Premium
Plasticity of NMDA receptor‐mediated excitatory postsynaptic currents at perforant path inputs to dendrite‐targeting interneurons
Author(s) -
Harney Sarah C.,
Anwyl Roger
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.234740
Subject(s) - excitatory postsynaptic potential , perforant path , postsynaptic potential , nmda receptor , neuroscience , dendrite (mathematics) , plasticity , nonsynaptic plasticity , synaptic plasticity , chemistry , post tetanic potentiation , biology , biophysics , materials science , inhibitory postsynaptic potential , receptor , metaplasticity , biochemistry , mathematics , geometry , composite material
Key points• NMDA receptors (NMDARs) activated by the neurotransmitter glutamate underlie certain forms of synaptic plasticity in the brain. • These receptors are also subject to plasticity and we have previously described both long‐term potentiation (LTP) and long‐term depression (LTD) of NMDARs in the principal granule cells of the dentate gyrus region of hippocampus. • The functional significance of these changes in NMDARs on hippocampal network activity depends on whether this occurs only on principal, excitatory neurons or if it also occurs on inhibitory interneurons. • Here we demonstrate differences in NMDAR subtype expression and plasticity in dendrite‐targeting interneurons compared to granule cells. • Interneurons displayed LTD of NMDAR‐mediated synaptic transmission in response to perforant path activation and had a high threshold for induction of LTP of NMDAR‐mediated synaptic currents, suggesting that opposing forms of plasticity at inputs to interneurons and principal cells may act to regulate granule cell dendritic integration and processing.Abstract Synaptic plasticity of NMDA receptors (NMDARs) has been recently described in a number of brain regions and we have previously characterised LTP and LTD of glutamatergic NMDA receptor‐mediated EPSCs (NMDAR‐EPSCs) in granule cells of dentate gyrus. The functional significance of NMDAR plasticity at perforant path synapses on hippocampal network activity depends on whether this is a common feature of perforant path synapses on all postsynaptic target cells or if this plasticity occurs only at synapses on principal cells. We recorded NMDAR‐EPSCs at medial perforant path synapses on interneurons in dentate gyrus which had significantly slower decay kinetics compared to those recorded in granule cells. NMDAR pharmacology in interneurons was consistent with expression of both GluN2B‐ and GluN2D‐containing receptors. In contrast to previously described high frequency stimulation‐induced bidirectional plasticity of NMDAR‐EPSCs in granule cells, only LTD of NMDAR‐EPSCs was induced in interneurons in our standard experimental conditions. In interneurons, LTD of NMDAR‐EPSCs was associated with a loss of sensitivity to a GluN2D‐selective antagonist and was inhibited by the actin stabilising agent, jasplakinolide. While LTP of NMDAR‐EPSCs can be readily induced in granule cells, this form of plasticity was only observed in interneurons when extracellular calcium was increased above physiological concentrations during HFS or when PKC was directly activated by phorbol ester, suggesting that opposing forms of plasticity at inputs to interneurons and principal cells may act to regulate granule cell dendritic integration and processing.