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GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.
Neuropsychopharmacology 2017; 42(2):473-484N

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+Show Affiliations

Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.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.Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.Department of Psychology, University of Haifa, Haifa, Israel.Sagol Department of Neurobiology, University of Haifa, Haifa, Israel. The Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel.NMI Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany.Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.NMI Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27634356

Citation

Saha, Rinki, et al. "GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 42, no. 2, 2017, pp. 473-484.
Saha R, Knapp S, Chakraborty D, et al. GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction. Neuropsychopharmacology. 2017;42(2):473-484.
Saha, R., Knapp, S., Chakraborty, D., Horovitz, O., Albrecht, A., Kriebel, M., ... Richter-Levin, G. (2017). GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 42(2), pp. 473-484. doi:10.1038/npp.2016.205.
Saha R, et al. GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction. Neuropsychopharmacology. 2017;42(2):473-484. PubMed PMID: 27634356.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction. AU - Saha,Rinki, AU - Knapp,Stephanie, AU - Chakraborty,Darpan, AU - Horovitz,Omer, AU - Albrecht,Anne, AU - Kriebel,Martin, AU - Kaphzan,Hanoch, AU - Ehrlich,Ingrid, AU - Volkmer,Hansjürgen, AU - Richter-Levin,Gal, Y1 - 2016/09/16/ PY - 2016/04/27/received PY - 2016/08/18/revised PY - 2016/08/22/accepted PY - 2016/10/21/pubmed PY - 2018/1/6/medline PY - 2016/9/17/entrez SP - 473 EP - 484 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 42 IS - 2 N2 - 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. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/27634356/GABAergic_Synapses_at_the_Axon_Initial_Segment_of_Basolateral_Amygdala_Projection_Neurons_Modulate_Fear_Extinction_ L2 - http://dx.doi.org/10.1038/npp.2016.205 DB - PRIME DP - Unbound Medicine ER -