Project

Back to overview

Mapping the neuronal code of fear

Applicant Gründemann Jan
Number 154765
Funding scheme Ambizione
Research institution Friedrich Miescher Institute for Biomedical Research
Institution of higher education Institute Friedrich Miescher - FMI
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2015 - 31.12.2017
Approved amount 562'146.00
Show all

All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Cellular Biology, Cytology

Keywords (8)

amygdala; fear conditioning; miniature microscopy; in vivo imaging; neuronal plasticity; two-photon microscopy; neuronal circuits; population activity

Lay Summary (German)

Lead
Mapping the neuronal code of fear
Lay summary

Lernen und Gedächtnis bilden die Grundlage unseres täglichen Lebens, sozialer Interaktionen und mentaler Gesundheit. Um die neurophysiologischen Prozesse verstehen zu können, welche zum Bilden und Abrufen von Erinnerungen, aber auch zu Krankheiten, beitragen, ist es essentiell die zu Grunde liegenden neuronalen Schaltkreise zu identifizieren und ihre Funktion zu entschlüsseln. Die neurowissenschaftliche Forschung hat unser Wissen über die zellulären und strukturellen Lernmechanismen beträchtlich erweitert. Dennoch sind viele dieser Erkenntnisse unspezifisch und ihre Relevanz während des Erlernens von Verhaltensmusters nicht verstanden. Weiterhin sind Erinnerungen höchstwahrscheinlich nicht in einzelnen, individuellen Nervenzellen gespeichert. Bisher fehlen uns Erkenntnisse darüber, in welchem Verhältnis die Aktivität einzelner Nervenzellen innerhalb eines Schaltkreises zur Dynamik der restlichen Population steht, wie diese Prozesse zur Codierung von Informationen beitragen und ob sich verschiedene neuronale Schaltkreise darin unterscheiden bzw. wie sie sich während des Lernens verändern. Dazu bedarf es der Aktivitätskartierung von Nervenzellpopulationen aus identifizierten neuronalen Schaltkreisen im sich natürlich verhaltenden Tiermodell. Dieses Projekt hat zum Ziel mithilfe von Gradientenlinsen und kürzlich entwickelten Miniaturmikroskopen, die Populationsaktivität von identifizierten neuronalen Schaltkreisen des Mandelkerns während assoziativen Lernens in freibeweglichen Mäusen zu messen, zu kartieren und zu analysieren. Die erwarteten Ergebnisse werden tiefere Einblicke geben, wie neuronale Schaltkreise Informationen projektionsspezifisch auf zellulärer sowie auf Netzwerkebene speichern und verarbeiten. Auf Grund der besonderen Rolle des Mandelkerns in klinisch relevanten Symptomen, z.B. Angststörungen, hat diese Forschung langfristig gesehen das Potential, mögliche translationale Ansatzpunkte für neuronale schaltkreisspezifische Therapien zu identifizieren.

Direct link to Lay Summary Last update: 26.08.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Amygdala ensembles encode behavioral states.
GründemannJan, BittermanYael, LuTingjia, KrabbeSabine, GreweBenjamin, SchnitzerMark, LüthiAndreas (2019), Amygdala ensembles encode behavioral states., in Science, 364(6437), eaav8736.
Cell-Specific RNA Quantification in Human SN DA Neurons from Heterogeneous Post-mortem Midbrain Samples by UV-Laser Microdissection and RT-qPCR
Duda Johanna, Fauler Michael, Gründemann Jan, Liss Birgit (2018), Cell-Specific RNA Quantification in Human SN DA Neurons from Heterogeneous Post-mortem Midbrain Samples by UV-Laser Microdissection and RT-qPCR, Humana Press, New York City, USA.
Central amygdala circuits modulate food consumption through a positive-valence mechanism
Douglass Amelia M., Kucukdereli Hakan, Ponserre Marion, Markovic Milica, Gruendemann Jan, Strobel Cornelia, Morales Pilar L. Alcala, Conzelmann Karl-Klaus, Luethi Andreas, Klein Ruediger (2017), Central amygdala circuits modulate food consumption through a positive-valence mechanism, in NATURE NEUROSCIENCE, 20(10), 1384-1384.
Neural ensemble dynamics underlying a long-term associative memory
Grewe Benjamin F., Gründemann Jan, Kitch Lacey J., Lecoq Jerome A., Parker Jones G., Marshall Jesse D., Larkin Margaret C., Jercog Pablo E., Grenier Francois, Li Jin Zhong, Luthi Andreas, Schnitzer Mark J. (2017), Neural ensemble dynamics underlying a long-term associative memory, in NATURE, 543(7647), 670-670.
Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval
Xu Chun, Krabbe Sabine, Gründemann Jan, Botta Paolo, Fadok Jonathan P, Osakada Fumitaka, Saur Dieter, Grewe Benjamin F, Schnitzer Mark J, Callaway Edward M, Lüthi A (2016), Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval, in Cell, 167, 961-972.
Projection-Specific Dynamic Regulation of Inhibition in Amygdala Micro-Circuits.
Vogel Elisabeth, Krabbe Sabine, Gründemann Jan, Wamsteeker Cusulin Jacklyn, Lüthi Andreas (2016), Projection-Specific Dynamic Regulation of Inhibition in Amygdala Micro-Circuits., in Neuron, 91(3), 644-651.
Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation
Gründemann Jan, Gründemann Jan, Clark Beverley A. (2015), Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation, in Cell Reports, 12(11), 1715-1722.
Ensemble coding in amygdala circuits for associative learning.
Gründemann Jan (2015), Ensemble coding in amygdala circuits for associative learning., in Current opinion in Neurobiology, 200.
Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning
Krabbe Sabine, Gründemann Jan, Lüthi Andreas, Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning, in Biological Psychiatry, 1.

Collaboration

Group / person Country
Types of collaboration
Prof Mark Schnitzer, Stanford University, USA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
University of Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Annual Meeting of the Society of Neuroscience Talk given at a conference Ensemble coding of amygdala circuits in anxiety and fear behaviours 15.11.2017 Washington, DC, United States of America Gründemann Jan;
Gordon Research Seminar: Amygdala Function in Emotion, Cognition and Disease Talk given at a conference Ensemble coding of amygdala circuits in anxiety and fear behaviours 04.08.2017 Stonehill, United States of America Gründemann Jan;
Movement Disorder Symposium Talk given at a conference Deep brain Ca2+ imaging in freely moving animals 01.09.2016 Luzern, Switzerland Gründemann Jan;
MCN Group Symposium Talk given at a conference Mapping the neuronal code of fear 01.07.2016 Munich, Germany Gründemann Jan;
Cellular and Molecular Neurobiology of Mental Diseases Talk given at a conference Mapping the neuronal code of fear 01.04.2016 Giessbach, Switzerland Gründemann Jan;
Winterneuroscience Conference Talk given at a conference Mapping the neuronal code of fear 01.04.2016 Soelden, Austria Gründemann Jan;
Brain in Focus Meeting Brain Prize Conference Talk given at a conference Mapping the neuronal code of fear 01.04.2016 Copenhagen, Denmark Gründemann Jan;
Cellular and Molecular Neurobiology of Mental Diseases Talk given at a conference Mapping the neuronal code of fear 29.05.2015 Giessbach, Switzerland Gründemann Jan;


Associated projects

Number Title Start Funding scheme
170672 Multisensory integration and associative learning in thalamic circuits 01.01.2018 SNSF Professorships

Abstract

Framework: Learning and memory shape our daily life, social interactions and mental well-being. Deciphering the brain’s neuronal circuits for memory formation and retrieval will be essential to understand the neurophysiological and pathophysiological basis of behavior. Over the last decades, neuroscience research has excelled our knowledge of cellular and structural mechanisms of learning, like long-term potentiation or spine remodeling. Nevertheless, many of these insights are circuit-unspecific from ex vivo studies and their relevance in vivo remains to be tested in naturally behaving animals. In addition, memories are most likely not stored by single nerve cells. We profoundly lack insight into how the activity of individual neurons within a neuronal circuit relates to the dynamics of the rest of the population, to what degree that underlies the encoding of information like stimulus properties or behavioural state and if that relationship is different for distinct neuronal circuits or changes during memory formation. To understand how learning and memory emerge from brain function, neuroscience’s next challenge will be to map large-scale network activity on identified neuronal circuits in naturally behaving animal models. This goal is now closer due to recently developed imaging techniques. Auditory Pavlovian fear conditioning is a well-established associative learning paradigm that highly depends on amygdala function. Here I propose to measure and map population activity as well as structural plasticity of identified neuronal circuits in the amygdala of freely moving, behaving rodents during fear conditioning. To achieve this, I will implement gradient-index lens in vivo imaging in combination with novel ultra-light (2 g) head-mountable miniature microscopes as well as two-photon microscopy. This novel approach will allow me to decipher cellular and network mechanisms of associative fear learning and memory using state of the art imaging techniques in the amygdala of freely moving rodents. Goals: The goal of my Ambizione project is to probe network activity as well as cellular plasticity mechanisms of learning and memory of defined neuronal circuits of the amygdala of freely moving animals in vivo. I will particularly focus on projection-target specific neuronal populations with opposing functions during fear learning and extinction using intersectional viral approaches, genetically encoded Ca2+ indicators, state of the art GRIN-lens imaging in combination with miniature and two-photon microscopy as well as computational neuroscience techniques to address the following two major questions: 1. Population activity of amygdala neurons in fear learning: Are fear learning and extinction encoded in large-scale population dynamics of amygdala principal neurons and can they be mapped onto distinct projection target-specific neuronal circuits.2. Structural plasticity in fear learning: Is fear learning and extinction differentially encoded on a cellular level by dendritic spine remodeling in vivo in a circuit-specific manner. Impact: Using in vivo imaging to map both, population activity as well as the structural dynamics of identified neuronal circuits in the amygdala of freely moving animals will provide fundamental insights into associative fear learning. Moreover, these results will have broader implications into how neuronal circuits store and process information in a projection target-specific manner on a cellular and network level. Addressing fear circuit function in this bottom-up and top-down fashion will be crucial to generate a multi-level theory of how learning and memory emerge in the brain. Given that amygdala dysfunction is strongly linked to clinically-relevant symptoms like anxiety disorders, this research will provide potential translational entry points for neuronal circuit-specific targeted therapies.
-