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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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Fos/FG double labeling after Fluoro-Gold injection into the ventral striatum. A, Schematic figures and digitized photomicrograph showing FG injection site in the ventral striatum and retrograde transportation of FG to label neurons in the ACC. B, Distribution of FG labeled neurons in both sides of ACC with FG injection into the ventral striatum. C-D, Augmented figures showing FG (green) and Fos (red) double-labeling results in rectangle area 1 (C) and 2 (D) in B. Arrowheads on the merged figures indicate FG/Fos double-labeled neurons. Bars equal to 1000 μm in A, 200 μm in B, and 20 μm in C and D.
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Figure 4: Fos/FG double labeling after Fluoro-Gold injection into the ventral striatum. A, Schematic figures and digitized photomicrograph showing FG injection site in the ventral striatum and retrograde transportation of FG to label neurons in the ACC. B, Distribution of FG labeled neurons in both sides of ACC with FG injection into the ventral striatum. C-D, Augmented figures showing FG (green) and Fos (red) double-labeling results in rectangle area 1 (C) and 2 (D) in B. Arrowheads on the merged figures indicate FG/Fos double-labeled neurons. Bars equal to 1000 μm in A, 200 μm in B, and 20 μm in C and D.

Mentions: Confirmation of the projections from the ACC to the SC leads us to wonder if they are related to pain regulation. We then tested the expression of Fos protein, a widely used activity marker [41], in mice exposed to common peroneal nerve (CPN) ligation surgery – a model of neuropathic pain [21]. As expected, significantly more expression of Fos protein was observed in layer V neurons of the ACC in mice with nerve injury as compared with mice receiving sham surgery (Table 1). Among ACC- SC projecting neurons, many of them expressed Fos after nerve injury (mean 71.3 ± 7.3%) (n = 3 mice) (Figure 1C-D) (Table 1). In comparison, we tested the Fos expression in the ACC-ventral striatum (VS) projecting neurons (Figure 4A), which are more likely to be involved in reward function [42]. After FG injection into the VS, FG labeled neurons were observed in the bilateral ACC (Figure 4B). Unlike the corticospinal projecting cells, most of the ACC-VS projecting neurons were found in the ipsilateral ACC (Table 2). FG labeled neurons were distributed mainly in layer V of the dorsal part of the ACC, with scattered neurons in the layers III and VI, but no detectable FG labeled cells in layers I and II. Moreover, Fos staining revealed only small percentage of ACC-VS projection cells were activated after nerve injury (Table 2; Figure 4C-D).


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)

Fos/FG double labeling after Fluoro-Gold injection into the ventral striatum. A, Schematic figures and digitized photomicrograph showing FG injection site in the ventral striatum and retrograde transportation of FG to label neurons in the ACC. B, Distribution of FG labeled neurons in both sides of ACC with FG injection into the ventral striatum. C-D, Augmented figures showing FG (green) and Fos (red) double-labeling results in rectangle area 1 (C) and 2 (D) in B. Arrowheads on the merged figures indicate FG/Fos double-labeled neurons. Bars equal to 1000 μm in A, 200 μm in B, and 20 μm in C and D.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Fos/FG double labeling after Fluoro-Gold injection into the ventral striatum. A, Schematic figures and digitized photomicrograph showing FG injection site in the ventral striatum and retrograde transportation of FG to label neurons in the ACC. B, Distribution of FG labeled neurons in both sides of ACC with FG injection into the ventral striatum. C-D, Augmented figures showing FG (green) and Fos (red) double-labeling results in rectangle area 1 (C) and 2 (D) in B. Arrowheads on the merged figures indicate FG/Fos double-labeled neurons. Bars equal to 1000 μm in A, 200 μm in B, and 20 μm in C and D.
Mentions: Confirmation of the projections from the ACC to the SC leads us to wonder if they are related to pain regulation. We then tested the expression of Fos protein, a widely used activity marker [41], in mice exposed to common peroneal nerve (CPN) ligation surgery – a model of neuropathic pain [21]. As expected, significantly more expression of Fos protein was observed in layer V neurons of the ACC in mice with nerve injury as compared with mice receiving sham surgery (Table 1). Among ACC- SC projecting neurons, many of them expressed Fos after nerve injury (mean 71.3 ± 7.3%) (n = 3 mice) (Figure 1C-D) (Table 1). In comparison, we tested the Fos expression in the ACC-ventral striatum (VS) projecting neurons (Figure 4A), which are more likely to be involved in reward function [42]. After FG injection into the VS, FG labeled neurons were observed in the bilateral ACC (Figure 4B). Unlike the corticospinal projecting cells, most of the ACC-VS projecting neurons were found in the ipsilateral ACC (Table 2). FG labeled neurons were distributed mainly in layer V of the dorsal part of the ACC, with scattered neurons in the layers III and VI, but no detectable FG labeled cells in layers I and II. Moreover, Fos staining revealed only small percentage of ACC-VS projection cells were activated after nerve injury (Table 2; Figure 4C-D).

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