Neuroscience seminars

Classification of neurons, long viewed as a fairly boring enterprise, has emerged as a major bottleneck in analysis of neural circuits. High throughput single cell RNA-seq has provided a new way to improve the situation. We initially applied this method to mouse retina, showing that its five neuronal classes (photoreceptors, three groups of interneurons, and retinal ganglion cells) can be divided into 130 discrete types. We then applied the method to other species including human, macaque, zebrafish and chick. With the atlases in hand, we are now using them to address questions about how retinal cell types diversify, how they differ in their responses to injury and disease, and the extent to which cell classes and types are conserved among vertebrates.

To build an appropriate representation of the sensory stimuli around the world, neural circuits are wired according to both intrinsic factors and external sensory stimuli. Moreover, the brain circuits have the capacity to rewire in response to altered environment, both during early development and throughout life. In this talk, I will give an overview about my past research in studying the dynamic processes underlying functional maturation and plasticity in rodent sensory cortices. I will also present data about the current and future research in my lab – that is, the synaptic and circuit mechanisms by which the mature brain circuits employ to regulate the balance between stability and plasticity. By applying chronic 2-photon calcium and close-loop visual exposure, we studied the circuit changes at single-neuron resolution to show that concurrent running with visual stimulus is required to drive neuroplasticity in the adult brain.

Our first NeurotechEU Summit will be fully digital and will take place on November 22th from 09:00 to 17:00 (CET). The final programme can be downloaded here. Hosted by the Karolinska Institutet, the summit will provide you an overview of our actions and achievements from the last year and introduce the priorities for the next year. You will also have the opportunity to attend the finals of the 3 minute thesis competition (3MT) organized by the Synapses Student Society, the student charter of NeurotechEU. Good luck to all the finalists: Lynn Le, Robin Noordhof, Adriana Gea González, Juan Carranza Valencia, Lea van Husen, Guoming (Tony) Man, Lilly Pitshaporn Leelaarporn, Cemre Su, Kaya Keleş, Ramazan Tarık Türksoy, Cristiana Tisca, Sara Bandiera, Irina Maria Vlad, Iulia Vadan, Borbála László, and David Papp! Don’t miss our keynote lecture, success stories and interactive discussions with Ms Vanessa Debiais Sainton (Head of Higher Education Unit, European Commission), Prof. Staffan Holmin (Karolinska Institutet), Dr Mohsen Kaboli (BMW Group, member of the NeurotechEU Associates Advisory Committee), and Prof. Peter Hagoort (Max Planck Institute for Psycholinguistics, Donders Institute). Would you like to use this opportunity to network? Please join our informal breakout sessions on Wonder.me at 11:40 CET. You will be able to move from one discussion group to another within 3 sessions: NeurotechEU ecosystem - The Associates Advisory Committee: Synergies in cross-sectoral initiatives Education next: Trans-European education and the European Universities Initiatives - Lessons learned thus far. Equality, diversity and inclusion at NeurotechEU: removing access barriers to education and developing a working, learning, and social environment where everyone is respected and valued. You can register for this free event at www.crowdcast.io/e/neurotecheu-summit

Sleep is classically presented as an all-or-nothing phenomenon. Yet, there is increasing evidence showing that sleep and wakefulness can actually intermingle and that wake-like and sleep-like activity can be observed concomitantly in different brain regions. I will here explore the implications of this conception of sleep as a local phenomenon for cognition and consciousness. In the first part of my presentation, I will show how local modulations of sleep depth during sleep could support the processing of sensory information by sleepers. I will also how, under certain circumstances, sleepers can learn while sleeping but also how they can forget. In the second part, I will show how the reverse phenomenon, sleep intrusions during waking, can explain modulations of attention. I will focus in particular on modulations of subjective experience and how the local sleep framework can inform our understanding of everyday phenomena such as mind wandering and mind blanking. Through this presentation and the exploration of both sleep and wakefulness, I will seek to connect changes in neurophysiology with changes in behaviour and subjective experience.

Behavior relies on the ability of sensory systems to infer changing properties of the environment from incoming sensory stimuli. However, the demands that detecting and adjusting to changes in the environment place on a sensory system often differ from the demands associated with performing a specific behavioral task. This necessitates neural coding strategies that can dynamically balance these conflicting needs. I will discuss our ongoing theoretical work to understand how this balance can best be achieved. We connect ideas from efficient coding and Bayesian inference to ask how sensory systems should dynamically allocate limited resources when the goal is to optimally infer changing latent states of the environment, rather than reconstruct incoming stimuli. We use these ideas to explore dynamic tradeoffs between the efficiency and speed of sensory adaptation schemes, and the downstream computations that these schemes might support. Finally, we derive families of codes that balance these competing objectives, and we demonstrate their close match to experimentally-observed neural dynamics during sensory adaptation. These results provide a unifying perspective on adaptive neural dynamics across a range of sensory systems, environments, and sensory tasks.

How our senses work both separately and together involves rich computational problems. I will discuss the spatial and representational problems faced by the visual and auditory system, focusing on two issues. 1. How does the brain correct for discrepancies in the visual and auditory spatial reference frames? I will describe our recent discovery of a novel type of otoacoustic emission, the eye movement related eardrum oscillation, or EMREO (Gruters et al, PNAS 2018). 2. How does the brain encode more than one stimulus at a time? I will discuss evidence for neural time-division multiplexing, in which neural activity fluctuates across time to allow representations to encode more than one simultaneous stimulus (Caruso et al, Nat Comm 2018). These findings all emerged from experimentally testing computational models regarding spatial representations and their transformations within and across sensory pathways. Further, they speak to several general problems confronting modern neuroscience such as the hierarchical organization of brain pathways and limits on perceptual/cognitive processing.

In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.

There is an avalanche of new data on activity in neural networks and the biological brain, revealing the collective dynamics of vast numbers of neurons. In principle, these collective dynamics can be of almost arbitrarily high dimension, with many independent degrees of freedom — and this may reflect powerful capacities for general computing or information. In practice, neural datasets reveal a range of outcomes, including collective dynamics of much lower dimension — and this may reflect other desiderata for neural codes. For what networks does each case occur? We begin by exploring bottom-up mechanistic ideas that link tractable statistical properties of network connectivity with the dimension of the activity that they produce. We then cover “top-down” ideas that describe how features of connectivity and dynamics that impact dimension arise as networks learn to perform fundamental computational tasks.

Recent breakthroughs in neurobiology indicate that time is ripe to understand the cellular-level mechanisms of conscious experience. Accordingly, we have recently proposed that conscious processing depends on the integration between top-down and bottom-up information streams and that there exists a specific cellular mechanism that gates this integration. I will first describe this cellular mechanism and demonstrate how it controls signal propagation within the thalamocortical system. Then I will show how this cellular-level mechanism provides a natural explanation for why conscious experience is modulated by top-down processing. Besides shining new light on the neural basis of consciousness, this perspective unravels the mechanisms of internally generated perception, such as dreams, imagery, and hallucinations.

Local anesthetics decrease the excitability of all neurons by blocking voltage-gated sodium channels non-selectively. We have developed a technology to silence only those sensory neurons – the nociceptors – that trigger pain, itch, and cough. I will tell you why and how we devised the strategy, the way we showed that it works, and will also discuss its implications for treating multiple human disorders.

Menstruation is a normal physiological process in women occurring as a result of changes in two ovarian produced hormones – estrogen and progesterone. As a result of these fluctuations, women experience different symptoms in their bodies – their immune system changes (Sekigawa et al, 2004), there are changes in their cardiovascular and digestive system (Millikan, 2006), as well as skin (Hall and Phillips, 2005). But these hormone fluctuations produce major changes in their behavioral pattern as well causing: anxiety, sadness, heightened irritability and anger (Severino and Moline, 1995) which is usually classified as premenstrual syndrome (PMS). In some cases these symptoms severely impair women’s lives and professional help is required. The official diagnosis according to DSM-5 (2013) is premenstrual dysphoric disorder (PMDD). Despite its ubiquitous presence the origins of PMS and PMDD are poorly understood. Some efforts to understand the underlying brain state during the menstruation cycle were performed by using TMS (Smith et al, 1999; 2002; 2003; Inghilleri et al, 2004; Hausmann et al, 2006). But all of these experiments suffer from major shortcomings - no control groups and small number of subjects. Our plan is to address all of these shortcomings and make this the biggest (to our knowledge) experiment of its kind which will, hopefully, provide us with some much needed answers.

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our find- ings thus extend theta phase precession to humans and suggest that this phenomenon has a broad func- tional role for the neural representation of both spatial and non-spatial information.

The Hsieh lab focuses on the mechanisms that promote neural stem cell self-renewal and differentiation in embryonic and adult brain. Using mouse models, video-EEG monitoring, viral techniques, and imaging/electrophysiological approaches, we elucidated many of the key transcriptional/epigenetic regulators of adult neurogenesis and showed aberrant new neuron integration in adult rodent hippocampus contribute to circuit disruption and seizure development. Building on this work, I will present our recent studies describing how GABA-mediated Ca2+ activity regulates the production of aberrant adult-born granule cells. In a new direction of my laboratory, we are using human induced pluripotent stem cells and brain organoid models as approaches to understand brain development and disease. Mutations in one gene, Aristaless-related homeobox (ARX), are of considerable interest since they are known to cause a common spectrum of neurodevelopmental disorders including epilepsy, autism, and intellectual disability. We have generated cortical and subpallial organoids from patients with poly-alanine expansion mutations in ARX. To understand the nature of ARX mutations in the organoid system, we are currently performing cellular, molecular, and physiological analyses. I will present these data to gain a comprehensive picture of the effect of ARX mutations in brain development. Since we do not understand how human brain development is affected by ARX mutations that contribute to epilepsy, we believe these studies will allow us to understand the mechanism of pathogenesis of ARX mutations, which has the potential to impact the diagnosis and care of patients.

In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you can’t befriend everybody you meet, nor can every neuron wire with every other!). This talk will cover some of Alex’s work showing that microscopic (cellular scale) brain networks inferred from spontaneous activity show similar complex topology to that previously described in macroscopic human brain scans. The talk will also discuss what happens when neurodevelopment is disrupted in the case of a monogenic disorder called Rett Syndrome. This will include simulations of neuronal activity and the effects of manipulation of model parameters as well as what happens when we manipulate real developing networks using optogenetics. If functional development can be restored in atypical networks, this may have implications for treatment of neurodevelopmental disorders like Rett Syndrome.

In this talk I’ll discuss our recent work on how visual and auditory cues to space are integrated as we move. There are at least 3 reasons why this turns out to be a difficult problem for the brain to solve (and us to understand!). First, vision and hearing start off in different coordinates (eye-centred vs head-centred), so they need a common reference frame in which to communicate. By preventing eye and head movements, this problem has been neatly sidestepped in the literature, yet self-movement is the norm. Second, self-movement creates visual and auditory image motion. Correct interpretation therefore requires some form of compensation. Third, vision and hearing encode motion in very different ways: vision contains dedicated motion detectors sensitive to speed, whereas hearing does not. We propose that some (all?) of these problems could be solved by considering the perception of audiovisual space as the integration of separate body-centred visual and auditory cues, the latter formed by integrating image motion with motor system signals and vestibular information. To test this claim, we use a classic cue integration framework, modified to account for cues that are biased and partially correlated. We find good evidence for the model based on simple judgements of audiovisual motion within a circular array of speakers and LEDs that surround the participant while they execute self-controlled head movement.

Neuronal dendritic trees display a wide range of nonlinear input integrations due to their voltage-dependent active calcium channels. We reveal that in vivo-like fluctuating input enhances nonlinearity substantially in a single dendritic compartment and shifts the input-output relation to exhibiting nonmonotonous or bistable dynamics. In particular, with the slow activation of calcium dynamics, we analyze noise-induced bistability and its timescales. We show bistability induces long-timescale fluctuation that can account for observed dendritic plateau potentials in vivo conditions. In a multicompartmental model neuron with realistic synaptic input, we show that noise-induced bistability persists in a wide range of parameters. Using Fredholm's theory to calculate the spiking rate of multivariable neurons, we discuss how dendritic bistability shifts the spiking dynamics of single neurons and its implications for network phenomena in the processing of in vivo–like fluctuating input.