Postsynaptic mGluR5 promotes evoked AMPAR-mediated synaptic transmission onto neocortical layer 2/3 pyramidal neurons during development.
Both short- and long-term roles for the group I metabotropic glutamate receptor number 5 (mGluR5) have been examined for the regulation of cortical glutamatergic synapses. However, how mGluR5 sculpts neocortical networks during development still remains unclear. Using a single cell deletion strategy, we examined how mGluR5 regulates glutamatergic synaptic pathways in neocortical layer 2/3 (L2/3) during development. Electrophysiological measurements were made in acutely prepared slices to obtain a functional understanding of the effects stemming from loss of mGluR5 in vivo. Loss of postsynaptic mGluR5 results in an increase in the frequency of action potential-independent synaptic events but, paradoxically, results in a decrease in evoked transmission in two separate synaptic pathways providing input to the same pyramidal neurons. Synaptic transmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not N-methyl-d-aspartate (NMDA) receptors, is specifically decreased. In the local L2/3 pathway, the decrease in evoked transmission appears to be largely due to a decrease in cell-to-cell connectivity and not in the strength of individual cell-to-cell connections. This decrease in evoked transmission correlates with a decrease in the total dendritic length in a region of the dendritic arbor that likely receives substantial input from these two pathways, thereby suggesting a morphological correlate to functional alterations. These changes are accompanied by an increase in intrinsic membrane excitability. Our data indicate that total mGluR5 function, incorporating both short- and long-term processes, promotes the strengthening of AMPA receptor-mediated transmission in multiple neocortical pathways.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
Kristofer W
KW
Loerwald
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
Ankur B
AB
Patel
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas.
Kimberly M
KM
Huber
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas Jay.Gibson@UTSouthwestern.edu.
Jay R
JR
Gibson
D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission
C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA
cortex; metabotropic glutamate receptor; synapse