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

Tsvetomira Atanasova, Zoya Kharybina, Tiina Anna Marjatta Kaarela, Johanna Tuulia Huupponen, Natalia Luchkina, Tomi Petteri Taira, Sari Elina Lauri

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
JournalNeurochemical Research
Volume44
Issue number3
Pages (from-to)562–571
Number of pages10
ISSN0364-3190
DOIs
Publication statusPublished - Mar 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3112 Neurosciences
  • AMPA receptor
  • GluA4
  • Synaptic plasticity
  • Firing rate homeostasis
  • AMPA-RECEPTORS
  • FUNCTIONAL MATURATION
  • PHOSPHORYLATION SITE
  • GLUTAMATE RECEPTORS
  • SYNAPTIC EFFICACY
  • NETWORK ACTIVITY
  • SUBUNIT
  • LTP
  • CA1
  • SCHIZOPHRENIA

Cite this

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title = "GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus",
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.",
keywords = "3112 Neurosciences, AMPA receptor, GluA4, Synaptic plasticity, Firing rate homeostasis, AMPA-RECEPTORS, FUNCTIONAL MATURATION, PHOSPHORYLATION SITE, GLUTAMATE RECEPTORS, SYNAPTIC EFFICACY, NETWORK ACTIVITY, SUBUNIT, LTP, CA1, SCHIZOPHRENIA",
author = "Tsvetomira Atanasova and Zoya Kharybina and Kaarela, {Tiina Anna Marjatta} and Huupponen, {Johanna Tuulia} and Natalia Luchkina and Taira, {Tomi Petteri} and Lauri, {Sari Elina}",
year = "2019",
month = "3",
doi = "10.1007/s11064-017-2392-8",
language = "English",
volume = "44",
pages = "562–571",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Plenum Publishing Corp",
number = "3",

}

GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus. / Atanasova, Tsvetomira; Kharybina, Zoya; Kaarela, Tiina Anna Marjatta; Huupponen, Johanna Tuulia; Luchkina, Natalia; Taira, Tomi Petteri; Lauri, Sari Elina.

In: Neurochemical Research, Vol. 44, No. 3, 03.2019, p. 562–571.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus

AU - Atanasova, Tsvetomira

AU - Kharybina, Zoya

AU - Kaarela, Tiina Anna Marjatta

AU - Huupponen, Johanna Tuulia

AU - Luchkina, Natalia

AU - Taira, Tomi Petteri

AU - Lauri, Sari Elina

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - 3112 Neurosciences

KW - AMPA receptor

KW - GluA4

KW - Synaptic plasticity

KW - Firing rate homeostasis

KW - AMPA-RECEPTORS

KW - FUNCTIONAL MATURATION

KW - PHOSPHORYLATION SITE

KW - GLUTAMATE RECEPTORS

KW - SYNAPTIC EFFICACY

KW - NETWORK ACTIVITY

KW - SUBUNIT

KW - LTP

KW - CA1

KW - SCHIZOPHRENIA

U2 - 10.1007/s11064-017-2392-8

DO - 10.1007/s11064-017-2392-8

M3 - Article

VL - 44

SP - 562

EP - 571

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 3

ER -