-case level. These statistical tests, developed by John Crawford and collaborators, provide quantitative criteria for the classical concepts of deficit, dissociation and double-dissociation. Much attention has been given to the control of Type I (false positive) errors for these tests, but far less to the avoidance of Type II (false negative) errors; that is, to statistical power. I will describe the origins and limits of statistical power for case-control comparisons, showing that there are hard upper limits on power, which have important implications for the design and interpretation of single-case studies. My aim is to stimulate discussion of the inferential status of single-case neuropsychological evidence, particularly with respect to contemporary ideals of open science and study preregistration.

The evolutionary and psychological origins of reciprocal cooperation

If only those behaviours evolve that increase the actor’s own survival and reproductive success, then it might come as a surprise that cooperative behaviours, i.e. providing benefits to others, are a widespread phenomenon. Many animals cooperate even with unrelated individuals in various contexts, like providing care or food. One possibility to explain these behaviours is reciprocity. Reciprocal cooperation, i.e. helping those that were helpful before, is a ubiquitous and important trait of human sociality. Still, the evolutionary origin of it is largely unclear, mainly because it is believed that other animals do not exchange help reciprocally. Consequently, reciprocity is suggested to have evolved in the human lineage only. In contrast to this, I propose that reciprocity is not necessarily cognitively demanding and likely to be widespread. In my talk, I will first shed light on the mechanisms of reciprocal cooperation in Norway rats (Rattus norvegicus). In a series of studies, my colleagues and I have demonstrated that Norway rats reciprocally exchange goods and services between and within different commodities and independent of kinship. Furthermore, to understand the evolutionary origins of human reciprocity, and whether it is shared with other animals, I will then discuss evidence for reciprocity in non-human primates, which are our closest living relatives. A thorough analysis of the findings showed that reciprocity is present and, for example, not confined to unrelated individuals, but that the choice of commodities can impact the likelihood of reciprocation. Based on my findings, I conclude that reciprocal cooperation in non-human animals is present but largely neglected and not restricted to humans. In order to deepen our understanding of the evolutionary origins of reciprocity in more general, future studies should investigate when and how reciprocity in non-human animals emerged and how it is maintained.

HCN2: a key ion channel driving pain, migraine and tinnitus

Gene Therapy for Neurodegeneration

One of the major challenges in developing therapeutics for the neurodegenerative disorders is the blood-brain barrier, limiting the availability of systemically administered therapies such as recombinant proteins or monoclonal antibodies from reaching the brain. Direct central nervous system (CNS) gene therapy using adeno-associated virus vectors expressing a therapeutic protein, monoclonal antibody or inhibiting RNA-coding sequences has two characteristics ideal for therapy of neurodegenerative disorders: circumventing the blood-brain barrier by directly expressing the therapy in the brain and the ability to provide persistent therapy with only a single administration. There are several critical parameters relevant to successful CNS gene therapy, including choice of vector, design of the gene to be expressed, delivery/route of administration, dose and anti-vector immune responses. The presentation will focus on these issues, the current status of clinical trials of gene therapy for neurodegeneration and specific challenges that will need to be overcome to ensure the success of these therapies.

Neuroendocrine control of female germline stem cell increase in the fruit fly Drosophila melanogaster

The development and maintenance of many tissues are fueled by stem cells. Many studies have addressed how intrinsic factors and local signals from neighboring niche cells maintain stem cell identity and proliferative potential. In contrast, it is poorly understood how stem cell activity is controlled by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Our laboratory has been focusing on female germline stem cells (fGSCs) in the fruit fly Drosophila melanogaster as a model system and studying neuroendocrine control of fGSC increase. The increase of fGSCs is induced by mating stimuli. We have previously reported that mating-induced fGSC increase is regulated by the ovarian steroid hormone and the enteroendocrine peptide hormone [Ameku & Niwa, PLOS Genetics 2016; Ameku et al. PLOS Biology 2018]. In this presentation, we report our recent finding showing a neuronal mechanism of mating-induced fGSC increase. We first found that the ovarian somatic cell-specific RNAi for Oamb, a G protein-coupled receptor for the neurotransmitter octopamine, failed to induce fGSC proliferation after mating. Both ex vivo and in vivo experiments revealed that octopamine and Oamb positively regulated mating-induced fGSC increase via intracellular Ca 2+ signaling. We also found that a small subset of octopaminergic neurons directly projected to the ovary, and neuronal activity of these neurons was required for mating-induced fGSC increase. This study provides a mechanism describing how the neuronal system controls stem cell behavior through stem cell niche signaling [Yoshinari et al. eLife 2020]. Here I will also present our recent data showing how the neuroendocrine system couples fGSC behavior to multiple environmental cues, such as mating and nutrition.

Generation Covid-19: Should the fetus be worried?

Historically pregnant women and their unborn baby have been amongst those with the poorest outcomes in previous epidemics, most notably the Zika virus. For much of 2020, with the emergence of the novel coronavirus, the effect on the fetus remains unclear. While initial reports suggest that vertical transmission with SARS-CoV2 is reassuringly rare, the complex socioeconomic, domestic and broader maternal lifestyle factors which can influence a child’s lifelong well-being have been modulated during the experience of this pandemic. The developing brain is particularly susceptible to maternal stress, resulting in permanent structural changes and increased incidence of behavioural and mental health illness later in childhood. A large international longitudinal survey is being undertaken by the Department of Psychology to better understand the impact of the pandemic on those yet to be born.

Blood is thicker than water

According to Hamilton’s inclusive fitness hypothesis, kinship is an organizing principle of social behavior. Behavioral evidence supporting this hypothesis includes the ability to recognize kin and the adjustment of behavior based on kin preference with respect to altruism, attachment and care for offspring in insect societies. Despite the fundamental importance of kinship behavior, the underlying neural mechanisms are poorly understood. We repeated behavioral experiments by Hepper on behavioral preference of rats for their kin. Consistent with Hepper’s work, we find a developmental time course for kinship behavior, where rats prefer sibling interactions at young ages and express non-sibling preferences at older ages. In probing the brain areas responsible for this behavior, we find that aspiration lesions of the lateral septum but not control lesions of cingulate cortices eliminate the behavioral preference in young animals for their siblings and in older rats for non-siblings. We then presented awake and anaesthetized rats with odors and calls of age- and status-matched kin (siblings and mothers) and non-kin (non-siblings and non-mothers) conspecifics, while performing in vivo juxta-cellular and whole-cell patch-clamp recordings in the lateral septum. We find multisensory (olfactory and auditory) neuronal responses, whereby neurons typically responded preferentially but not exclusively to individual social stimuli. Non-kin-odor responsive neurons were found dorsally, while kin-odor responsive neurons were located in ventrally in the lateral septum. To our knowledge such an ordered representation of response preferences according to kinship has not been previously observed and we refer this organization as nepotopy. Nepotopy could be instrumental in reading out kinship from preferential but not exclusive responses and in the generation of differential behavior according to kinship. Thus, our results are consistent with a role of the lateral septum in organizing mammalian kinship behavior.

Evaluating different facets of category status for promoting spontaneous transfer

Existing accounts of analogical transfer highlight the importance of comparison-based schema abstraction in aiding retrieval of relevant prior knowledge from memory. In this talk, we discuss an alternative view, the category status hypothesis—which states that if knowledge of a target principle is represented as a relational category, it is easier to activate as a result of categorizing (as opposed to cue-based reminding)—and briefly review supporting evidence. We then further investigate this hypothesis by designing study tasks that promote different facets of category-level representations and assess their impact on spontaneous analogical transfer. A Baseline group compared two analogous cases; the remaining groups experienced comparison plus another task intended to impact the category status of the knowledge representation. The Intension group read an abstract statement of the principle with a supporting task of generating a new case. The Extension group read two more positive cases with the task of judging whether each exemplified the target principle. The Mapping group read a contrast case with the task of revising it into a positive example of the target principle (thereby providing practice moving in both directions between type and token, i.e., evaluating a given case relative to knowledge and using knowledge to generate a revised case). The results demonstrated that both Intension and Extension groups led to transfer improvements over Baseline (with the former demonstrating both improved accessibility of prior knowledge and ability to apply relational concepts). Implications for theories of analogical transfer are discussed.

Neurobiology of Social Behavior

Social interactions are central to the human experience, yet it is also one of the faculty of the brain that is the most impaired by mental illness. Similarly, social interactions are essential for animals to survive, reproduce, and raise their young. Over the years, my lab has attempted to decipher the unique characteristics of social recognition: what are the unique cues that trigger distinct social behaviors, what is the nature and identity of social behavior circuits, how is the function of these circuits different in males and females and how are they modulated by the animal physiological status? In this lecture, I will describe our recent progress in using genetic, imaging, molecular and behavioral approaches to understand how the brain controls specific social behaviors in both males and females, and how areas throughout the brain participate in the positive and negative controls of specific social interactions. I will also describe how new approaches of single cell transcriptomics have enabled us to uncover specific cell populations involved in distinct social behaviors and the basis of their activity modulation according to the animal state.

Swimming in the third domain: archaeal extremophiles

Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to show that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit.

African Neuroscience: Current Status and Prospects

Understanding the function and dysfunction of the brain remains one of the key challenges of our time. However, an overwhelming majority of brain research is carried out in the Global North, by a minority of well-funded and intimately interconnected labs. In contrast, with an estimated one neuroscientist per million people in Africa, news about neuroscience research from the Global South remains sparse. Clearly, devising new policies to boost Africa’s neuroscience landscape is imperative. However, the policy must be based on accurate data, which is largely lacking. Such data must reflect the extreme heterogeneity of research outputs across the continent’s 54 countries. We have analysed all of Africa’s Neuroscience output over the past 21 years and uniquely verified the work performed in African laboratories. Our unique dataset allows us to gain accurate and in-depth information on the current state of African Neuroscience research, and to put it into a global context. The key findings from this work and recommendations on how African research might best be supported in the future will be discussed.

Neuroscience Investigations in the Virgin Lands of African Biodiversity

Africa is blessed with a rich diversity and abundance in rodent and avian populations. This natural endowment on the continent portends research opportunities to study unique anatomical profiles and investigate animal models that may confer better neural architecture to study neurodegenerative diseases, adult neurogenesis, stroke and stem cell therapies. To this end, African researchers are beginning to pay closer attention to some of her indigenous rodents and birds in an attempt to develop spontaneous laboratory models for homegrown neuroscience-based research. For this presentation, I will be showing studies in our lab, involving cellular neuroanatomy of two rodents, the African giant rat (AGR) and Greater cane rat (GCR), Eidolon Bats (EB) and also the Striped Owl (SO). Using histological stains (Cresyl violet and Rapid Golgi) and immunohistochemical biomarkers (GFAP, NeuN, CNPase, Iba-1, Collagen 2, Doublecortin, Ki67, Calbindin, etc), and Electron Microscopy, morphology and functional organizations of neuronal and glial populations of the AGR , GCR, EB and SO brains have been described, with our work ongoing. In addition, the developmental profiles of the prenatal GCR brains have been chronicled across its entire gestational period. Brains of embryos/foetuses were harvested for gross morphological descriptions and then processed using immunofluorescence biomarkers to determine the pattern, onset, duration and peak of neurogenesis (Pax6, Tbr1, Tbr2, NF, HuCD, MAP2) and the onset and peak of glial cell expressions and myelination in the prenatal GCR. The outcome of these research efforts has shown unique neuroanatomical expressions and networks amongst Africa’s rich biodiversity. It is hopeful that continuous effort in this regard will provide sufficient basic research data on neural developments and cellular neuroanatomy with subsequent translational consequences.

The modulation of social decision-making function by dominance status in male mice

COSYNE 2023

Antioxidant effect of combined administration of metformin and propionate in a rat model of type 2 diabetes mellitus

FENS Forum 2024

Comparative study of temporal inflammation pattern of two models of spinal cord injury: Contusion versus transection

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Dynamic integration of space and social status in the mammalian hypothalamus

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Effects of social status on prefrontal and hippocampal structure and function in adult female rhesus macaques

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Epigenetic mechanism affects microglia status and synaptic pruning mechanism

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An ergonomic rodent head fixation apparatus for closed-loop cursor control

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Exacerbation of tauopathy following mild and repeated spinal contusions in the hTauP301S mouse model

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Experience and reactivation status determine engram synapse structural connectivity

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Implication of polyunsaturated fatty acid (PUFA) biostatus in dopamine transmission-related reward processing deficits

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The kainic acid induced status epilepticus: Comparative study of the hippocampus ultrastructure in Wistar rats

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Maternal separation modifies the stress sensitivity, electrophysiology, and morphology of rat nucleus incertus neurons

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Neurochemistry and functional connectivity of the nucleus incertus–ventral hippocampal pathway: Possible involvement in anxiety control in rats and humans

FENS Forum 2024

NGF-sensitive interpeduncular nucleus (IPN) neurons in circuits shaping social behaviour: Anatomical and functional studies of the nucleus incertus–IPN–ventral hippocampus axis

FENS Forum 2024

Pre- and post-treatment with apigenin attenuates status epilepticus-induced neuronal death by reducing oxidative stress and inflammation in the mouse brain

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Retinal ganglion cell type-specific expression and sub-cellular localization of Tusc5/TRARG1 protein in Tusc5EGFP mice

FENS Forum 2024

Role of nucleus incertus in shaping interpeduncular nucleus activity – New neuronal mechanism underlying novelty preference in rats

FENS Forum 2024

Social status impacts peripheral immune responses through synapse strength in prefrontal cortex

FENS Forum 2024

Subchronic administration of the antidiabetic drug metformin mitigates cognitive impairments in a mouse model of type 2 diabetes mellitus

FENS Forum 2024

Training potentiates the efficacy of the adipose-stromal vascular fraction autograft on functional recovery after an acute spinal cord contusion in rats

FENS Forum 2024

TUSC5 role in global and neuronal metabolism

FENS Forum 2024

Unraveling the complexity of stress and reward processing: Nucleus incertus responses to noxious stimulus – electrophysiological, anatomical and immediate early gene expression studies

FENS Forum 2024

Unravelling the complexity of stress and reward processing: The innervation of midbrain nuclei by the nucleus incertus – Anatomical, electrophysiological and behavioural studies in rats

FENS Forum 2024