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Coactivation of thalamic and cortical pathways induces input timing–dependent plasticity in amygdala

Nature Neuroscience volume 15, pages 113–122 (2012)Cite this article

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Abstract

Long-term synaptic enhancements in cortical and thalamic auditory inputs to the lateral nucleus of the amygdala (LAn) mediate encoding of conditioned fear memory. It is not known, however, whether the convergent auditory conditioned stimulus (CSa) pathways interact with each other to produce changes in their synaptic function. We found that continuous paired stimulation of thalamic and cortical auditory inputs to the LAn with the interstimulus delay approximately mimicking a temporal pattern of their activation in behaving animals during auditory fear conditioning resulted in persistent potentiation of synaptic transmission in the cortico-amygdala pathway in rat brain slices. This form of input timing–dependent plasticity (ITDP) in cortical input depends on inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ release from internal stores and postsynaptic Ca2+ influx through calcium-permeable kainate receptors during its induction. ITDP in the auditory projections to the LAn, determined by characteristics of presynaptic activity patterns, may contribute to the encoding of the complex CSa.

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Figure 1: Paired stimulation of thalamic and cortical inputs induces ITDP at the cortico-LAn synapses.
Figure 2: Dependence of ITDP induction on the time interval between TSt and CSt.
Figure 3: Requirements for the induction of ITDP.
Figure 4: Coactivation of GluR5-containing KARs and group I mGluRs during ITDP induction.
Figure 5: Spatiotemporal summation of KAR-mediated EPSCs during TSt-CSt stimulation.
Figure 6: KARs in dendritic spines of LAn neurons are Ca2+ permeable.
Figure 7: Fractional contribution of the AMPAR-, KAR- and NMDAR-mediated synaptic components to the compound EPSP during the TSt-CSt paired stimulation.
Figure 8: ITDP in cortico-LAn pathway is occluded in slices from fear-conditioned rats.

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Acknowledgements

We thank Y. Li and K. Tully for constructive discussions. This study was supported by US National Institutes of Health grants MH083011, MH090464 (V.Y.B.) and MH079079 (S.S.Z.), the National Alliance for Research on Schizophrenia and Depression (V.Y.B.), Whitehall Foundation (V.Y.B.), and US Army Medical Research Acquisition Activity grant #W81XWH-08-2-0126 (V.Y.B.).

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Authors and Affiliations

  1. Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA

    Jun-Hyeong Cho, Edward G Meloni, Karyn M Myers, William A Carlezon Jr & Vadim Y Bolshakov

  2. Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Ildar T Bayazitov & Stanislav S Zakharenko

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  1. Jun-Hyeong Cho
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Contributions

J.-H.C., I.T.B., E.G.M., K.M.M., W.A.C. and S.S.Z. performed the experiments and analyzed the results. V.Y.B. and J.-H.C. designed the experiments, interpreted the results and wrote the paper.

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Correspondence to Vadim Y Bolshakov.

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Cho, JH., Bayazitov, I., Meloni, E. et al. Coactivation of thalamic and cortical pathways induces input timing–dependent plasticity in amygdala. Nat Neurosci 15, 113–122 (2012). https://doi.org/10.1038/nn.2993

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