Numbers, Densities, and Colocalization of AMPA- and NMDA-Type Glutamate Receptors at Individual Synapses in the Superficial Spinal Dorsal Horn of Rats

Antal, Miklós; Fukazawa, Yugo; Eördögh, Mária; Muszil, Dóra; Molnár, Elek; Itakura, Makoto; Takahashi, Masami; Shigemoto, Ryuichi

doi:10.1523/jneurosci.1551-08.2008

Cited by 62 publications

(58 citation statements)

References 77 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S3), suggesting that higher NR2B subunit density can suppress synaptic expression of GluR1 subunits. This is in high contrast with uniform AMPA and NMDA distributions in the spinal dorsal horn (23), and may imply the presence in the hippocampus of unique synaptic scaffold proteins associated with these receptors (24,25). In addition to the guidance molecules discussed earlier, investigation of left-right asymmetry in PSD protein expression is necessary for a better understanding of asymmetrical receptor allocation.…”

Section: Discussionmentioning

confidence: 99%

Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Shinohara

Hirase

Watanabe

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

177

193

View full text Add to dashboard Cite

Left-right asymmetry of the brain has been studied mostly through psychological examination and functional imaging in primates, leaving its molecular and synaptic aspects largely unaddressed. Here, we show that hippocampal CA1 pyramidal cell synapses differ in size, shape, and glutamate receptor expression depending on the laterality of presynaptic origin. CA1 synapses receiving neuronal input from the right CA3 pyramidal cells are larger and have more perforated PSD and a GluR1 expression level twice as high as those receiving input from the left CA3. The synaptic density of GluR1 increases as the size of a synapse increases, whereas that of NR2B decreases because of the relatively constant NR2B expression in CA1 regardless of synapse size. Densities of other major glutamate receptor subunits show no correlation with synapse size, thus resulting in higher net expression in synapses having right input. Our study demonstrates universal left-right asymmetry of hippocampal synapses with a fundamental relationship between synaptic area and the expression of glutamate receptor subunits.

show abstract

Section: Discussionmentioning

confidence: 99%

Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Shinohara

Hirase

Watanabe

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

177

193

View full text Add to dashboard Cite

show abstract

“…However, it has yet to be determined whether the present findings can be generalized across other skin and muscle inputs to the SDH, including primary afferents traveling in the saphenous nerve, which is purely cutaneous (Lynn and Carpenter, 1982). Finally, the degree to which the functional differences in glutamatergic signaling between cutaneous and muscle afferents are maintained throughout life remains unclear, as synaptic circuits within the SDH are known to undergo significant reorganization during the early postnatal period (Keller et al, 2001;Baccei et al, 2003;Baccei and Fitzgerald, 2004;Cordero-Erausquin et al, 2005).…”

Section: Discussionmentioning

confidence: 90%

“…The degree to which the mean amplitude of the NMDAR current was inhibited by the bath application of the NR2B-selective NMDAR antagonist Ro 25-6981 maleate (5 M) was measured and compared between the GS and sural inputs. Although the observed NMDAR currents may include activity occurring at "silent" (i.e., pure NMDAR) synapses, which have been documented in the immature spinal dorsal horn (Bardoni et al, 1998;Li and Zhuo, 1998;Baba et al, 2000), the relative contribution of silent synapses to the overall NMDAR currents at sural versus GS afferent synapses was not examined in the present study. The relative expression of Ca 2ϩ -permeable AMPARs at muscle and cutaneous afferent synapses was evaluated by measuring the fraction of monosynaptic EPSC amplitude (averaged from 5 consecutive EPSCs), which was blocked by bath application of the selective Ca 2ϩ -permeable AMPAR antagonist IEM 1460 (10 M).…”

Section: Methodsmentioning

confidence: 86%

“…8) could also mediate the increased susceptibility to synaptic LTP (Hartmann et al, 2004;Youn et al, 2008;Li and Baccei, 2016). This greater relative level of Ca 2ϩ -permeable AMPARs seems unlikely to reflect an absence of the GluR2 subunit at muscle afferent synapses because the vast majority (96%-99%) of postsynaptic sites in the SDH contain GluR2 (Nagy et al, 2004;Antal et al, 2008). However, GluR1 expression varies significantly across postsynaptic sites, even those located in close proximity within an individual dorsal horn neuron (Antal et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…This greater relative level of Ca 2ϩ -permeable AMPARs seems unlikely to reflect an absence of the GluR2 subunit at muscle afferent synapses because the vast majority (96%-99%) of postsynaptic sites in the SDH contain GluR2 (Nagy et al, 2004;Antal et al, 2008). However, GluR1 expression varies significantly across postsynaptic sites, even those located in close proximity within an individual dorsal horn neuron (Antal et al, 2008). Therefore, although both muscle and cutaneous afferent synapses likely contain a mixture of Ca 2ϩ -impermeable and Ca 2ϩ -permeable AMPARs, it remains feasible that a higher ratio of GluR1:GluR2 expression exists at muscle afferent synapses compared with cutaneous inputs.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

Baccei

2017

J. Neurosci.

View full text Add to dashboard Cite

It is well established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared with skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared with pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn neurons process sensory input from muscle versus skin at the synaptic level. Using a novel ex vivo spinal cord preparation, here we identify the functional organization of muscle and cutaneous afferent synapses onto immature rat lamina I spino-parabrachial neurons, which serve as a major source of nociceptive transmission to the brain. Stimulation of the gastrocnemius nerve and sural nerve revealed significant convergence of muscle and cutaneous afferent synaptic input onto individual projection neurons. Muscle afferents displayed a higher probability of glutamate release, although short-term synaptic plasticity was similar between the groups. Importantly, muscle afferent synapses exhibited greater relative expression of Ca 2ϩ -permeable AMPARs compared with cutaneous inputs. In addition, the prevalence and magnitude of spike timing-dependent long-term potentiation were significantly higher at muscle afferent synapses, where it required Ca 2ϩ -permeable AMPAR activation. Collectively, these results provide the first evidence for afferent-specific properties of glutamatergic transmission within the superficial dorsal horn. A larger propensity for activity-dependent strengthening at muscle afferent synapses onto developing spinal projection neurons could contribute to the enhanced ability of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain in children following injury.

show abstract

Spinal plasticity of the nociceptive system

Latrémolière

2016

An Introduction to Pain and Its Relation to Nervous System Disorders

View full text Add to dashboard Cite

Numbers, Densities, and Colocalization of AMPA- and NMDA-Type Glutamate Receptors at Individual Synapses in the Superficial Spinal Dorsal Horn of Rats

Cited by 62 publications

References 77 publications

Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

Spinal plasticity of the nociceptive system

Contact Info

Product

Resources

About