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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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GluA1/3 mediated the potentiated input–output responses in ACC-spinal cord projecting neurons. A, Digitized photomicrograph showing one DiI retrogradely labeled neuron after injection into the spinal cord (SC) was whole-cell patched and dual labeled by intracellular injection of Alex-488 (1), and one Alex-488 Dextran retrogradely labeled neuron after injection into the ventral striatum (VS) was patched and dual labeled with Alex-594(2). B, Samples and summarized results showing the I-O curve in ACC-SC projecting neurons in mice with nerve injury has steeper slope, as compared with ACC-SC projecting neurons in mice with sham surgery. Meanwhile, the I-O curve in ACC-VS projecting neurons was not different in mice with or without nerve injury. C, Bath application of NASPM only inhibited the I-O responses of neurons from nerve injury but not sham surgery group. D, Bath application of NASPM only inhibited the I-O responses of ACC-SC projecting neurons from nerve injury but not sham surgery group. E, Bath application of NASPM inhibited the I-O responses of ACC-VS projecting neurons from neither nerve injury nor sham surgery group. F. Nerve injury enhanced the I-O responses of ACC-SC projecting neurons in s831A mice but not in s845A mice. Bar equals to 20 μM in A. *,p < 0.05; ***,p < 0.001.
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Figure 6: GluA1/3 mediated the potentiated input–output responses in ACC-spinal cord projecting neurons. A, Digitized photomicrograph showing one DiI retrogradely labeled neuron after injection into the spinal cord (SC) was whole-cell patched and dual labeled by intracellular injection of Alex-488 (1), and one Alex-488 Dextran retrogradely labeled neuron after injection into the ventral striatum (VS) was patched and dual labeled with Alex-594(2). B, Samples and summarized results showing the I-O curve in ACC-SC projecting neurons in mice with nerve injury has steeper slope, as compared with ACC-SC projecting neurons in mice with sham surgery. Meanwhile, the I-O curve in ACC-VS projecting neurons was not different in mice with or without nerve injury. C, Bath application of NASPM only inhibited the I-O responses of neurons from nerve injury but not sham surgery group. D, Bath application of NASPM only inhibited the I-O responses of ACC-SC projecting neurons from nerve injury but not sham surgery group. E, Bath application of NASPM inhibited the I-O responses of ACC-VS projecting neurons from neither nerve injury nor sham surgery group. F. Nerve injury enhanced the I-O responses of ACC-SC projecting neurons in s831A mice but not in s845A mice. Bar equals to 20 μM in A. *,p < 0.05; ***,p < 0.001.

Mentions: Fos staining works suggest that SC but not VS projecting neurons in the ACC are more likely to be activated after nerve injury. It is important to determine if AMPAR mediated EPSCs are selectively enhanced in ACC-SC projecting neurons. After retrograde labeling ACC projecting cells by DiI (0.25%) or Alexa-488 conjugated Dextran (10%) (Figure 6A), we performed electrophysiological recordings from retrogradely labeled cells that were randomly selected from both sides of the ACC. We found that the I-O curve of AMPAR mediated EPSCs of spinal cord projecting neurons has steeper slope in mice with nerve injury, as compared with SC projecting neurons of mice with sham surgery (sham surgery: n = 6 neurons/5 mice. nerve injury: n = 12 neurons/9 mice; Two-way ANOVA followed with Tukey’s post hoc test, F(1, 80) = 22.461, p < 0.001). Interestingly, nerve injury did not affect the I-O curve in ACC-VS projecting neurons (sham surgery: n = 6 neurons/5 mice. nerve injury: n = 8 neurons/6 mice; Two way ANOVA, F(1, 60) =1.531, p > 0.05) (Figure 6B).


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)

GluA1/3 mediated the potentiated input–output responses in ACC-spinal cord projecting neurons. A, Digitized photomicrograph showing one DiI retrogradely labeled neuron after injection into the spinal cord (SC) was whole-cell patched and dual labeled by intracellular injection of Alex-488 (1), and one Alex-488 Dextran retrogradely labeled neuron after injection into the ventral striatum (VS) was patched and dual labeled with Alex-594(2). B, Samples and summarized results showing the I-O curve in ACC-SC projecting neurons in mice with nerve injury has steeper slope, as compared with ACC-SC projecting neurons in mice with sham surgery. Meanwhile, the I-O curve in ACC-VS projecting neurons was not different in mice with or without nerve injury. C, Bath application of NASPM only inhibited the I-O responses of neurons from nerve injury but not sham surgery group. D, Bath application of NASPM only inhibited the I-O responses of ACC-SC projecting neurons from nerve injury but not sham surgery group. E, Bath application of NASPM inhibited the I-O responses of ACC-VS projecting neurons from neither nerve injury nor sham surgery group. F. Nerve injury enhanced the I-O responses of ACC-SC projecting neurons in s831A mice but not in s845A mice. Bar equals to 20 μM in A. *,p < 0.05; ***,p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: GluA1/3 mediated the potentiated input–output responses in ACC-spinal cord projecting neurons. A, Digitized photomicrograph showing one DiI retrogradely labeled neuron after injection into the spinal cord (SC) was whole-cell patched and dual labeled by intracellular injection of Alex-488 (1), and one Alex-488 Dextran retrogradely labeled neuron after injection into the ventral striatum (VS) was patched and dual labeled with Alex-594(2). B, Samples and summarized results showing the I-O curve in ACC-SC projecting neurons in mice with nerve injury has steeper slope, as compared with ACC-SC projecting neurons in mice with sham surgery. Meanwhile, the I-O curve in ACC-VS projecting neurons was not different in mice with or without nerve injury. C, Bath application of NASPM only inhibited the I-O responses of neurons from nerve injury but not sham surgery group. D, Bath application of NASPM only inhibited the I-O responses of ACC-SC projecting neurons from nerve injury but not sham surgery group. E, Bath application of NASPM inhibited the I-O responses of ACC-VS projecting neurons from neither nerve injury nor sham surgery group. F. Nerve injury enhanced the I-O responses of ACC-SC projecting neurons in s831A mice but not in s845A mice. Bar equals to 20 μM in A. *,p < 0.05; ***,p < 0.001.
Mentions: Fos staining works suggest that SC but not VS projecting neurons in the ACC are more likely to be activated after nerve injury. It is important to determine if AMPAR mediated EPSCs are selectively enhanced in ACC-SC projecting neurons. After retrograde labeling ACC projecting cells by DiI (0.25%) or Alexa-488 conjugated Dextran (10%) (Figure 6A), we performed electrophysiological recordings from retrogradely labeled cells that were randomly selected from both sides of the ACC. We found that the I-O curve of AMPAR mediated EPSCs of spinal cord projecting neurons has steeper slope in mice with nerve injury, as compared with SC projecting neurons of mice with sham surgery (sham surgery: n = 6 neurons/5 mice. nerve injury: n = 12 neurons/9 mice; Two-way ANOVA followed with Tukey’s post hoc test, F(1, 80) = 22.461, p < 0.001). Interestingly, nerve injury did not affect the I-O curve in ACC-VS projecting neurons (sham surgery: n = 6 neurons/5 mice. nerve injury: n = 8 neurons/6 mice; Two way ANOVA, F(1, 60) =1.531, p > 0.05) (Figure 6B).

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