Axonal Kainate Receptors Modulate the Strength of Efferent Connectivity by Regulating Presynaptic Differentiation

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Sakha , P , Vesikansa , A , Orav , E , Heikkinen , J , Kukko-Lukjanov , T-K , Shintyapina , A , Franssila , S , Jokinen , V , Huttunen , H J & Lauri , S E 2016 , ' Axonal Kainate Receptors Modulate the Strength of Efferent Connectivity by Regulating Presynaptic Differentiation ' , Frontiers in Cellular Neuroscience , vol. 10 , 3 . https://doi.org/10.3389/fncel.2016.00003

Title: Axonal Kainate Receptors Modulate the Strength of Efferent Connectivity by Regulating Presynaptic Differentiation
Author: Sakha, Prasanna; Vesikansa, Aino; Orav, Ester; Heikkinen, Joonas; Kukko-Lukjanov, Tiina-Kaisa; Shintyapina, Alexandra; Franssila, Sami; Jokinen, Ville; Huttunen, Henri J.; Lauri, Sari E.
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Neuroscience Center
University of Helsinki, Biosciences
Date: 2016-01-20
Language: eng
Number of pages: 13
Belongs to series: Frontiers in Cellular Neuroscience
ISSN: 1662-5102
URI: http://hdl.handle.net/10138/182583
Abstract: Kainate type of glutamate receptors (KARs) are highly expressed during early brain development and may influence refinement of the circuitry, via modulating synaptic transmission and plasticity. KARs are also localized to axons, however, their exact roles in regulating presynaptic processes remain controversial. Here, we have used a microfluidic chamber system allowing specific manipulation of KARs in presynaptic neurons to study their functions in synaptic development and function in vitro. Silencing expression of endogenous KARs resulted in lower density of synaptophysin immunopositive puncta in microfluidically isolated axons. Various recombinant KAR subunits and pharmacological compounds were used to dissect the mechanisms behind this effect. The calcium permeable (Q) variants of the low-affinity (GluK1-3) subunits robustly increased synaptophysin puncta in axons in a manner that was dependent on receptor activity and PKA and PKC dependent signaling. Further, an associated increase in the mean active zone length was observed in electron micrographs. Selective presynaptic expression of these subunits resulted in higher success rate of evoked EPSCs consistent with higher probability of glutamate release. In contrast, the calcium-impermeable (R) variant of GluK1 or the high-affinity subunits (GluK4,5) had no effect on synaptic density or transmission efficacy. These data suggest that calcium permeable axonal KARs promote efferent connectivity by increasing the density of functional presynaptic release sites.
Subject: glutamate receptor
kainate receptor
presynaptic
glutamate release probability
microfluidic
synaptogenesis
MOSSY FIBER SYNAPSES
CULTURED HIPPOCAMPAL-NEURONS
SYNAPTIC VESICLES
GROWTH CONE
MATURATION
ACTIVATION
MOTILITY
SYNAPTOGENESIS
PLASTICITY
DYNAMICS
3112 Neurosciences
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