Kainate receptors and neuronal network connectivity in hippocampus
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1
University of Helsinki, Department of Veterinary Bioscience, Finland
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2
Neuroscience Center, University of Helsinki, Finland
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3
University of Helsinki, Department of Biosciences, Finland
Background: Neonatal hippocampus in rodents displays synchronous activities, which are known to be essential for the maturation of neuronal network. Kainate type glutamatergic receptors (KARs) modulate synaptic transmission and neuronal excitability depending on their subunit composition and localization. The expression of different KAR subunits changes through the development and it is suggested that these receptors facilitate activity dependent synchronization of neurons in early hippocampus. With an in vitro rat hippocampal model and multichannel recordings, we studied the role of KAR subunit GluK1 in neuronal activity development and network synchrony during early development.
Materials and methods: Hippocampal slices were extracted from neonatal rats (P6) and cultured on MED64 Multielectrode array probes (MED-P515A: 8x8 electrodes; electrode size 50 x 50 μm; array size 1×1 mm; spacing 150 μm). Gene expression in CA3 pyramidal neurons was modified with injection of lentiviruses, either carrying a control or GluK1c over-expressing construct. Recordings were acquired by MED system. The spatial and temporal profile of recorded activity was analysed using Spike 2 (CED) and Matlab scripts.
Results: Cultured organotypic rat hippocampi with injections of control viruses spontaneously presented alternating hypersynchronous patterns and latent periods after 10 days in culture (DIV10). GluK1c over-expression in CA3 pyramidal neurons did not alter hypersynchronous patterns neither in duration nor in spike frequency. However, latent periods were significantly shorter in GluK1c over-expressing networks. Hypersynchronous patterns were preceded by short periodic population bursts (duration <100 ms, average incidence around one per second). The incidence of periodic bursts increased before hypersynchronous patterns in control slices. Networks with GluK1c over-expression presented fewer periodic bursts and the increasing incidence was not observed.
The periodic bursts in latent periods originated and spread over the whole hippocampal network at DIV10 in a recurrent fashion, which was associated with depolarization from CA1 stratum radiatum propagating to the CA1-CA3 pyramidal cell layer. In GluK1c over-expressing networks, the origin of depolarization was similar, but the propagation was observed only to CA3 pyramidal layer. Cross correlation analyses from the periodic burst waveforms revealed that in control slices, coefficients were positive throughout the pyramidal layer and negative in the dendritic layer. With GluK1c over-expression, correlations had more centred positive foci in CA3 pyramidal layer with widely spreading negative coefficients in stratum radiatum.
Conclusions: Multichannel recordings were used to study the spatio-temporal profile of network activity in cultured hippocampal slices from newborn rats. In our study, the synchrony of neonatal hippocampal network was altered by local modulation of glutamatergic kainate receptor expression, supporting the notion that kainate receptors might play essential role in the functional integration of neurons in developmental hippocampal circuitries.
References
Lauri SE and Taira T. Kainate receptors in developing presynaptic terminals. WIREs Membr Transp Signal, 2012
Huupponen J, Molchanova S, Lauri SE, Taira T. Ongoing Intrinsic Synchronous Activity is Required for the Functional Maturation of CA3-CA1 Glutamatergic Synapses. Cerebral Cortex. 2013
Vesikansa A, Sakha P, Kuja-Panula J, Molchanova S, Rivera C, Huttunen HJ, Rauvala H, Taira T, Lauri SE. Expression of GluK1c underlies the developmental switch in presynaptic kainate receptor function. Sci. Rep. 2012.
Vesikansa A, Sallert M, Taira T, Lauri SE. Activation of kainate receptors controls the number of functional glutamatergic synapses in the area CA1 of rat hippocampus. J. Physiol. 2007
Sakha P, Vesikansa A, Orav E, Heikkinen J, Kukko-Lukjanov TK, Shintyapina A, Franssila S, Jokinen V, Huttunen HJ, Lauri SE. Axonal Kainate Receptors Modulate the Strength of Efferent Connectivity by Regulating Presynaptic Differentiation. Frontiers in Cellular Neuroscience. 2016
Keywords:
kainate receptor,
organotypic culture,
Hippocampus,
multielectrode array,
network connectivity
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Poster Presentation
Topic:
Neural Networks
Citation:
Kaarela
T,
Chang
W,
Kukko-Lukjanov
T,
Lauri
SE and
Taira
T
(2019). Kainate receptors and neuronal network connectivity in hippocampus.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00079
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Received:
18 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Ms. Tiina Kaarela, University of Helsinki, Department of Veterinary Bioscience, Helsinki, Finland, tiina.kaarela@helsinki.fi