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Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury.

Chen T, Koga K, Descalzi G, Qiu S, Wang J, Zhang LS, Zhang ZJ, He XB, Qin X, Xu FQ, Hu J, Wei F, Huganir RL, Li YQ, Zhuo M - Mol Pain (2014)

Bottom Line: After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced.Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information.Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China. deptanat@fmmu.edu.cn.

ABSTRACT
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.

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Distribution of rabies virus anterograde labeled fibers and terminals in the spinal dorsal horn projected from the ACC. A, The schematic figure showing the design of lentivirus-assistant rabies virus used for anterograde tracing. B-D, After the virus injection into one side of the ACC (B), virus infected fibers and terminals were distributed in the laminae I-III of the spinal cord (c4) (C-D). Rectangled areas of 1–5 in C and D were augmented in E-I respectively. Bars equal to 200 μm in B, 50 μm in C and D, 10 μm in E-I.
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Figure 3: Distribution of rabies virus anterograde labeled fibers and terminals in the spinal dorsal horn projected from the ACC. A, The schematic figure showing the design of lentivirus-assistant rabies virus used for anterograde tracing. B-D, After the virus injection into one side of the ACC (B), virus infected fibers and terminals were distributed in the laminae I-III of the spinal cord (c4) (C-D). Rectangled areas of 1–5 in C and D were augmented in E-I respectively. Bars equal to 200 μm in B, 50 μm in C and D, 10 μm in E-I.

Mentions: Injection of FG may label passing nerve fibers near the injection area. We thus explored anterograde labeling methods to further confirm the direct projections from the ACC to the spinal dorsal horn. We firstly injected phaseolus vulgaris leucoagglutinin (Pha-L), a widely used anterograde neuronal tracer [35,36], into the ACC. Two weeks later, the Pha-L anterograde labeled fibers and terminals were detected in the dorsal layers of the spinal cord, in which most of the varicose and punctate fibers and terminals were distributed in laminae I and II and scattered fibers and terminals were observed in lamina III. No obvious fibers and terminals could be observed in deeper layers (Figure 2). Traditional anterograde tracers, including the Pha-L may have diffusion capacity in injected sites [37], we next used a modified anterograde tracing strategy based on lentivirus-assistant rabies virus system to only stain a small region of the deep ACC and check their projections to the spinal cord. The vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped Lenti-TVA-mKate infected the neurons anterogradely, which located in the ACC and expressed the avian receptor protein (TVA) and mKate restrictlly in the infected neurons (Figure 3) [38]. The rabies virus EnvA-RV-mcherry was a glycoprotein deleted virus and was pseudotyped with the avian sarcoma leucosis virus glycoprotein (EnvA) [39,40]. The EnvA-RV-mcherry could only infect the neurons that express TVA and labeled these Lenti-TVA-mKate infected ACC neurons locally (Figure 3A). We found that one week after the rabies infection in limited group of neurons in the deep layers of ACC (Figure 3B), virus infected varicose fibers and terminals (immunostained with FITC) were detected in the superficial layers (laminae I-III) of the spinal cord. Although the number of virus infected fibers and terminals was significantly less than that of Pha-L labeled ones, their distribution patterns were similar (Figures 2 and 3).


Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury.

Chen T, Koga K, Descalzi G, Qiu S, Wang J, Zhang LS, Zhang ZJ, He XB, Qin X, Xu FQ, Hu J, Wei F, Huganir RL, Li YQ, Zhuo M - Mol Pain (2014)

Distribution of rabies virus anterograde labeled fibers and terminals in the spinal dorsal horn projected from the ACC. A, The schematic figure showing the design of lentivirus-assistant rabies virus used for anterograde tracing. B-D, After the virus injection into one side of the ACC (B), virus infected fibers and terminals were distributed in the laminae I-III of the spinal cord (c4) (C-D). Rectangled areas of 1–5 in C and D were augmented in E-I respectively. Bars equal to 200 μm in B, 50 μm in C and D, 10 μm in E-I.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4060852&req=5

Figure 3: Distribution of rabies virus anterograde labeled fibers and terminals in the spinal dorsal horn projected from the ACC. A, The schematic figure showing the design of lentivirus-assistant rabies virus used for anterograde tracing. B-D, After the virus injection into one side of the ACC (B), virus infected fibers and terminals were distributed in the laminae I-III of the spinal cord (c4) (C-D). Rectangled areas of 1–5 in C and D were augmented in E-I respectively. Bars equal to 200 μm in B, 50 μm in C and D, 10 μm in E-I.
Mentions: Injection of FG may label passing nerve fibers near the injection area. We thus explored anterograde labeling methods to further confirm the direct projections from the ACC to the spinal dorsal horn. We firstly injected phaseolus vulgaris leucoagglutinin (Pha-L), a widely used anterograde neuronal tracer [35,36], into the ACC. Two weeks later, the Pha-L anterograde labeled fibers and terminals were detected in the dorsal layers of the spinal cord, in which most of the varicose and punctate fibers and terminals were distributed in laminae I and II and scattered fibers and terminals were observed in lamina III. No obvious fibers and terminals could be observed in deeper layers (Figure 2). Traditional anterograde tracers, including the Pha-L may have diffusion capacity in injected sites [37], we next used a modified anterograde tracing strategy based on lentivirus-assistant rabies virus system to only stain a small region of the deep ACC and check their projections to the spinal cord. The vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped Lenti-TVA-mKate infected the neurons anterogradely, which located in the ACC and expressed the avian receptor protein (TVA) and mKate restrictlly in the infected neurons (Figure 3) [38]. The rabies virus EnvA-RV-mcherry was a glycoprotein deleted virus and was pseudotyped with the avian sarcoma leucosis virus glycoprotein (EnvA) [39,40]. The EnvA-RV-mcherry could only infect the neurons that express TVA and labeled these Lenti-TVA-mKate infected ACC neurons locally (Figure 3A). We found that one week after the rabies infection in limited group of neurons in the deep layers of ACC (Figure 3B), virus infected varicose fibers and terminals (immunostained with FITC) were detected in the superficial layers (laminae I-III) of the spinal cord. Although the number of virus infected fibers and terminals was significantly less than that of Pha-L labeled ones, their distribution patterns were similar (Figures 2 and 3).

Bottom Line: After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced.Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information.Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China. deptanat@fmmu.edu.cn.

ABSTRACT
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.

Show MeSH
Related in: MedlinePlus