title: GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.
abstract: Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
authors.forename: Rinki
authors.initials: R
authors.lastname: Saha
authors.affiliation: Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.|Graduate School for Neural and Behavioral Science, University of Tübingen, Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Knapp
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
authors.forename: Darpan
authors.identifier: 0000-0002-1087-0443
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Horovitz
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.|The Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel.
authors.forename: Anne
authors.initials: A
authors.lastname: Albrecht
authors.affiliation: NMI Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kriebel
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
authors.forename: Hanoch
authors.initials: H
authors.lastname: Kaphzan
authors.affiliation: Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ehrlich
authors.affiliation: NMI Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany.
authors.forename: Hansjürgen
authors.initials: H
authors.lastname: Volkmer
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.|Department of Psychology, University of Haifa, Haifa, Israel.|The Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Richter-Levin
mesh_terms: D000200:Action Potentials; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001369:Axons / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000166:cytology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D059330:GABAergic Neurons / Q000166:cytology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D017774:Long-Term Potentiation; D008297:Male; D055369:Miniature Postsynaptic Potentials; D009414:Nerve Growth Factors / Q000235:genetics; D009433:Neural Inhibition; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504594:Nfasc protein, rat; D005680:gamma-Aminobutyric Acid