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GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3–CA1 Circuitry in the Hippocampus

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Abstract

During the course of development, molecular mechanisms underlying activity-dependent synaptic plasticity change considerably. At immature CA3–CA1 synapses in the hippocampus, PKA-driven synaptic insertion of GluA4 AMPA receptors is the predominant mechanism for synaptic strengthening. However, the physiological significance of the developmentally restricted GluA4-dependent plasticity mechanisms is poorly understood. Here we have used microelectrode array (MEA) recordings in GluA4 deficient slice cultures to study the role of GluA4 in early development of the hippocampal circuit function. We find that during the first week in culture (DIV2–6) when GluA4 expression is restricted to pyramidal neurons, loss of GluA4 has no effect on the overall excitability of the immature network, but significantly impairs synchronization of the CA3 and CA1 neuronal populations. In the absence of GluA4, the temporal correlation of the population spiking activity between CA3–CA1 neurons was significantly lower as compared to wild-types at DIV6. Our data show that synapse-level defects in transmission and plasticity mechanisms are efficiently compensated for to normalize population firing rate at the immature hippocampal network. However, lack of the plasticity mechanisms typical for the immature synapses may perturb functional coupling between neuronal sub-populations, a defect frequently implicated in the context of developmentally originating neuropsychiatric disorders.

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Funding

The funding was provided by Suomen Akatemia, Sigrid Juséliuksen Säätiö, Jane ja Aatos Erkon Säätiö and CIMO.

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Author notes

  1. Natalia V. Luchkina

    Present address: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA

Authors and Affiliations

  1. Neuroscience Center, University of Helsinki, Helsinki, Finland

    Tsvetomira Atanasova, Zoya Kharybina, Tiina Kaarela, Johanna Huupponen, Natalia V. Luchkina, Tomi Taira & Sari E. Lauri

  2. Department of Biosciences, University of Helsinki, Helsinki, Finland

    Johanna Huupponen & Sari E. Lauri

  3. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland

    Tsvetomira Atanasova, Zoya Kharybina, Tiina Kaarela & Tomi Taira

Authors
  1. Tsvetomira Atanasova
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  2. Zoya Kharybina
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  3. Tiina Kaarela
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  4. Johanna Huupponen
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  5. Natalia V. Luchkina
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  6. Tomi Taira
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  7. Sari E. Lauri
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Correspondence to Sari E. Lauri.

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Atanasova, T., Kharybina, Z., Kaarela, T. et al. GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3–CA1 Circuitry in the Hippocampus. Neurochem Res 44, 562–571 (2019). https://doi.org/10.1007/s11064-017-2392-8

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  • DOI: https://doi.org/10.1007/s11064-017-2392-8

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