amygdala; fear conditioning; miniature microscopy; in vivo imaging; neuronal plasticity; two-photon microscopy; neuronal circuits; population activity
GründemannJan, BittermanYael, LuTingjia, KrabbeSabine, GreweBenjamin, SchnitzerMark, LüthiAndreas (2019), Amygdala ensembles encode behavioral states., in Science
, 364(6437), eaav8736.
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.
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.
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.
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.
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.
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.
Gründemann Jan (2015), Ensemble coding in amygdala circuits for associative learning., in Current opinion in Neurobiology
Krabbe Sabine, Gründemann Jan, Lüthi Andreas, Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning, in Biological Psychiatry
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.