Abstract
Recent analysis of genetically modified mice deficient in different kainate receptor (KAR) subunits have strongly pointed to a role of the GluK2 subunit, mediating the vulnerability of the brain towards seizures. Research concerning this issue has focused mainly on the hippocampus. However, several studies point to a potential role of other parts of the hippocampal formation, in particular the entorhinal cortex, in the development of epileptic seizures. There is extensive cell death after such seizures in layer III of the medial entorhinal cortex (LIII mEC), making this region of special interest for investigation into related pathological conditions. We therefore characterized KAR mediated currents in LIII mEC pyramidal neurons by several different approaches. Using patch-clamp technique, in combination with glutamate uncaging in horizontal brain slices, we show that LIII mEC neurons exhibit KAR currents. Use of genetically modified mice reveal that these currents are mediated by GluK2 containing KARs. The IV curve indicates the predominant presence of a Ca2+ impermeable and edited form of the KAR. Finally, we show that GluK2 containing kainate receptors are essential for kainate-induced gamma oscillations within the entorhinal cortex.
Highlights
Kainate receptors (KARs) have a wide functional spectrum, ranging from the presynaptic regulation of transmitter release to the postsynaptic generation of excitatory inward currents [1,2,3]
This study focuses on the layer III of the medial entorhinal cortex, which provides input to the hippocampal CA1 region and subiculum via the perforant path
We show that KAR mediated currents could be evoked in LIII medial entorhinal cortex (mEC) pyramidal neurons
Summary
Kainate receptors (KARs) have a wide functional spectrum, ranging from the presynaptic regulation of transmitter release to the postsynaptic generation of excitatory inward currents [1,2,3]. In contrast to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), which have been studied extensively, the roles and physiological importance of KARs are less well understood, they were originally cloned and described over a decade ago [9,10,11,12] and for reviews see [2,3,13]. One reason for this lack in our understanding of KAR function is the limited availability of pharmacological agents that enable KARs and AMPARs to be functionally distinguished. The recent development of the AMPAR selective antagonists GYKI 52466 and GYKI 53655 has considerably advanced research in the KAR field
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