Pathway-specific Differences in Subunit Composition of Synaptic NMDA Receptors on Pyramidal Neurons in Neocortex

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Nov 7

PMID 14602822

Citations 74

Authors

Sanjay S Kumar

John R Huguenard

Affiliations

Soon will be listed here.

Abstract

Heterogeneity of synaptic inputs onto neocortical layer 5 pyramidal neurons could result from differences in the underlying receptors, yet previous work has shown that functional attributes of AMPA receptors are uniform among synaptic connections onto these neurons. To determine whether NMDA receptors (NMDARs) would be similarly uniform, we compared in the same pyramidal neurons pharmacologically isolated NMDAR-mediated EPSCs evoked by stimulation of two anatomically distinguishable pathways, callosal or intracortical. Based on differences in voltage dependence, decay kinetics, apparent Mg2+sensitivity, and subunit-specific (NR2A, NR2B, and NR2C/D) pharmacology, we found NMDARs at these inputs to be distinct. Furthermore, NMDARs activated by the intracortical pathway were more efficient at integrating EPSPs and bringing the neuron closer to the spike-firing threshold than the callosal pathway. These results suggest that pyramidal neurons encode information differentially depending on the origin of their neocortical inputs and that NMDAR-dependent synaptic plasticity may be pathway specific.

Citing Articles

Future Perspectives of NMDAR in CNS Disorders.

Capo T, Rebassa J, Raich I, Lillo J, Badia P, Navarro G Molecules. 2025; 30(4).

PMID: 40005187 PMC: 11857888. DOI: 10.3390/molecules30040877.

NMDA Receptors: Distribution, Role, and Insights into Neuropsychiatric Disorders.

Beaurain M, Salabert A, Payoux P, Gras E, Talmont F Pharmaceuticals (Basel). 2024; 17(10).

PMID: 39458906 PMC: 11509972. DOI: 10.3390/ph17101265.

GluN2C/D-containing NMDA receptors enhance temporal summation and increase sound-evoked and spontaneous firing in the inferior colliculus.

Drotos A, Zarb R, Booth V, Roberts M J Physiol. 2024; .

PMID: 39240253 PMC: 11882938. DOI: 10.1113/JP286754.

Input-specific localization of NMDA receptor GluN2 subunits in thalamocortical neurons.

Topolski M, Gilmore B, Khondaker R, Michniak J, Studtmann C, Chen Y bioRxiv. 2024; .

PMID: 39229083 PMC: 11370540. DOI: 10.1101/2024.08.23.607324.

Functional Dynamics and Selectivity of Two Parallel Corticocortical Pathways from Motor Cortex to Layer 5 Circuits in Somatosensory Cortex.

Kim H, Bonekamp K, Gillie G, Autio D, Keller T, Crandall S eNeuro. 2024; 11(6).

PMID: 38834298 PMC: 11209671. DOI: 10.1523/ENEURO.0154-24.2024.

References

Toth K, McBain C . Afferent-specific innervation of two distinct AMPA receptor subtypes on single hippocampal interneurons. Nat Neurosci. 1999; 1(7):572-8. DOI: 10.1038/2807. View

Tovar K, Westbrook G . The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci. 1999; 19(10):4180-8. PMC: 6782704. View

Gil Z, Connors B, Amitai Y . Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability. Neuron. 1999; 23(2):385-97. DOI: 10.1016/s0896-6273(00)80788-6. View

Tang Y, Shimizu E, Dube G, Rampon C, Kerchner G, Zhuo M . Genetic enhancement of learning and memory in mice. Nature. 1999; 401(6748):63-9. DOI: 10.1038/43432. View

Luscher C, Xia H, Beattie E, Carroll R, von Zastrow M, Malenka R . Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron. 1999; 24(3):649-58. DOI: 10.1016/s0896-6273(00)81119-8. View

Tovar K, Sprouffske K, Westbrook G . Fast NMDA receptor-mediated synaptic currents in neurons from mice lacking the epsilon2 (NR2B) subunit. J Neurophysiol. 2000; 83(1):616-20. DOI: 10.1152/jn.2000.83.1.616. View

Momiyama A . Distinct synaptic and extrasynaptic NMDA receptors identified in dorsal horn neurones of the adult rat spinal cord. J Physiol. 2000; 523 Pt 3:621-8. PMC: 2269820. DOI: 10.1111/j.1469-7793.2000.t01-1-00621.x. View

Misra C, Brickley S, Farrant M, Cull-Candy S . Identification of subunits contributing to synaptic and extrasynaptic NMDA receptors in Golgi cells of the rat cerebellum. J Physiol. 2000; 524 Pt 1:147-62. PMC: 2269854. DOI: 10.1111/j.1469-7793.2000.00147.x. View

Toth K, McBain C . Target-specific expression of pre- and postsynaptic mechanisms. J Physiol. 2000; 525 Pt 1:41-51. PMC: 2269934. DOI: 10.1111/j.1469-7793.2000.00041.x. View

10.

Hrabetova S, Serrano P, Blace N, Tse H, Skifter D, Jane D . Distinct NMDA receptor subpopulations contribute to long-term potentiation and long-term depression induction. J Neurosci. 2000; 20(12):RC81. PMC: 6772441. View

11.

Hausser M, Major G, Stuart G . Differential shunting of EPSPs by action potentials. Science. 2001; 291(5501):138-41. DOI: 10.1126/science.291.5501.138. View

12.

Perez-Otano I, Schulteis C, Contractor A, Lipton S, Trimmer J, Sucher N . Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J Neurosci. 2001; 21(4):1228-37. PMC: 6762235. View

13.

Zhu Y, Auerbach A . K(+) occupancy of the N-methyl-d-aspartate receptor channel probed by Mg(2+) block. J Gen Physiol. 2001; 117(3):287-98. PMC: 2225615. DOI: 10.1085/jgp.117.3.287. View

14.

Barth A, Malenka R . NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses. Nat Neurosci. 2001; 4(3):235-6. DOI: 10.1038/85070. View

15.

Haas K . Directing AMPA receptor traffic. Trends Neurosci. 2001; 24(3):137. DOI: 10.1016/s0166-2236(00)01776-8. View

16.

Brickley S, Farrant M . NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol. 2001; 11(3):327-35. DOI: 10.1016/s0959-4388(00)00215-4. View

17.

Sheng M . Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci U S A. 2001; 98(13):7058-61. PMC: 34622. DOI: 10.1073/pnas.111146298. View

18.

Stern E, Maravall M, Svoboda K . Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo. Neuron. 2001; 31(2):305-15. DOI: 10.1016/s0896-6273(01)00360-9. View

19.

Philpot B, Weisberg M, Ramos M, Sawtell N, Tang Y, Tsien J . Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex. Neuropharmacology. 2001; 41(6):762-70. DOI: 10.1016/s0028-3908(01)00136-8. View

20.

Guo H, Huang L . Alteration in the voltage dependence of NMDA receptor channels in rat dorsal horn neurones following peripheral inflammation. J Physiol. 2001; 537(Pt 1):115-23. PMC: 2278919. DOI: 10.1111/j.1469-7793.2001.0115k.x. View