Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA296

Poster Communications

Kainate receptors and neuronal network synchrony in hippocampus

T. Kaarela1,3, W. Chang1, T. Kukko-Lukjanov1, S. Lauri2,3, T. Taira1,3

1. Veterinary Biosciences, University of Helsinki, Helsinki, Finland. 2. Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland. 3. Neuroscience center, University of Helsinki, Helsinki, Finland.

Neonatal hippocampus in rodents displays synchronous activity, which is essential for the maturation of neuronal network. Kainate type glutamate 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. Here we used multichannel recordings to study the role of KAR subunit GluK1 in the spatio-temporal profile of network activity in cultured hippocampal slices from newborn rats. Hippocampal slices were extracted from neonatal rats (P6) and cultured on Multielectrode array probes (MED64; 8x8 50 x 50 μm electrodes). Expression of GluK1 in CA3 pyramidal neurons was modified using lentiviral vectors encoding for EGFP or GluK1c together with EGFP. Recordings were acquired by MED64 system. The spatial and temporal profile of recorded activity was analysed using Spike 2 (CED) and custom made Matlab scripts. Cultured rat hippocampal slices expressing only EGFP (n=11) spontaneously generated hypersynchronous patterns with interleaved latent periods after 10 days in culture (DIV10). GluK1c overexpression (OE) in CA3 pyramidal neurons did not alter the duration or spike frequency of the hypersynchronous patterns. However, latent periods were significantly longer (p<0,05, Student's t-test) in GluK1c OE networks (n=8). Hypersynchronous patterns were preceded by short periodic population bursts (duration<100 ms, average incidence 1/s). The incidence of periodic bursts increased towards the onset of hypersynchronous patterns in control slices. Networks with GluK1c OE presented fewer periodic bursts (p<0,001, Student's t-test) 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, associated with depolarization from CA1 stratum radiatum propagating to the CA1-CA3 pyramidal cell layer. In GluK1c OE networks, the origin of depolarization was similar, but the propagation was observed only to CA3 pyramidal layer. Cross correlation analyses from periodic burst waveforms revealed that in control slices, coefficients were positive throughout CA1-CA3 pyramidal layer and negative in dendritic layer. With GluK1c OE correlations had more centred positive foci in CA3 pyramidal layer with widely spreading negative coefficients in stratum radiatum. In summary, the synchrony of neonatal hippocampal network was altered by local modulation of KAR expression, supporting the notion that these receptors might play essential role in the functional integration of neurons in developmental hippocampal circuitries.

Where applicable, experiments conform with Society ethical requirements