Identifying neurotransmitter spill-over in hippocampal field recordings.
A model of synaptic and extra-synaptic excitatory signaling in the hippocampus is presented. The model is used to analytically evaluate the potential contributions of homosynaptic and heterosynaptic glutamate spill-over to receptor signaling during an electrophysiological experiment in which glutamate transporters are pharmacologically blocked. Inhibition of glutamate uptake selectively prolongs the decay kinetics of the second field excitatory postsynaptic potential evoked by paired pulse stimulation of Schaffer collateral axons in area CA1. The model includes AMPA and NMDA glutamate receptors, and the removal of glutamate by transporters and diffusion. We establish analytically that the prolongation cannot be caused by local effects, i.e., the transporters acting within or near the synapse. In contrast, a time profile of glutamate consistent with spill-over from adjacent synapses can explain the effect. The different reaction kinetics of AMPA and NMDA receptors have a significant role in reproducing the experimental results, as explained by analysis of the ODEs governing the reactions.
Department of Mathematical Sciences, The University of Montana, Missoula, MT 59812, USA. stone@mso.umt.edu
Emily
E
Stone
Katie
K
Hoffman
Michael
M
Kavanaugh
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D003198:Computer Simulation; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000378:metabolism*; D007700:Kinetics; D008959:Models, Neurological; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate