Wu, Y; (2012) Extrasynaptic signalling and plasticity mediated by N-Methyl-D-aspartate receptors. Doctoral thesis , UCL (University College London).

Preview

PDF Yu-Wei PhD thesis_Revised.pdf Available under License : See the attached licence file. Download (5MB)

Abstract

Synaptic N-Methyl-D-aspartate receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs located on the dendritic shaft. Here we find that in CA1 pyramidal neurons backpropagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate of non-vesicular origin. In contrast, spine NMDARs are "protected" under baseline conditions from such glutamate by perisynaptic transporters: bAP-evoked Ca2+ entry through these receptors can be detected upon synaptic glutamate release or local glutamate uncaging. During theta-burst firing, NMDAR-dependent Ca2+ entry either upregulates or downregulates an h-channel conductance (Gh) of the cell depending on whether synaptic glutamate release is intact or blocked. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh-dependent plasticity. These results uncover a novel meta-plasticity mechanism potentially important for neural coding and memory formation.

Download activity - last month

Export as JSONCSVXML

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item