A5000170209- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Memory and Neural Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroendocrine regulation and behavior
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Molecular Communication and Nanonetworks
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Nuclear Receptors and Signaling
- Mesenchymal stem cell research
- Circadian rhythm and melatonin
- CRISPR and Genetic Engineering
- Stress Responses and Cortisol
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- MicroRNA in disease regulation
- Neuroscience of respiration and sleep
- Hypothalamic control of reproductive hormones
- Neurobiology and Insect Physiology Research
- Virus-based gene therapy research
Karolinska Institutet
2016-2025
Massachusetts Institute of Technology
2010-2015
Institute for Learning and Development
2015
McGovern Institute for Brain Research
2010
Broad Institute
2010
Nobel Foundation
2002
Spinal cord injury often results in permanent functional impairment. Neural stem cells present the adult spinal can be expanded vitro and improve recovery when transplanted to injured cord, demonstrating presence of that promote regeneration but normally fail do so efficiently. Using genetic fate mapping, we show close all neural cell potential resides within population ependymal lining central canal. These are recruited by produce not only scar-forming glial cells, also, a lesser degree,...
Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance cognitive tasks. Administration N-methyl-D-aspartate (NMDA) receptor antagonists alters rhythms, and can induce as well psychosis-like symptoms in humans. The disruption NMDA (NMDAR) signaling specifically FS PV is therefore hypothesized to give rise neural network dysfunction could underlie these symptoms. To address the connection between NMDAR...
New neurons are generated from stem cells in a few regions of the adult mammalian brain. Here we provide evidence for generation dopaminergic projection type that lost Parkinson's disease rodent brain and show rate neurogenesis is increased after lesion. The number new under physiological conditions substantia nigra pars compacta was found to be several orders magnitude smaller than granular cell layer dentate gyrus hippocampus. However, if neuronal turnover constant, entire population could...
While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control are largely unknown. Using chronic recordings mice, we found that fast-spiking parvalbumin (FS-PV) interneurons medial prefrontal cortex (mPFC) uniformly show increased sustained firing during goal-driven attentional processing, correlating to level attention. Elevated activity FS-PV neurons on timescale seconds predicted successful execution...
CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report inhibiting generation of progeny by a subclass pericytes led decreased fibrosis and extracellular matrix deposition after spinal cord mice. Regeneration raphespinal corticospinal tract axons was enhanced sensorimotor function recovery improved following animals with attenuated pericyte-derived scarring. Using...
Significance Channelrhodopsins are membrane proteins that enable cellular regulation of transmembrane ion conductance through light-gated pores; these have found application in optogenetics. This paper tests the hypothesis selectivity channelrhodopsins is determined by surface potential pore region: Cations conducted a negatively charged pore, and chloride ions has neutral positively residues. In confirming this applying resulting principles, we engineer improved chloride-conducting channels...
Encoding and predicting aversive events are critical functions of circuits that support survival emotional well-being. Maladaptive circuit changes in valence processing can underlie the pathophysiology affective disorders. The lateral habenula (LHb) has been linked to aversion mood regulation through modulation dopamine serotonin systems. We have defined identity function glutamatergic (Vglut2) control LHb, comparing role inputs originating globus pallidus internal segment (GPi),...
Spinal cord stem cells Injuries to the mammalian spinal do not heal easily. Llorens- Bobadilla et al. studied mouse ependymal cells, which function as for (see Perspective by Becker and Becker). Chromatin accessibility transcriptomic assays revealed that these carry a latent ability differentiate into oligodendrocytes, is much needed remyelination of axons around an injury. The were triggered oligodendrocytes expression oligodendrocyte lineage transcription factor OLIG2. Expression OLIG2 in...
Excitatory projections from the lateral hypothalamic area (LHA) to habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification define structural and functional heterogeneity of LHA-LHb pathway. Our identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles projection patterns. found that genetically defined neurons signal distinct aspects emotional or naturalistic behaviors, such as estrogen...
A central goal of current neuroscience research is to understand how behavior emerges from neuronal circuit activity. For this, cellular and components in intact brains need be identified studied using e.g. viral tracing, electrophysiology, imaging, activity perturbations, behavior. commonality these approaches the establish anatomical locations both experimental parameters (e.g. recording/injection sites) cell bodies/projections). The development standardized coordinate systems, i.e....
The striatal microcircuitry consists of a vast majority projection neurons, the medium spiny neurons (MSNs), and small yet diverse population interneurons. To understand how activity is orchestrated within striatum, it essential to unravel functional connectivity between different neuronal types. Fast-spiking (FS) interneurons provide feedforward inhibition both direct indirect pathway MSNs are important in sculpting their output downstream basal ganglia nuclei. FS also interconnected with...
The underlying circuit imbalance in major depression remains unknown and current therapies remain inadequate for a large group of patients. Discovery the rapid antidepressant effects ketamine - an NMDA receptor (NMDAR) antagonist – has linked glutamatergic system to depression. Interestingly, dysfunction inhibitory GABAergic also been proposed underlie deficits neurons have found with human imaging post-mortem material from depressed Parvalbumin-expressing (PV) interneurons regulate local...
Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband power in the local field potential. Increased baseline also a prominent characteristic schizophrenia and hallmark network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced true rhythm, if so, whether rhythmic involved or not, debated. Asynchronous firing activities are...