Photometry
photometry
Nikolas Karalis
We are seeking a passionate and dedicated research technician to join our team Neuronal Circuits & Brain Dynamics at the Paris Brain Institute (ICM). Our work focuses on unraveling the fascinating mysteries of how the brain generates internal states and how neuromodulators, such as dopamine and serotonin, influence neuronal activity during behavior. To achieve our goals, we employ state-of-the-art techniques, including behavioral, optogenetic, imaging, electrophysiological, and genetic approaches in mice. Main Responsibilities • As a research technician, you are at the epicenter of our research activities and you will serve as a point of reference of the lab know-how across generations of lab members. • As a hands-on research technician, your primary responsibilities will include organizing the laboratory, maintaining basic lab infrastructure, performing routine tasks, regularly updating lab databases, ensuring the lab runs efficiently, and contributing to the team's research efforts. • Collaborating closely with the team, you will contribute to ongoing research projects and you will conduct behavioral and optogenetic experiments, carry out stereotaxic surgeries, and handle histological processing, including tissue slicing, immunostaining, and fluorescent microscopy. • You will be responsible for learning, developing, and passing on Standard Operating Procedures (SOPs) for the techniques utilized in our lab. • Additionally, in coordination with the head of the animal facility, you will supervise and ensure adherence to animal welfare guidelines, as well as maintain project permits and annual reports. • This role provides the opportunity to lead and participate in research projects to the extent of your desire. We offer competitive compensation and benefits within an interactive, interdisciplinary working environment, where cutting-edge science thrives and a dynamic, international research community awaits. As part of your role, you will receive extensive training in traditional and cutting-edge neuroscience techniques related to mice. If you are eager to join our vibrant research community and contribute to groundbreaking discoveries, we warmly welcome your application. The position is available immediately, with the potential for a permanent contract based on performance. If you would like to know more, visit our website: neuronaldynamics.eu and read about our team's mission and values. Why join our team • We are a young and vibrant group of scientists, fueled by curiosity and passion for understanding the brain. • We work as a team and use or invent cutting-edge neurotechnologies to answer fundamental questions in neuroscience. • Our team is committed to the training, mentorship, and career development of the next generation of neuroscientists. To achieve that, we foster an inclusive and supportive environment, where we can learn and advance science while having fun in the process. • Our work is multi-disciplinary, and so is our team. Irrespective of your background and project, our research environment will expose you to a diverse range of experimental and computational aspects of systems and circuits neuroscience. We thus encourage everyone to apply, especially those from underrepresented minorities. • Our team is affiliated with Inserm and is located in the Paris Brain Institute (ICM), where we have access to state-of-the-art facilities and resources. • Our vibrant community at the ICM and throughout Paris promotes broad collaboration and learning opportunities. <b>How to apply</b> If you are eager to join our vibrant research community and contribute to groundbreaking discoveries, we warmly welcome your application. The position is available immediately, with the potential for a permanent contract based on performance. Please send a statement of your past work and interests, your CV, and contact information for 1-3 references to the address: contact@neuronaldynamics.eu
Nikolas Karalis
We invite applications for postdoctoral researchers to join our team Neuronal Circuits & Brain Dynamics at the Paris Brain Institute (ICM) to study the principles of neuronal circuit organization and brain dynamics. If you are an ambitious and driven researcher, interested in experimental or computational systems and circuits neuroscience, and seeking an environment that fosters intellectual and professional growth, we invite you to consider joining our team. Together, we'll make a lasting impact on science and pave the way for your successful research career. Our team values diversity and welcomes researchers from all backgrounds and profiles. If your project ideas align with our research focus, we encourage you to get in touch with us. Research Topics We are interested in how neuronal circuits are organized and how the collective action of neurons gives rise to the emergent complex brain dynamics and behavior. We focus on how neurochemicals and bodily signals influence the brain. * We study how the simultaneous release of neuromodulators influences the activity of neurons and the coordination of brain regions * We also study how bodily signals, such as breathing, serve as fundamental elements of the oscillatory circuit architecture * We employ our approach to study the brain dynamics during behavior and sleep and their involvement in the transformation of fleeting experiences into long-term memories To answer these fundamental questions about the nature and function of the brain, we combine a range of cutting-edge neurotechnologies that enable us to observe and control the activity of the brain. We aim to identify and explore the fundamental principles of neural circuit organization and apply our understanding for the improvement of the human condition. Pure experimental, as well as computational/theoretical, or hybrid projects are available, depending on your interest and skills. Opportunities As a postdoctoral researcher in our group: • You will be an integral part of shaping our research direction and team culture. You will engage in exciting and meaningful research and will have access to all the tools necessary to push the boundaries of scientific exploration, with our cutting-edge techniques and state-of-the-art facilities. • You will have the opportunity to mentor graduate and master's students. This role enhances your leadership and communication skills while you contribute to the growth of the next generation of scientists. By guiding and collaborating with these aspiring researchers, you contribute to the collective knowledge and expertise of the team. Mentoring fosters a supportive and enriching atmosphere that reduces the mental strain of working alone on a project, as you can share ideas, problem-solve together, and gain fresh perspectives. • You will have ample opportunities to develop vital skills for your future academic career, such as mentoring, grant writing, presenting your work, publishing papers, and leading projects to completion. In parallel, you will gain invaluable first-hand experience in setting up and managing a young research team. • We encourage participation in conferences and workshops, where you can present your research findings to the wider scientific community. Why join our team • We are a young and vibrant group of scientists, fueled by curiosity and passion for understanding the brain. We work as a team and use or invent cutting-edge neurotechnologies to answer fundamental questions in neuroscience. • Our team is committed to the training, mentorship, and career development of the next generation of neuroscientists. To achieve that, we foster an inclusive and supportive environment, where we can learn and advance science while having fun in the process. • Our work is multi-disciplinary, and so is our team. Irrespective of your background and project, our research environment will expose you to a diverse range of experimental and computational aspects of systems and circuits neuroscience. We thus encourage everyone to apply, especially those from underrepresented minorities. • Working in our team will provide you with invaluable experience across all stages of research and you will have the opportunity to engage in experiment design and execution, method development, software design, and data analysis, as well as publishing and communicating research results. • Our team is affiliated with Inserm and is located in the Paris Brain Institute (ICM), where we have access to state-of-the-art facilities and resources. • Our vibrant community at the ICM and throughout Paris promotes broad collaboration and learning opportunities.
Nikolas Karalis
If you are a data scientist, programmer, or engineer, with a keen interest in helping to understand the brain, consider joining our team Neuronal Circuits & Brain Dynamics at the Paris Brain Institute (ICM). We study the principles of neuronal circuit organization and brain dynamics. Our work focuses on unraveling the fascinating mysteries of how the brain generates internal states and how neuromodulators, such as dopamine and serotonin, influence neuronal activity and communication between brain regions during behavior. To achieve our goals, we perform large-scale recordings from thousands of neurons simultaneously using multimodal recordings, including electrophysiological or optical imaging approaches. We employ state-of-the-art techniques, including behavioral, optogenetic, imaging, electrophysiological, and genetic approaches in mice to record and manipulate the brain activity during behavior. Using this unprecedented data, we will be able to understand information flow in the brain in ways that would be unimaginable only a few years ago. However, the scale and complexity of this data provide major challenges and unique opportunities. We are looking for computationally-orientated researchers to join our team as temporary or permanent staff members, to help us develop methods to interact and analyze our multi-dimensional neurophysiological and behavioral data, and to develop innovative analysis approaches and efficient processing pipelines, to accelerate the progress of our research on our path to understanding the brain. As a data analyst in our group, you will interact closely with experimentalists and contribute crucially to the research. Our team values diversity and welcomes researchers from all backgrounds and profiles. If your profile aligns with our research needs, we encourage you to get in touch with us. Main responsibilities • Organize data management pipeline • Analyze neurophysiological and behavioral data • Develop analysis methods and software tools to facilitate the analysis of multi-modal and multi-dimensional neurophysiological data • Implement cutting-edge data science approaches (statistical, computational, and ML) for complex neuroscience problems • Create robust and efficient data pipelines to extract, transform, and visualize data • Develop, test, and implement scientific software (e.g., for reproducible analysis pipelines and data storage) • Interact with experimentalists to design experiments and implement analyses • Analyze current technologies, algorithms, models, and methods • As part of your role, you will have the opportunity to collaborate with other teams, attend trainings, mentor students, have independent projects, and present at major relevant conferences (Cosyne, NeurIPS). We offer competitive compensation and benefits within an interactive, interdisciplinary working environment, where cutting-edge science thrives and a dynamic, international research community awaits.
Combined electrophysiological and optical recording of multi-scale neural circuit dynamics
This webinar will showcase new approaches for electrophysiological recordings using our silicon neural probes and surface arrays combined with diverse optical methods such as wide-field or 2-photon imaging, fiber photometry, and optogenetic perturbations in awake, behaving mice. Multi-modal recording of single units and local field potentials across cortex, hippocampus and thalamus alongside calcium activity via GCaMP6F in cortical neurons in triple-transgenic animals or in hippocampal astrocytes via viral transduction are brought to bear to reveal hitherto inaccessible and under-appreciated aspects of coordinated dynamics in the brain.
Identifying central mechanisms of glucocorticoid circadian rhythm dysfunction in breast cancer
The circadian release of endogenous glucocorticoids is essential in preparing and synchronizing the body’s daily physiological needs. Disruption in the rhythmic activity of glucocorticoids has been observed in individuals with a variety of cancer types, and blunting of this rhythm has been shown to predict cancer mortality and declines in quality of life. This suggests that a disrupted glucocorticoid rhythm is potentially a shared phenotype across cancers. However, where this phenomenon is driven by the cancer itself, and the causal mechanisms that link glucocorticoid rhythm dysfunction and cancer outcomes remain preliminary at best. The regulation of daily glucocorticoid activity has been well-characterized and is maintained, in part, by the coordinated response of the hypothalamic-pituitary-adrenal (HPA) axis, consisting of the suprachiasmatic nucleus (SCN) and corticotropin-releasing hormone-expressing neurons of the paraventricular nucleus of the hypothalamus (PVNCRH). Consequently, we set out to examine if cancer-induced glucocorticoid dysfunction is regulated by disruptions within these hypothalamic nuclei. In comparison to their tumor-free baseline, mammary tumor-bearing mice exhibited a blunting of glucocorticoid rhythms across multiple timepoints throughout the day, as measured by the overall levels and the slope of fecal corticosterone rhythms, during tumor progression. We further examined how peripheral tumors shape hypothalamic activity within the brain. Serial two-photon tomography for whole-brain cFos imaging suggests a disrupted activation of the PVN in mice with tumors. Additionally, we found GFP labeled CRH+ neurons within the PVN after injection of pseudorabies virus expressing GFP into the tumor, pointing to the PVN as a primary target disrupted by mammary tumors. Preliminary in vivo fiber photometry data show that PVNCRH neurons exhibit enhanced calcium activity during tumor progression, as compared to baseline (no tumor) activity. Taken together, this suggests that there may be an overactive HPA response during tumor progression, which in turn, may result in a subsequent negative feedback on glucocorticoid rhythms. Current studies are examining whether tumor progression modulates SCN calcium activity, how the transcriptional profile of PVNCRH neurons is changed, and test if manipulation of the neurocircuitry surrounding glucocorticoid rhythmicity alters tumor characteristics.
Dynamic dopaminergic signaling probabilistically controls the timing of self-timed movements
Human movement disorders and pharmacological studies have long suggested molecular dopamine modulates the pace of the internal clock. But how does the endogenous dopaminergic system influence the timing of our movements? We examined the relationship between dopaminergic signaling and the timing of reward-related, self-timed movements in mice. Animals were trained to initiate licking after a self-timed interval following a start cue; reward was delivered if the animal’s first lick fell within a rewarded window (3.3-7 s). The first-lick timing distributions exhibited the scalar property, and we leveraged the considerable variability in these distributions to determine how the activity of the dopaminergic system related to the animals’ timing. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time, even on single trials. Steeply rising signals preceded early initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movement. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of the timing distribution, whereas inhibition caused late-shifting, as if dopaminergic manipulation modulated the moment-to-moment probability of unleashing the planned movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation. We conclude that ramping dopaminergic signals, potentially encoding dynamic reward expectation, probabilistically modulate the moment-by-moment decision of when to move. (Based on work from Hamilos et al., eLife, 2021).
Dissecting the role of accumbal D1 and D2 medium spiny neurons in information encoding
Nearly all motivated behaviors require the ability to associate outcomes with specific actions and make adaptive decisions about future behavior. The nucleus accumbens (NAc) is integrally involved in these processes. The NAc is a heterogeneous population primarily composed of D1 and D2 medium spiny projection (MSN) neurons that are thought to have opposed roles in behavior, with D1 MSNs promoting reward and D2 MSNs promoting aversion. Here we examined what types of information are encoded by the D1 and D2 MSNs using optogenetics, fiber photometry, and cellular resolution calcium imaging. First, we showed that mice responded for optical self-stimulation of both cell types, suggesting D2-MSN activation is not inherently aversive. Next, we recorded population and single cell activity patterns of D1 and D2 MSNs during reinforcement as well as Pavlovian learning paradigms that allow dissociation of stimulus value, outcome, cue learning, and action. We demonstrated that D1 MSNs respond to the presence and intensity of unconditioned stimuli – regardless of value. Conversely, D2 MSNs responded to the prediction of these outcomes during specific cues. Overall, these results provide foundational evidence for the discrete aspects of information that are encoded within the NAc D1 and D2 MSN populations. These results will significantly enhance our understanding of the involvement of the NAc MSNs in learning and memory as well as how these neurons contribute to the development and maintenance of substance use disorders.
GuPPy, a Python toolbox for the analysis of fiber photometry data
Fiber photometry (FP) is an adaptable method for recording in vivo neural activity in freely behaving animals. It has become a popular tool in neuroscience due to its ease of use, low cost, the ability to combine FP with freely moving behavior, among other advantages. However, analysis of FP data can be a challenge for new users, especially those with a limited programming background. Here, we present Guided Photometry Analysis in Python (GuPPy), a free and open-source FP analysis tool. GuPPy is provided as a Jupyter notebook, a well-commented interactive development environment (IDE) designed to operate across platforms. GuPPy presents the user with a set of graphic user interfaces (GUIs) to load data and provide input parameters. Graphs produced by GuPPy can be exported into various image formats for integration into scientific figures. As an open-source tool, GuPPy can be modified by users with knowledge of Python to fit their specific needs.
A brain circuit for curiosity
Motivational drives are internal states that can be different even in similar interactions with external stimuli. Curiosity as the motivational drive for novelty-seeking and investigating the surrounding environment is for survival as essential and intrinsic as hunger. Curiosity, hunger, and appetitive aggression drive three different goal-directed behaviors—novelty seeking, food eating, and hunting— but these behaviors are composed of similar actions in animals. This similarity of actions has made it challenging to study novelty seeking and distinguish it from eating and hunting in nonarticulating animals. The brain mechanisms underlying this basic survival drive, curiosity, and novelty-seeking behavior have remained unclear. In spite of having well-developed techniques to study mouse brain circuits, there are many controversial and different results in the field of motivational behavior. This has left the functions of motivational brain regions such as the zona incerta (ZI) still uncertain. Not having a transparent, nonreinforced, and easily replicable paradigm is one of the main causes of this uncertainty. Therefore, we chose a simple solution to conduct our research: giving the mouse freedom to choose what it wants—double freeaccess choice. By examining mice in an experimental battery of object free-access double-choice (FADC) and social interaction tests—using optogenetics, chemogenetics, calcium fiber photometry, multichannel recording electrophysiology, and multicolor mRNA in situ hybridization—we uncovered a cell type–specific cortico-subcortical brain circuit of the curiosity and novelty-seeking behavior. We found in mice that inhibitory neurons in the medial ZI (ZIm) are essential for the decision to investigate an object or a conspecific. These neurons receive excitatory input from the prelimbic cortex to signal the initiation of exploration. This signal is modulated in the ZIm by the level of investigatory motivation. Increased activity in the ZIm instigates deep investigative action by inhibiting the periaqueductal gray region. A subpopulation of inhibitory ZIm neurons expressing tachykinin 1 (TAC1) modulates the investigatory behavior.
Characterization of transcranial focused ultrasound stimulation using calcium imaging with fiber photometry in mice
FENS Forum 2024
Fused Fiber Photometry 2.0: A flexible and versatile system for multi-color fiber photometry and optogenetic manipulation
FENS Forum 2024
Integrated electrophysiology and fiber photometry examination of the prefrontal cortex in the mouse model of implicit learning
FENS Forum 2024
Label-free biomolecular spectroscopy with vibrational fiber photometry deep in the mouse brain
FENS Forum 2024
Waveform sampling-based fluorescence lifetime fiber photometry (FLiP) measurements
FENS Forum 2024