SISSA Neuroscience department

The Neuroscience Department of the International School for Advanced Studies (SISSA; https://www.sissa.it/research/neuroscience) invites expressions of interest from scientists from various fields of Neuroscience for multiple tenure-track positions with anticipated start in 2025. Ongoing neuroscience research at SISSA includes cognitive neuroscience, computational and theoretical neuroscience, systems neuroscience, molecular and cellular research as well as genomics and genetics. The Department intends to potentiate its activities in these fields and to strengthen cross-field interactions. Expressions of interest from scientists in any of these fields are welcome. The working and teaching language of SISSA is English. This is an equal opportunity career initiative and we encourage applications from qualified women, racial and ethnic minorities, and persons with disabilities. Candidates should have a PhD in a relevant field and a proven record of research achievements. A clear potential to promote and lead research activities, and a specific interest in training and supervising PhD students is essential. Interested colleagues should present an original and innovative plan for their independent future research. We encourage both proposals within existing fields at SISSA as well as novel ideas outside of those or spanning various topics and methodologies of Neuroscience. SISSA is an international school promoting basic and applied research in Neuroscience, Mathematics and Physics and dedicated to the training of PhD students. Lab space and other resources will be commensurate with the appointment. Shared facilities include cell culture rooms, viral vector facilities, confocal microscopes, animal facilities, molecular and biochemical facilities, human cognition labs with EEG, TMS, and eye tracking systems, mechatronics workshop, and computing facilities. Agreements with national and international MRI scanning facilities are also in place. SISSA encourages fruitful exchanges between neuroscientists and other researchers including data scientists, physicists and mathematicians. Interested colleagues are invited to send a single pdf file including a full CV, a brief description of past and future research interests (up to 1,000 words), and the names of three referees to neuro.search@sissa.it. Selected candidates will be invited for an online or in-person seminar and 1- on-1 meetings in summer/autumn 2024. Deadline: A first evaluation round will consider all applications submitted before 15 May 2024. Later applications might be considered if no suitable candidates have been identified yet.

Doctor Mónica Sousa

i3S is looking to recruit a senior researcher with an established international reputation in Neural Cell Biology and strong expertise in securing, managing and leading collaborative research projects and teams/institutional units.

Jens Peter Lindemann

The PhD project is part of the DFG-funded project 'Cue integration by bumblebees during navigation in uncertain environments with multiple goal options: Behavioural analysis in virtual reality and computational modelling' in an international research team. Bumblebees can be trained to prefer certain places or objects in a virtual environment through appropriate rewarding. In a close integration of two PhD projects, one with a focus on VR behaviour experiments and the other focussing on computational modelling and simulation, we are investigating the mechanisms underlying these learning and orientation performances. The applicant is expected to design and implement models for behavioral control of bumblebees, test them in computer simulations, contribute to VR experiments with bumblebees, and collaborate intensively with other project participants.

Antonio C. Roque

The Research, Innovation and Dissemination Center for Neuromathematics (NeuroMat), hosted by the University of São Paulo (USP), Brazil, and funded by the São Paulo Research Foundation (FAPESP), is offering post-doctoral fellowships for recent PhDs with outstanding research potential. The fellowship will involve collaborations with research teams and laboratories associated with NeuroMat. The research to be developed by the post-doc fellow shall be strictly related to ongoing research lines developed by the NeuroMat team that can be consulted at our website. The project may be developed at the laboratories of USP, campuses of São Paulo or Ribeirão Preto, or at UNICAMP, Campinas, in person.

Investigating the Neurobiology and Neurophysiology of Psilocybin Using Drosophila melanogaster as a Model System

The cellular phase of Alzheimer’s Disease and the path towards therapies

Relating circuit dynamics to computation: robustness and dimension-specific computation in cortical dynamics

Neural dynamics represent the hard-to-interpret substrate of circuit computations. Advances in large-scale recordings have highlighted the sheer spatiotemporal complexity of circuit dynamics within and across circuits, portraying in detail the difficulty of interpreting such dynamics and relating it to computation. Indeed, even in extremely simplified experimental conditions, one observes high-dimensional temporal dynamics in the relevant circuits. This complexity can be potentially addressed by the notion that not all changes in population activity have equal meaning, i.e., a small change in the evolution of activity along a particular dimension may have a bigger effect on a given computation than a large change in another. We term such conditions dimension-specific computation. Considering motor preparatory activity in a delayed response task we utilized neural recordings performed simultaneously with optogenetic perturbations to probe circuit dynamics. First, we revealed a remarkable robustness in the detailed evolution of certain dimensions of the population activity, beyond what was thought to be the case experimentally and theoretically. Second, the robust dimension in activity space carries nearly all of the decodable behavioral information whereas other non-robust dimensions contained nearly no decodable information, as if the circuit was setup to make informative dimensions stiff, i.e., resistive to perturbations, leaving uninformative dimensions sloppy, i.e., sensitive to perturbations. Third, we show that this robustness can be achieved by a modular organization of circuitry, whereby modules whose dynamics normally evolve independently can correct each other’s dynamics when an individual module is perturbed, a common design feature in robust systems engineering. Finally, we will recent work extending this framework to understanding the neural dynamics underlying preparation of speech.

Dark Matter in the Locus coeruleus - Neuromelanin in Health and Disease

Examining dexterous motor control in children born with a below elbow deficiency

Brain Emulation Challenge Workshop

Brain Emulation Challenge workshop will tackle cutting-edge topics such as ground-truthing for validation, leveraging artificial datasets generated from virtual brain tissue, and the transformative potential of virtual brain platforms, such as applied to the forthcoming Brain Emulation Challenge.

The Neurobiology of the Addicted Brain

Astrocyte reprogramming / activation and brain homeostasis

Astrocytes are multifunctional glial cells, implicated in neurogenesis and synaptogenesis, supporting and fine-tuning neuronal activity and maintaining brain homeostasis by controlling blood-brain barrier permeability. During the last years a number of studies have shown that astrocytes can also be converted into neurons if they force-express neurogenic transcription factors or miRNAs. Direct astrocytic reprogramming to induced-neurons (iNs) is a powerful approach for manipulating cell fate, as it takes advantage of the intrinsic neural stem cell (NSC) potential of brain resident reactive astrocytes. To this end, astrocytic cell fate conversion to iNs has been well-established in vitro and in vivo using combinations of transcription factors (TFs) or chemical cocktails. Challenging the expression of lineage-specific TFs is accompanied by changes in the expression of miRNAs, that post-transcriptionally modulate high numbers of neurogenesis-promoting factors and have therefore been introduced, supplementary or alternatively to TFs, to instruct direct neuronal reprogramming. The neurogenic miRNA miR-124 has been employed in direct reprogramming protocols supplementary to neurogenic TFs and other miRNAs to enhance direct neurogenic conversion by suppressing multiple non-neuronal targets. In our group we aimed to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own both in vitro and in vivo and elucidate its independent mechanism of reprogramming action. Our in vitro data indicate that miR-124 is a potent driver of the reprogramming switch of astrocytes towards an immature neuronal fate. Elucidation of the molecular pathways being triggered by miR-124 by RNA-seq analysis revealed that miR-124 is sufficient to instruct reprogramming of cortical astrocytes to immature induced-neurons (iNs) in vitro by down-regulating genes with important regulatory roles in astrocytic function. Among these, the RNA binding protein Zfp36l1, implicated in ARE-mediated mRNA decay, was found to be a direct target of miR-124, that be its turn targets neuronal-specific proteins participating in cortical development, which get de-repressed in miR-124-iNs. Furthermore, miR-124 is potent to guide direct neuronal reprogramming of reactive astrocytes to iNs of cortical identity following cortical trauma, a novel finding confirming its robust reprogramming action within the cortical microenvironment under neuroinflammatory conditions. In parallel to their reprogramming properties, astrocytes also participate in the maintenance of blood-brain barrier integrity, which ensures the physiological functioning of the central nervous system and gets affected contributing to the pathology of several neurodegenerative diseases. To study in real time the dynamic physical interactions of astrocytes with brain vasculature under homeostatic and pathological conditions, we performed 2-photon brain intravital imaging in a mouse model of systemic neuroinflammation, known to trigger astrogliosis and microgliosis and to evoke changes in astrocytic contact with brain vasculature. Our in vivo findings indicate that following neuroinflammation the endfeet of activated perivascular astrocytes lose their close proximity and physiological cross-talk with vasculature, however this event is at compensated by the cross-talk of astrocytes with activated microglia, safeguarding blood vessel coverage and maintenance of blood-brain integrity.

How fly neurons compute the direction of visual motion

Detecting the direction of image motion is important for visual navigation, predator avoidance and prey capture, and thus essential for the survival of all animals that have eyes. However, the direction of motion is not explicitly represented at the level of the photoreceptors: it rather needs to be computed by subsequent neural circuits. The exact nature of this process represents a classic example of neural computation and has been a longstanding question in the field. Our results obtained in the fruit fly Drosophila demonstrate that the local direction of motion is computed in two parallel ON and OFF pathways. Within each pathway, a retinotopic array of four direction-selective T4 (ON) and T5 (OFF) cells represents the four Cartesian components of local motion vectors (leftward, rightward, upward, downward). Since none of the presynaptic neurons is directionally selective, direction selectivity first emerges within T4 and T5 cells. Our present research focuses on the cellular and biophysical mechanisms by which the direction of image motion is computed in these neurons.

Mechanisms and Roles of Fast Dopamine Signaling

Dopamine is a neuromodulator that codes information on various time scales. I will discuss recent progress on the identification of fast release mechanisms for dopamine in the mouse striatum. I will present data on triggering mechanisms of dopamine release and evaluate its roles in striatal regulation. In the long-term, our work will allow for a better understanding of the mechanisms and time scales of dopamine coding in health and disease.

How do protein-RNA condensates form and contribute to disease?

In recent years, it has become clear that intrinsically disordered regions (IDRs) of RBPs, and the structure of RNAs, often contribute to the condensation of RNPs. To understand the transcriptomic features of such RNP condensates, we’ve used an improved individual nucleotide resolution CLIP protocol (iiCLIP), which produces highly sensitive and specific data, and thus enables quantitative comparisons of interactions across conditions (Lee et al., 2021). This showed how the IDR-dependent condensation properties of TDP-43 specify its RNA binding and regulatory repertoire (Hallegger et al., 2021). Moreover, we developed software for discovery and visualisation of RNA binding motifs that uncovered common binding patterns of RBPs on long multivalent RNA regions that are composed of dispersed motif clusters (Kuret et al, 2021). Finally, we used hybrid iCLIP (hiCLIP) to characterise the RNA structures mediating the assembly of Staufen RNPs across mammalian brain development, which demonstrated the roles of long-range RNA duplexes in the compaction of long 3’UTRs. I will present how the combined analysis of the characteristics of IDRs in RBPs, multivalent RNA regions and RNA structures is required to understand the formation and functions of RNP condensates, and how they change in diseases.

Charting the Proteome Landscape of Diverse Synapses In Vivo

‘How development sculpts hippocampal circuits’

Acting on our instincts: understanding emotional decision-making

Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.   Our web pages for reference: https://devneuro.org.uk/marinlab/ & https://devneuro.org.uk/rico/default

Determinants of the transition to compulsion in addiction

Single-cell delineation of lineage and genetic identity in the mouse forebrain

Neurobiology of Narcolepsy: effects of the oxytocin system on cataplexy

Linking valence and anxiety in a mouse insula-amygdala circuit

Promising Neuroimmune Targets for Alcohol Use Disorder Pathology

Selectively Silencing Nociceptor Sensory Neurons

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.

Nr4a1 and chromatin bivalency in cocaine pathophysiology

Dual lecture: Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.

Sex Differences in Addiction: lessons from animal models

Transcriptional and Epigenetic Mechanisms of Addiction

The mu opioid receptor and addiction

Selectively Silencing Nociceptor Sensory Neurons

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.

In-Love with Addiction Neuroscience

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.

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.

How do I know my rat is addicted?

D1 and D2 Accumbens Neurons May not be Who You Think They Are:  Distinct tetrapartite synaptic plasticity regulating drug relapse

Neuroimmune and Glutamatergic Mechanisms of Nicotine Addiction

In-Love with Addiction Neuroscience

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.

Tectal and Pretectal Circuits of the Visual Thalamus

Habenular synaptic strength and neuronal dynamics for approach-avoidance behaviours

Acetylcholine dynamics in the basolateral amygdala during reward learning

Neural mechanisms of navigation behavior

The regions of the insect brain devoted to spatial navigation are beautifully orderly, with a remarkably precise pattern of synaptic connections. Thus, we can learn much about the neural mechanisms of spatial navigation by targeting identifiable neurons in these networks for in vivo patch clamp recording and calcium imaging. Our lab has recently discovered that the "compass system" in the Drosophila brain is anchored to not only visual landmarks, but also the prevailing wind direction. Moreover, we found that the compass system can re-learn the relationship between these external sensory cues and internal self-motion cues, via rapid associative synaptic plasticity. Postsynaptic to compass neurons, we found neurons that conjunctively encode heading direction and body-centric translational velocity. We then showed how this representation of travel velocity is transformed from body- to world-centric coordinates at the subsequent layer of the network, two synapses downstream from compass neurons. By integrating this world-centric vector-velocity representation over time, it should be possible for the brain to form a stored representation of the body's path through the environment.

Ready, Set, Go! Neural circuits underlying cognitive control of behavior

The unexpected precision of an activity-dependent transcription factor

Mitochondrial mechanisms in psychostimulant and opioid action

In-Love with Addiction Neuroscience

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.

Dopamine release in the nucleus accumbens core signals perceived saliency

From genetics to neurobiology through transcriptomic data analysis

Over the past years, genetic studies have uncovered hundreds of genetic variants to be associated with complex brain disorders. While this really represents a big step forward in understanding the genetic etiology of brain disorders, the functional interpretation of these variants remains challenging. We aim to help with the functional characterization of variants through transcriptomic data analysis. For instance, we rely on brain transcriptome atlases, such as Allen Brain Atlases, to infer functional relations between genes. One example of this is the identification of signaling mechanisms of steroid receptors. Further, by integrating brain transcriptome atlases with neuropathology and neuroimaging data, we identify key genes and pathways associated with brain disorders (e.g. Parkinson's disease). With technological advances, we can now profile gene expression in single-cells at large scale. These developments have presented significant computational developments. Our lab focuses on developing scalable methods to identify cells in single-cell data through interactive visualization, scalable clustering, classification, and interpretable trajectory modelling. We also work on methods to integrate single-cell data across studies and technologies.

Cellular mechanisms that control state-dependent modulation of sensory processing and plasticity in the cortex

Addiction to cocaine: How you take the drug is more important than how much

Addiction: the compulsive pursuit of a behaviour, not only the drug

New genetically encoded sensors to track addiction-relevant neuromodulators in vivo

Striatal mechanisms underlying vulnerability for punishment-resistant alcohol drinking

Involvement of peptidergic Edinger-Westphal nucleus in the neurobiology of migraine

FENS Forum 2024