localization

National Institute of Allergy and Infectious Diseases

The role of endogenous chimeric mRNA encoded GasderminD fusion proteins in immunity

May 31, 2031

Project Summary: Programmed inflammatory cell death, or pyroptosis, is a crucial innate defense mechanism that protects hosts against infection and orchestrates subsequent immune responses. Central to this process is Gasdermin D (GSDMD), a protein that forms plasma membrane pores upon activation, enabling the release of pro- inflammatory cytokines such as IL-1β and driving cell lysis. Although GSDMD-mediated pyroptosis has been conventionally understood to be controlled mainly at the post-translational level, through proteolytic cleavage by inflammatory caspases, we have discovered compelling evidence that alternative RNA processing may introduce additional, previously unappreciated complexity in GSDMD regulation. Our laboratories have developed and optimized a highly innovative long-read direct RNA sequencing pipeline, which bypasses conventional cDNA synthesis to avoid artifacts and enables unbiased discovery of native chimeric mRNA (chRNA) in mammalian cells. Using this approach, we have uncovered a remarkably diverse repertoire of chRNA species, including over a thousand unique fusions in murine macrophages and more than two thousand in human inflamed tissues. Among the chRNA found in mice, we identified a chRNA joining the effector domain of GSDMD with a novel C-terminal region encoded by Tmem106a, giving rise to the GSDMD:TMEM106A fusion protein. Functional studies demonstrate that GSDMD:TMEM106A is not only produced in response to inflammatory signals in macrophages but is critical for GSDMD-dependent cytokine release and optimal pyroptosis. Genetic loss of GSDMD:TMEM106A in mice results in reduced cytokine secretion and increased susceptibility to bacterial infection, while in vivo delivery of Gsdmd:Tmem106a mRNA is sufficient for protective immunity. Intriguingly, we have also identified a putative human counterpart, GSDMD:S100A6, which is highly inducible in colon biopsies from patients with inflammatory bowel disease. In this application, we propose a comprehensive exploration of this newly defined class of naturally occurring GSDMD fusion proteins. The specific aims are: (1) to elucidate the subcellular localization, protein-protein interactions, and pore-forming function of GSDMD:TMEM106A during canonical and non-canonical inflammasome activation; (2) to determine the transcriptomic, proteomic, and physiological consequences of GSDMD chRNA expression in vivo during infection, sepsis, and inflammatory disease, and to validate and functionally characterize GSDMD:S100A6 in relevant immune and barrier cell populations. Collectively, this work will establish chimeric splicing as a fundamental source of immunoregulatory protein diversity, redefining the landscape of cell death control in the immune system. By revealing new layers of gasdermin regulation and function, our studies have the potential to identify novel therapeutic strategies for infectious, auto-inflammatory, and immune-mediated diseases.

National Institute of Neurological Disorders and Stroke

Neuroinflammation in Cerebral Small Vessel Disease

May 31, 2031

Project Summary/Abstract Cerebral small vessel disease (cSVD) is a leading cause of vascular contributions to cognitive impairment and dementia (VCID), which is the 2nd leading cause of dementia and a significant contributor to Alzheimer’s disease (AD). Thus far, the underlying pathogenesis of cSVD is poorly understood. Several lines of evidence, including animal models, postmortem human brain pathology, and systemic inflammatory markers, demonstrated the damaging role of chronic neuroinflammation in cSVD. Direct evidence of neuroinflammation at the tissue level in patients with cSVD is still critically needed. The sphingosine-1-phosphate receptor 1 (S1PR1) regulates neuroinflammation through microglial and astrocyte activation and trafficking and has emerged as a promising target for neuroinflammation. In postmortem brains of patients with cSVD, we observed elevated S1PR1 expression and colocalization of S1PR1 with astrocytes and microglia. A novel 11C-CS1P1 PET radiotracer with high affinity and specificity targeting S1PR1 has been recently developed and validated in animal models and post-mortem human specimens. Under an FDA-approved eIND (IND 146548), we have successfully completed the safety and dosimetry study in healthy participants and performed preliminary studies in patients with cSVD. We found that 11C-CS1P1 PET uptake is significantly associated with WMH lesion burden in patients with cSVD after controlling for age, sex, race, vascular risk factors, and amyloid deposition. We hypothesize that 11C-CS1P1 PET uptake is a tissue-level biomarker of neuroinflammation to provide insight into cSVD severity, progression, and prognosis. We will 1) evaluate the relationship between 11C-CS1P1 PET uptake and cSVD neuroimaging abnormalities and cognitive impairment, 2) evaluate the test-retest repeatability and longitudinal evolution, and 3) determine whether 11C-CS1P1 PET uptake at baseline predict cSVD progression. The successful completion of this study will establish 11C-CS1P1 PET as an neuroinflammation imaging biomarker and investigate the role of neuroinflammation in cSVD pathogenesis and progression. It will lay a foundation for developing future therapies in modulating neuroinflammation.

National Institute of Neurological Disorders and Stroke

Linking Single-Cell Transcriptomic, Morphological, and Temporal Signatures of Vulnerability in Neurodegeneration

Mar 31, 2031

Neurodegeneration involves complex cellular phenotypes and molecular changes that vary widely among the cells of the nervous system. Current methodologies permit either detailed molecular profiling (e.g., single-cell transcriptomics) or functional phenotyping (e.g., live imaging of neuronal activity), but not both in the same cells. Thus, it is difficult to directly link a neuron's functional state or fate with its gene expression profile. To address this limitation, we developed an innovative technology, VISTA-FISH (Video Imaging with Spatial- Temporal Analysis by FISH), that couples prospective live-cell imaging with high-resolution spatial transcriptomic profiling of the same cells. This approach enables in situ comparisons of gene expression in neurons that exhibit divergent behaviors or outcomes. Using VISTA-FISH, we will profile iPS-derived human neurons to link single-cell gene expression, morphology, and temporal phenotypes to study molecular pathways driving resilience as well as susceptibility. After exposing neurons carrying TDP43 and C9orf72 mutations to a stimulus inducing TDP43 aggregation, we will jointly record TDP43 localization and neuron activity using live-cell microscopy, then measure single-cell gene expression of the same cells (Aim 1). We will also combine live-cell measurements of TDP43 half-life with CRISPR screening and single-cell gene expression (Aim 2). These rich datasets will enable us to determine transcriptomic changes associated with differences in protein aggregation, protein synthesis, and protein degradation in individual cells, providing an unprecedented molecular perspective on factors responsible for vulnerability and resilience to neurodegeneration.

National Institute of Allergy and Infectious Diseases

Spatial Mapping to Detail the Role of Biomolecules in Governing Biofilm Organization and Resiliency to Stress in Pseudomonas aeruginosa Biofilms

May 31, 2028

PROJECT SUMMARY The bacterium Pseudomonas aeruginosa is a leading cause of hospital acquired infections, exhibiting substantial antibiotic tolerance due to growth in biofilms. Our previous work shows how biofilm fitness is increased by alkyl quinolones (AQs), a class of molecules produced by the Pseudomonas Quinolone Signal (PQS) pathway of Pseudomonas aeruginosa. AQs form aggregates that spatially limit regions of cell death and reduce overall cell death in biofilms. Spatial studies build on ”what” molecules are doing by revealing when, where, and with whom they are found. Others have shown that AQs transiently bind amyloids and our preliminary results find that amyloid localization is shifted in the absence of AQs. However, the spatial relationships of these molecules have not been investigated. Our research combines multiple spatial analytical techniques, such as fluorescence microscopy, polarized light microscopy, confocal Raman microscopy to assemble detailed maps of AQ and amyloid localization during biofilm development. Using transgenic strains we will also determine amyloid distribution as a function of AQ abundance. This work will build on previous findings that AQ concentrations are able to shift locally in response to stress. We hypothesize that this can impact the localization of amyloids and allow biofilms to respond locally to stress, shielding the greater biofilm from damage. We will map biomolecular distribution of entire colony biofilms in response to stress to determine if local responses have the ability to shield more distal regions of the biofilm. The capacity of spatial biomolecular organization to increase bacterial resilience and infection virulence is an understudied area that has the potential to bring to light to novel targets for therapeutics to fight biofilm infections.

National Heart Lung and Blood Institute

Targeting the fibrogenic ECM as an alternative approach to treating IPF

Feb 28, 2028

Project Abstract Idiopathic pulmonary fibrosis and, more broadly, progressive pulmonary fibrosis are wound healing disorders whose hallmark is unorganized and unchecked extracellular matrix (ECM) deposition leading to scarring/stiffening of the lung interstitium. A highly complex, multicellular process, the generation of scar itself is primarily a function of activated fibroblasts with contributions from multiple subpopulations and non-fibroblastic cells. Myofibroblasts, the contractile cohort of activated fibroblasts, physically perturb (i.e. stretch) the local ECM microenvironment, which we have recently shown triggers site-specific, stretch-dependent conformational changes within the ECM protein fibronectin. We have previously demonstrated that a specific stretch-induced conformational change in the critical receptor binding domain of fibronectin triggers a cellular “integrin switch”, a stark change in the ECM receptors used by cells to engage fibronectin. This integrin switch is sufficient to drive activation of naïve lung fibroblasts, acquisition of mesenchymal characteristics in alveolar epithelial cells, and pathogenic remodeling of vascular structures. In this proposal we hypothesize that fibronectin displays a stretch- dependent conformational change specifically in regions of active lung fibrogenesis and that this conformational change disrupts homeostatic integrin binding dynamics in fibroblasts, leading to their acquisition of a pro-fibrogenic phenotype and transcriptional program. We address this hypothesis in a systematic way through three proposed aims. The first aim focuses on quantifying the presence and spatial localization of the stretch-induced conformational change within a cohort of lung fibrosis patient tissue samples, determining if it represents a consistent marker of active fibrogenic regions and elucidation of critical microenvironmental signatures that further expand our understanding of the impact of fibronectin's integrin switch in driving disease. In the second aim we will begin to unravel the molecular mechanism explaining how the integrin switch that emerges because of the stretch-induced conformational change drives fibroblast activation and fibrogenic gene programs using both idealized in vitro culture systems as well as ex vivo human disease tissue models. Finally, in the third aim we will explore the therapeutic potential of binding and blocking this specific stretch-induced conformation of fibronectin using a promising new and potential antibody drug in both in vivo and ex vivo models of disease.

Rob Singer, Florence Besse, Jennifer Lippincott-Schwartz

Human Echolocation for Localization and Navigation – Behaviour and Brain Mechanisms

mRNA transport, trafficking, localization

Einstein Medical College, Institut de Biologie Valrose, Janelia Farm Research Campus

Nov 29, 2023

In the second of this year’s Brain Prize webinars, Rob Singer (Einstein Medical College, USA), Florence Besse (Institut de Biologie Valrose, France) and Jennifer Lippincott-Schwartz (Janelia Farm Research Campus, USA) will present their work on mRNA transport, trafficking, and localization. Each speaker will present for 25 minutes, and the webinar will conclude with an open discussion. The webinar will be moderated by the winners of the 2023 Brain Prize, Michael Greenberg, Erin Schuman and Christine Holt.

Broad Institute, Cambridge, USA

Spatial and Single Cell Genomics for Next Generation Neuroscience

Evan Macosko

Oct 12, 2023

The advent of next generation sequencing ushered in a ten-year period of exuberant technology development, enabling the quantification of gene expression and epigenetic features within individual cells, and within intact tissue sections. In this seminar, I will outline our technological contributions, beginning with the development of Drop-seq, a method for high-throughput single cell analysis, followed by the development of Slide-seq, a technique for measuring genome-wide expression at 10 micron spatial resolution. Using a combination of these techniques, we recently constructed a comprehensive cell type atlas of the adult mouse brain, positioning cell types within individual brain structures. I will discuss the major findings from this dataset, including emerging principles of neurotransmission, and the localization of disease gene signatures to specific cell types. Finally, I will introduce a new spatial technology, Slide-tags, that unifies single cell and spatial genomics into a single, highly scalable assay.

Microbial modulation of zebrafish behavior and brain development

Judith S. Eisen

University of Oregon

May 16, 2023

There is growing recognition that host-associated microbiotas modulate intrinsic neurodevelopmental programs including those underlying human social behavior. Despite this awareness, the fundamental processes are generally not understood. We discovered that the zebrafish microbiota is necessary for normal social behavior. By examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of key forebrain neurons within the social behavior circuitry. The microbiota is also necessary for both localization and molecular functions of forebrain microglia, brain-resident phagocytes that remodel neuronal arbors. In particular, the microbiota promotes expression of complement signaling pathway components important for synapse remodeling. Our work provides evidence that the microbiota modulates zebrafish social behavior by stimulating microglial remodeling of forebrain circuits during early neurodevelopment and suggests molecular pathways for therapeutic interventions during atypical neurodevelopment.

Driving human visual cortex, visually and electrically

Dora Hermes Miller

Mayo Clinic, USA

Nov 16, 2022

The development of circuit-based therapeutics to treat neurological and neuropsychiatric diseases require detailed localization and understanding of electrophysiological signals in the human brain. Electrodes can record and stimulate circuits in many ways, and we often rely on non-invasive imaging methods to predict the location to implant electrodes. However, electrophysiological and imaging signals measure the underlying tissue in a fundamentally different manner. To integrate multimodal data and benefit from these complementary measurements, I will describe an approach that considers how different measurements integrate signals across the underlying tissue. I will show how this approach helps relate fMRI and intracranial EEG measurements and provides new insights into how electrical stimulation influences human brain networks.

Training Dynamic Spiking Neural Network via Forward Propagation Through Time

B. Yin

CWI

Nov 10, 2022

With recent advances in learning algorithms, recurrent networks of spiking neurons are achieving performance competitive with standard recurrent neural networks. Still, these learning algorithms are limited to small networks of simple spiking neurons and modest-length temporal sequences, as they impose high memory requirements, have difficulty training complex neuron models, and are incompatible with online learning.Taking inspiration from the concept of Liquid Time-Constant (LTCs), we introduce a novel class of spiking neurons, the Liquid Time-Constant Spiking Neuron (LTC-SN), resulting in functionality similar to the gating operation in LSTMs. We integrate these neurons in SNNs that are trained with FPTT and demonstrate that thus trained LTC-SNNs outperform various SNNs trained with BPTT on long sequences while enabling online learning and drastically reducing memory complexity. We show this for several classical benchmarks that can easily be varied in sequence length, like the Add Task and the DVS-gesture benchmark. We also show how FPTT-trained LTC-SNNs can be applied to large convolutional SNNs, where we demonstrate novel state-of-the-art for online learning in SNNs on a number of standard benchmarks (S-MNIST, R-MNIST, DVS-GESTURE) and also show that large feedforward SNNs can be trained successfully in an online manner to near (Fashion-MNIST, DVS-CIFAR10) or exceeding (PS-MNIST, R-MNIST) state-of-the-art performance as obtained with offline BPTT. Finally, the training and memory efficiency of FPTT enables us to directly train SNNs in an end-to-end manner at network sizes and complexity that was previously infeasible: we demonstrate this by training in an end-to-end fashion the first deep and performant spiking neural network for object localization and recognition. Taken together, we out contribution enable for the first time training large-scale complex spiking neural network architectures online and on long temporal sequences.

Salk Institute for Biological Studies

Inter-tissue signals modify food-seeking behavior in C. elegans

Sreekanth Chalasani

Oct 11, 2022

Animals modify their behavioral outputs in response to changes in external and internal environments. We use the nematode, C. elegans to probe the pathways linking changes in internal states like hunger with behavior. We find that acute food deprivation alters the localization of two transcription factors, likely releasing an insulin-like peptide from the intestine, which in turn modifies chemosensory neurons and alters behavior. These results present a model for how inter-tissue signals to generate flexible behaviors via gut-brain signaling.

Max Planck Institute for Brain Research, Germany

Translation at the Synapse

Erin Schuman

Jun 1, 2022

The complex morphology of neurons, with synapses located hundreds of microns from the cell body, necessitates the localization of important cell biological machines, including ribosomes, within dendrites and axons. Local translation of mRNAs is important for the function and plasticity of synapses. Using advanced sequencing and imaging techniques we have updated our understanding of the local transcriptome and identified the local translatome- identifying over 800 transcripts for which local translation is the dominant source of protein. In addition, we have explored the unique mechanisms neurons use to meet protein demands at synapses, identifying surprising features of neuronal and synaptic protein synthesis.

National Taiwan University

The function and localization of human consciousness

Po-Jang Brown Hsieh

May 28, 2022

Scientific studies of consciousness can be roughly categorized into two directions: (1) How/where does consciousness emerge? (the mechanism of consciousness) and (2) Why is there consciousness? (the function of consciousness). I will summarize my past research on the quest for consciousness in these two directions.

VA Puget Sound Health Care System, University of Washignton, Seattle, WA, USA

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

Jeffrey Iliff

Oct 25, 2021

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.

Demystifying the richness of visual perception

Ruth Rosenholtz

MIT

Oct 20, 2021

Human vision is full of puzzles. Observers can grasp the essence of a scene in an instant, yet when probed for details they are at a loss. People have trouble finding their keys, yet they may be quite visible once found. How does one explain this combination of marvelous successes with quirky failures? I will describe our attempts to develop a unifying theory that brings a satisfying order to multiple phenomena. One key is to understand peripheral vision. A visual system cannot process everything with full fidelity, and therefore must lose some information. Peripheral vision must condense a mass of information into a succinct representation that nonetheless carries the information needed for vision at a glance. We have proposed that the visual system deals with limited capacity in part by representing its input in terms of a rich set of local image statistics, where the local regions grow — and the representation becomes less precise — with distance from fixation. This scheme trades off computation of sophisticated image features at the expense of spatial localization of those features. What are the implications of such an encoding scheme? Critical to our understanding has been the use of methodologies for visualizing the equivalence classes of the model. These visualizations allow one to quickly see that many of the puzzles of human vision may arise from a single encoding mechanism. They have suggested new experiments and predicted unexpected phenomena. Furthermore, visualization of the equivalence classes has facilitated the generation of testable model predictions, allowing us to study the effects of this relatively low-level encoding on a wide range of higher-level tasks. Peripheral vision helps explain many of the puzzles of vision, but some remain. By examining the phenomena that cannot be explained by peripheral vision, we gain insight into the nature of additional capacity limits in vision. In particular, I will suggest that decision processes face general-purpose limits on the complexity of the tasks they can perform at a given time.

Electrophysiologic Monitoring and Modulation of Enteric Nervous System

Todd Coleman

Stanford University

Aug 13, 2021

We will highlight recent technological and methodological advances in deploying miniaturized technologies that can monitor the spatial electrophysiologic patterns of the visceral nervous system. As an example, we will discuss recent developments of thin, stretchable, wireless biosensor patches that can be embedded within routinely used medical adhesives for recording electrophysiologic patterns of the GI tract. We will also showcase recent developments in array signal processing that enable non-invasive tracking, and source localization, of the slow wave patterns associated with the GI tract. We will illustrate how such systems can also be used in tandem with novel miniaturized pacing devices to can enable closed-loop neuromodulation of the enteric nervous system. We will conclude with a summary of the knowns and unknowns in how multi-organ physiology research, technology miniaturization, and data science may create unique opportunities for the intersection of electrical engineering and neuroscience.

University of Aberdeen, UK

What is serially-dependent perception good for?

Mauro Manassi

Jan 14, 2021

Perception can be strongly serially-dependent (i.e. biased toward previously seen stimuli). Recently, serial dependencies in perception were proposed as a mechanism for perceptual stability, increasing the apparent continuity of the complex environments we experience in everyday life. For example, stable scene perception can be actively achieved by the visual system through global serial dependencies, a special kind of serial dependence between summary statistical representations. Serial dependence occurs also between emotional expressions, but it is highly selective for the same identity. Overall, these results further support the notion of serial dependence as a global, highly specialized, and purposeful mechanism. However, serial dependence could also be a deleterious phenomenon in unnatural or unpredictable situations, such as visual search in radiological scans, biasing current judgments toward previous ones even when accurate and unbiased perception is needed. For example, observers make consistent perceptual errors when classifying a tumor- like shape on the current trial, seeing it as more similar to the shape presented on the previous trial. In a separate localization test, observers make consistent errors when reporting the perceived position of an objects on the current trial, mislocalizing it toward the position in the preceding trial. Taken together, these results show two opposite sides of serial dependence; it can be a beneficial mechanism which promotes perceptual stability, but at the same time a deleterious mechanism which impairs our percept when fine recognition is needed.

Exploring fine detail: The interplay of attention, oculomotor behavior and visual perception in the fovea

Martina Poletti

University of Rochester

Dec 9, 2020

Outside the foveola, visual acuity and other visual functions gradually deteriorate with increasing eccentricity. Humans compensate for these limitations by relying on a tight link between perception and action; rapid gaze shifts (saccades) occur 2-3 times every second, separating brief “fixation” intervals in which visual information is acquired and processed. During fixation, however, the eye is not immobile. Small eye movements incessantly shift the image on the retina even when the attended stimulus is already foveated, suggesting a much deeper coupling between visual functions and oculomotor activity. Thanks to a combination of techniques allowing for high-resolution recordings of eye position, retinal stabilization, and accurate gaze localization, we examined how attention and eye movements are controlled at this scale. We have shown that during fixation, visual exploration of fine spatial detail unfolds following visuomotor strategies similar to those occurring at a larger scale. This behavior compensates for non-homogenous visual capabilities within the foveola and is finely controlled by attention, which facilitates processing at selected foveal locations. Ultimately, the limits of high acuity vision are greatly influenced by the spatiotemporal modulations introduced by fixational eye movements. These findings reveal that, contrary to common intuition, placing a stimulus within the foveola is necessary but not sufficient for high visual acuity; fine spatial vision is the outcome of an orchestrated synergy of motor, cognitive, and attentional factors.

Novel Tools for Spatial and Temporal Genomics

Fei Chen

Broad Institute

Nov 23, 2020

The precise spatial localization of molecular signals within tissues richly informs the mechanisms of tissue formation and function. Here, we’ll introduce Slide-seq, a technology which enables transcriptome-wide measurements with near-single cell spatial resolution. We’ll describe recent experimental and computational advances to enable Slide-seq in biological contexts in biological contexts where high detection sensitivity is important. More broadly, we’ll discuss the promise and challenges of spatial transcriptomics for tissue genomics. Lastly, we’ll touch upon novel molecular recording technologies, which allows recording of the absolute time dynamics of gene expression in live systems into DNA sequences.

Max Planck Institute for Brain Research

Protein Synthesis at Neuronal Synapses

Erin Schuman

Oct 27, 2020

The complex morphology of neurons, with synapses located 100’s of microns from the cell body, necessitates the localization of important cell biological machines and processes within dendrites and axons. Using expansion microscopy together with metabolic labeling we have discovered that both postsynaptic spines and presynaptic terminals exhibit rapid translation, which exhibits differential sensitivity to different neurotransmitters and neuromodulators. In addition, we have explored the unique mechanisms neurons use to meet protein demands at synapses, identifying the transcriptome and translatome in the neuropil.

Multiple maps for navigation

Lisa Giocomo

Stanford University

Oct 22, 2020

Over the last several decades, the tractable response properties of parahippocampal neurons have provided a new access key to understanding the cognitive process of self-localization: the ability to know where you are currently located in space. Defined by functionally discrete response properties, neurons in the medial entorhinal cortex and hippocampus are proposed to provide the basis for an internal neural map of space, which enables animals to perform path-integration based spatial navigation and supports the formation of spatial memories. My lab focuses on understanding the mechanisms that generate this neural map of space and how this map is used to support behavior. In this talk, I’ll discuss how learning and experience shapes our internal neural maps of space to guide behavior.