Neuroscience seminars

CA3-CA1 synapses in the hippocampus are the initial locus of episodic memory. The action of acetylcholine alters cellular excitability, modifies neuronal networks, and triggers secondary signaling that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model to describe the activation of postsynaptic M1 receptors that leads to IP3 production from membrane PIP2 molecules. The binding of IP3 to IP3 receptors in the endoplasmic reticulum (ER) ultimately causes calcium release. This calcium release from the ER activates potassium channels like the calcium-activated SK channels and alters different aspects of synaptic signaling. In an independent signaling cascade, M1 receptors also directly suppress SK channels and the voltage-activated KCNQ2/3 channels, enhancing post-synaptic excitability. In the CA3 presynaptic terminal, we model the reduction of the voltage sensitivity of voltage-gated calcium channels (VGCCs) and the resulting suppression of neurotransmitter release by the action of the M4 receptors. Our results show that the reduced initial release probability because of acetylcholine alters short-term plasticity (STP) dynamics. We characterize the dichotomy of suppressing neurotransmitter release from CA3 neurons and the enhanced excitability of the postsynaptic CA1 spine. Mechanisms underlying STP operate over a few seconds, while those responsible for LTP last for hours, and both forms of plasticity have been linked with very distinct functions in the brain. We show that the concurrent suppression of neurotransmitter release and increased sensitivity conserves neurotransmitter vesicles and enhances the reliability in plasticity. Our work establishes a relationship between STP and LTP coordinated by neuromodulation with acetylcholine.

Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an increasingly utilized approach for neurological disease modeling with patient-derived cells. Several groups, including ours, have applied the iPSC approach to model severe genetic developmental and epileptic encephalopathies (DEEs) with patient-derived cells. Although most studies to date involve 2-D cultures of patient-derived neurons, brain organoids are increasingly being employed to explore genetic DEE mechanisms. We are applying this approach to understand PMSE (Polyhydramnios, Megalencephaly and Symptomatic Epilepsy) syndrome, Rett Syndrome (in collaboration with Ben Novitch at UCLA) and Protocadherin-19 Clustering Epilepsy (PCE). I will describe our findings of robust structural phenotypes in PMSE and PCE patient-derived brain organoid models, as well as functional abnormalities identified in fusion organoid models of Rett syndrome. In addition to showing epilepsy-relevant phenotypes, both 2D and brain organoid cultures offer platforms to identify novel therapies. We will also discuss challenges and recent advances in the brain organoid field, including a new single rosette brain organoid model that we have developed. The field is advancing rapidly and our findings suggest that brain organoid approaches offers great promise for modeling genetic neurodevelopmental epilepsies and identifying precision therapies.

The integrated conflict monitoring theory of Botvinick introduced cognitive demand into conflict monitoring research. We investigated effects of individual differences of cognitive demand and another determinant of conflict monitoring entitled reinforcement sensitivity on conflict monitoring. We showed evidence of differential variability of conflict monitoring intensity using the electroencephalogram (EEG), functional magnet resonance imaging (fMRI) and behavioral data. Our data suggest that individual differences of anxiety and reasoning ability are differentially related to the recruitment of proactive and reactive cognitive control (cf. Braver). Based on previous findings, the team of the Leue-Lab investigated new psychometric data on conflict monitoring and proactive-reactive cognitive control. Moreover, data of the Leue-Lab suggest the relevance of individual differences of conflict monitoring for the context of deception. In this respect, we plan new studies highlighting individual differences of the functioning of the Anterior Cingulate Cortex (ACC). Disentangling the role of individual differences in working memory-related cognitive demand, mental effort, and reinforcement-related processes opens new insights for cognitive-motivational approaches of information processing (Passcode to rewatch: 0R8v&m59).

The brain is a prediction machine. Yet the world is never entirely predictable, for any animal. Unexpected events are surprising and this typically evokes prediction error signatures in animal brains. In humans such mismatched expectations are often associated with an emotional response as well. Appropriate emotional responses are understood to be important for memory consolidation, suggesting that valence cues more generally constitute an ancient mechanism designed to potently refine and generalize internal models of the world and thereby minimize prediction errors. On the other hand, abolishing error detection and surprise entirely is probably also maladaptive, as this might undermine the very mechanism that brains use to become better prediction machines. This paradoxical view of brain functions as an ongoing tug-of-war between prediction and surprise suggests a compelling new way to study and understand the evolution of consciousness in animals. I will present approaches to studying attention and prediction in the tiny brain of the fruit fly, Drosophila melanogaster. I will discuss how an ‘active’ sleep stage (termed rapid eye movement – REM – sleep in mammals) may have evolved in the first animal brains as a mechanism for optimizing prediction in motile creatures confronted with constantly changing environments. A role for REM sleep in emotional regulation could thus be better understood as an ancient sleep function that evolved alongside selective attention to maintain an adaptive balance between prediction and surprise. This view of active sleep has some interesting implications for the evolution of subjective awareness and consciousness.

Colour vision plays important roles in regulating animal behaviour, yet understanding of how such information is processed in the brain is still incomplete. Here I discuss our work addressing this issue in mice where, despite aspects of retinal organisation that might suggest limited capacity for colour vision, we find evidence of extensive cone-dependent spectral opponency across subcortical visual centres. In particular, our data both reveals important contributions of such colour signals to non-image-forming functions (regulation of the circadian system) but also indicate surprisingly sophisticated support for more conventional aspects of colour vision.

Several excellent computational frameworks exist that enable high-throughput and consistent tracking of freely moving unmarked animals. SimBA introduce and distribute a plug-and play pipeline that enables users to use these pose-estimation approaches in combination with behavioral annotation for the generation of supervised machine-learning behavioral predictive classifiers. SimBA was developed for the analysis of complex social behaviors, but includes the flexibility for users to generate predictive classifiers across other behavioral modalities with minimal effort and no specialized computational background. SimBA has a variety of extended functions for large scale batch video pre-processing, generating descriptive statistics from movement features, and interactive modules for user-defined regions of interest and visualizing classification probabilities and movement patterns.

In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.

Recent success in training artificial agents and robots derives from a combination of direct learning of behavioral policies and indirect learning via value functions. Policy learning and value learning employ distinct algorithms that depend upon evaluation of errors in performance and reward prediction errors, respectively. In mammals, behavioral learning and the role of mesolimbic dopamine signaling have been extensively evaluated with respect to reward prediction errors; but there has been little consideration of how direct policy learning might inform our understanding. I’ll discuss our recent work on classical conditioning in naïve mice (https://www.biorxiv.org/content/10.1101/2021.05.31.446464v1) that provides multiple lines of evidence that phasic dopamine signaling regulates policy learning from performance errors in addition to its well-known roles in value learning. This work points towards new opportunities for unraveling the mechanisms of basal ganglia control over behavior under both adaptive and maladaptive learning conditions.

Many studies have investigated the major glutamatergic inputs to the cerebellum, mossy fibres and climbing fibres, however far less is known about its neuromodulatory inputs. In particular, anatomical studies have described cholinergic input to the cerebellum, yet little is known about its role(s). In this talk, I will present our recent findings which demonstrate that manipulating acetylcholine receptors in the cerebellum causes effects at both a cellular and behavioural level. Activating acetylcholine receptors alters the intrinsic properties and synaptic inputs of cerebellar output neurons, and blocking these receptors results in deficits in a range of behavioural tasks.

How inclusive and diverse is non-invasive brain stimulation in the treatment of psychiatric disorders?Indira Tendolkar, Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry. Mental illness is associated with a huge socioeconomic burden worldwide, with annual costs only in the Netherlands of €22 billion. Over two decades of cognitive and affective neuroscience research with modern tools of neuroimaging and neurophysiology in humans have given us a wealth of information about neural circuits underlying the main symptom domains of psychiatric disorders and their remediation. Neuromodulation entails the alteration of these neural circuits through invasive (e.g., DBS) or non-invasive (e.g., TMS) techniques with the aim of improving symptoms and/or functions and enhancing neuroplasticity. In my talk, I will focus on neuromodulation studies using repetitive transcranial magnetic stimulation (rTMS) as a relatively safe, noninvasive method, which can be performed simultaneously with neurocognitive interventions. Using the examples of two chronifying mental illnesses, namely obsessive compulsive disorders and major depressive disorder (MDD), I will review the concept of "state dependent" effects of rTMS and highlight how simultaneous or sequential cognitive interventions could help optimize rTMS therapy by providing further control of ongoing neural activity in targeted neural networks. Hardly any attention has been paid to diversity aspects in the studies. By including studies from low- and middle income countries, I will discuss the potential of non-invasive brain stimulation from a transcultural perspective.

“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.”

In recent years, communicating one’s research to audiences outside of academia has grown in importance and time commitment for many researchers. Science Slams or University Open Days reliably draw large crowds, and the potential of social media to amplify any message has made it possible to reach interested recipients without the traditional press as a middleman. In this presentation, I will provide insights into science communication from my perspective as a neuroscience researcher, who enjoys spreading the word about how amazing insect brains are. We will have a look at the What?, Why? and How? of science communication. What do we generally mean by the term, and what forms can it take? Why should – or must – we engage in it? And how can we best achieve our aims with it? I will provide an overview of the current communication landscape, some food for (critical) thought, and many practical tips that help me when preparing to share my science with a wider audience.

Detection of motion is essential for survival, but how the visual system processes moving stimuli is not fully understood. Here, based on a detailed analysis of glutamate release from bipolar cells, we outline the rules that govern the representation of object motion in the early processing stages. Our main findings are as follows: (1) Motion processing begins already at the first retinal synapse. (2) The shape and the amplitude of motion responses cannot be reliably predicted from bipolar cell responses to stationary objects. (3) Enhanced representation of novel objects - particularly in bipolar cells with transient dynamics. (4) Response amplitude in bipolar cells matches visual salience reported in humans: suddenly appearing objects > novel motion > existing motion. These findings can be explained by antagonistic interactions in the center-surround receptive field, demonstrate that despite their simple operational concepts, classical center-surround receptive fields enable sophisticated visual computations.

A diverse mix of neurotechnology talks from academic and industry colleagues plus presentations from our MRes Neurotechnology students. Visit our event page to find out more and register now!