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Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex.

Wu LJ, Steenland HW, Kim SS, Isiegas C, Abel T, Kaang BK, Zhuo M - Mol Pain (2008)

Bottom Line: We found that activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro.Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain.The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. longjun.wu@utoronto.ca

ABSTRACT
Both presynaptic and postsynaptic alterations are associated with plastic changes of brain circuits, such as learning and memory, drug addiction and chronic pain. However, the dissection of the relative contributions of pre- and postsynaptic components to brain functions is difficult. We have previously shown peripheral inflammation caused both presynaptic and postsynaptic changes and calcium-stimulated cyclic AMP (cAMP) pathway in the anterior cingulate cortex (ACC) is critical in the synaptic plasticity and behavioral sensitization to pain. It remains to be elucidated whether presynaptic or postsynaptic modulation by cAMP in the ACC could be sufficient for enhancing inflammatory pain. In order to address this question, we took advantage of a novel transgenic mouse model, heterologously expressing an Aplysia octopamine receptor (Ap oa1). This receptor is G protein-coupled and selectively activates the cAMP pathway. We found that activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro. Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain. The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.

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No difference in neuronal excitability or excitatory neurotransmissions in ACC pyramidal neurons from WT and Ap oa1 mice. (A) Diagram illustrating the experimental design and procedures. Ap oa1 receptor is a Gs-coupled receptor from Aplysia. Transgenic mice expressing Ap oa1 receptors were used for slice electrophysiology and inflammatory pain behaviors. (B) Representative traces and pooled results showing neuronal responses to current injections from -200 pA to 200 pA with 100 pA step for 400 ms. Action potentials were induced in neurons from both WT and transgenic mice. (C) Sample trances and pooled results showing no difference in input-output curve of AMPA receptor-mediated EPSCs between WT and Ap oa1 mice. (D) No difference in I-V curve of AMPA receptor-mediated EPSCs between WT and transgenic mice.
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Figure 1: No difference in neuronal excitability or excitatory neurotransmissions in ACC pyramidal neurons from WT and Ap oa1 mice. (A) Diagram illustrating the experimental design and procedures. Ap oa1 receptor is a Gs-coupled receptor from Aplysia. Transgenic mice expressing Ap oa1 receptors were used for slice electrophysiology and inflammatory pain behaviors. (B) Representative traces and pooled results showing neuronal responses to current injections from -200 pA to 200 pA with 100 pA step for 400 ms. Action potentials were induced in neurons from both WT and transgenic mice. (C) Sample trances and pooled results showing no difference in input-output curve of AMPA receptor-mediated EPSCs between WT and Ap oa1 mice. (D) No difference in I-V curve of AMPA receptor-mediated EPSCs between WT and transgenic mice.

Mentions: To examine whether heterologous expression of Ap oa1 affects neuronal and synaptic properties of ACC neurons, we compared the neuronal excitability and basal synaptic transmissions in wild-type (WT) and transgenic mice. Conventional whole-cell patch clamp recordings were performed in pyramidal neurons from layer II/III of the ACC. Pyramidal neurons in the ACC were selected by their morphology and spike properties [33]. We found that there was no difference in the resting membrane potential of ACC pyramidal neurons between WT (-65.1 ± 2.1 mV, n = 25 neurons/15 mice) and Ap oa1 mice (-64.3 ± 1.8 mV, n = 22 neurons/8 mice). No difference was found in the number of spikes in neurons from wild-type and transgenic mice with current injections of either 100 pA or 200 pA (n = 22 neurons/8–12 mice for each group) (Figure 1A and 1B).


Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex.

Wu LJ, Steenland HW, Kim SS, Isiegas C, Abel T, Kaang BK, Zhuo M - Mol Pain (2008)

No difference in neuronal excitability or excitatory neurotransmissions in ACC pyramidal neurons from WT and Ap oa1 mice. (A) Diagram illustrating the experimental design and procedures. Ap oa1 receptor is a Gs-coupled receptor from Aplysia. Transgenic mice expressing Ap oa1 receptors were used for slice electrophysiology and inflammatory pain behaviors. (B) Representative traces and pooled results showing neuronal responses to current injections from -200 pA to 200 pA with 100 pA step for 400 ms. Action potentials were induced in neurons from both WT and transgenic mice. (C) Sample trances and pooled results showing no difference in input-output curve of AMPA receptor-mediated EPSCs between WT and Ap oa1 mice. (D) No difference in I-V curve of AMPA receptor-mediated EPSCs between WT and transgenic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570662&req=5

Figure 1: No difference in neuronal excitability or excitatory neurotransmissions in ACC pyramidal neurons from WT and Ap oa1 mice. (A) Diagram illustrating the experimental design and procedures. Ap oa1 receptor is a Gs-coupled receptor from Aplysia. Transgenic mice expressing Ap oa1 receptors were used for slice electrophysiology and inflammatory pain behaviors. (B) Representative traces and pooled results showing neuronal responses to current injections from -200 pA to 200 pA with 100 pA step for 400 ms. Action potentials were induced in neurons from both WT and transgenic mice. (C) Sample trances and pooled results showing no difference in input-output curve of AMPA receptor-mediated EPSCs between WT and Ap oa1 mice. (D) No difference in I-V curve of AMPA receptor-mediated EPSCs between WT and transgenic mice.
Mentions: To examine whether heterologous expression of Ap oa1 affects neuronal and synaptic properties of ACC neurons, we compared the neuronal excitability and basal synaptic transmissions in wild-type (WT) and transgenic mice. Conventional whole-cell patch clamp recordings were performed in pyramidal neurons from layer II/III of the ACC. Pyramidal neurons in the ACC were selected by their morphology and spike properties [33]. We found that there was no difference in the resting membrane potential of ACC pyramidal neurons between WT (-65.1 ± 2.1 mV, n = 25 neurons/15 mice) and Ap oa1 mice (-64.3 ± 1.8 mV, n = 22 neurons/8 mice). No difference was found in the number of spikes in neurons from wild-type and transgenic mice with current injections of either 100 pA or 200 pA (n = 22 neurons/8–12 mice for each group) (Figure 1A and 1B).

Bottom Line: We found that activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro.Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain.The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. longjun.wu@utoronto.ca

ABSTRACT
Both presynaptic and postsynaptic alterations are associated with plastic changes of brain circuits, such as learning and memory, drug addiction and chronic pain. However, the dissection of the relative contributions of pre- and postsynaptic components to brain functions is difficult. We have previously shown peripheral inflammation caused both presynaptic and postsynaptic changes and calcium-stimulated cyclic AMP (cAMP) pathway in the anterior cingulate cortex (ACC) is critical in the synaptic plasticity and behavioral sensitization to pain. It remains to be elucidated whether presynaptic or postsynaptic modulation by cAMP in the ACC could be sufficient for enhancing inflammatory pain. In order to address this question, we took advantage of a novel transgenic mouse model, heterologously expressing an Aplysia octopamine receptor (Ap oa1). This receptor is G protein-coupled and selectively activates the cAMP pathway. We found that activation of Ap oa1 by octopamine enhanced glutamatergic synaptic transmission in the ACC by increasing presynaptic glutamate release in vitro. Bilateral microinjection of octopamine into the ACC significantly facilitated behavioral responses to inflammatory pain but not acute pain. The present study provides the first evidence linking enhanced presynaptic glutamate release in the ACC to behavioral sensitization caused by peripheral inflammation.

Show MeSH
Related in: MedlinePlus