Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr 5:7:27.
doi: 10.1186/1756-6606-7-27.

No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex

Ming-Gang Liu, Min Zhuo  1
Affiliations

No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex

Ming-Gang Liu et al. Mol Brain. .

Abstract

One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). We found that pharmacological blockade of TRPV1 with either [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide] (AMG9810, 10 μM) or N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791, 20 μM) failed to affect LTP induced by strong theta burst stimulation in the ACC of adult mice. Similarly, neither AMG9810 nor SB366791 blocked the cingulate LTD induced by low-frequency stimulation. Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Pharmacological blockade of TRPV1 activation with AMG9810 does not affect the LTP induction in the ACC. (A and B) An overview of 64-channel multi-electrode array recordings in one AMG9810-treated ACC slice (A: before TBS; B: 2 h after TBS). After stabilizing the baseline responses for 20 min, AMG9810 (10 μM) was bath applied from 20 min before till 20 min after delivery of TBS to the deep layer. It could be apparently seen that AMG9810 infusion could not prevent the LTP induction. Red circles indicate the stimulated channel (Ch. 29). Vertical lines demarcate the different layers in the ACC. (C) Results of one LTP-showing channel (Ch. 38 and Ch. 30) from the superficial layer of one slice for control and AMG9810-treated group, respectively. (D) Summary of averaged data from 5 superficial layer channels of one slice for both control and AMG9810-applied group, respectively. (E) Pooled data of the superficial layer of the ACC from 6 slices from 6 mice. (F) Pooled data in the deep layer of the ACC (n = 5–6 slices/5-6 mice). TBS delivery results in an enduring synaptic potentiation that lasts for at least 2 h, which is not affected by the presence of AMG9810. Insets in (C and F): representative fEPSP traces at time points indicated by the numbers in the graph. Arrows in (C-F) denote the starting point of TBS application. Calibrations in (A, C and F): 100 μV, 10 ms. Error bars in (E and F) represent SEM.
Figure 2
Figure 2
Spatial analysis of LTP distribution in the ACC. (A and B) Polygonal diagrams of the channels that were activated in the baseline (blue, A) and that showed LTP (red, B) in 6 slices from 6 mice. Vertical lines denote the specific layers in the ACC slice. Overlapped blue regions denote frequently activated channels, while overlapped red regions indicate the channels that are most likely to undergo LTP. (C and D) Similar as (A and B) but with TBS delivered in the presence of AMG9810 (n = 6 slices/6 mice). It is evident that the spatial distribution of LTP-showing channels is not altered by the TRPV1 antagonism.
Figure 3
Figure 3
SB366791 cannot block the induction of LTP in the adult mice ACC. (A) Grouped data from 6 slices of 6 mice for SB366791 (20 μM), showing the normal induction of LTP in the superficial layer. (B) Summarized data in the deep layer (n = 6 slices/6 mice). Sample fEPSP recordings taken at the times indicated by the corresponding numbers are shown at the top of each plot. Arrows in (A and B) show the starting point of TBS application. Horizontal bars denote the period of drug delivery. Calibration: 100 μV, 10 ms. Error bars represent SEM. (C and D) Spatial analysis of the effect of SB366791 on LTP distribution in the ACC. Shown are polygonal graphs of the channels that were activated (blue, C) and that exhibited LTP (red, D) when TBS was delivered in the presence of SB366791 (n = 6 slices/6 mice). Vertical lines denote the specific layers in the ACC slice. SB366791 has no effect on the LTP distribution map in the ACC.
Figure 4
Figure 4
Pharmacological blockade of TRPV1 activation with AMG9810 does not affect the LTD induction in the ACC. (A and B) One sample of 64-channel recordings of ACC LTD induction in the presence of AMG9810 (10 μM). A, baseline; B, 1 h after LFS. AMG9810 was bath applied 25 min prior to and during the LFS delivery to the deep layer of the ACC slice. It is clearly illustrated that AMG9810 did not block LFS-induced LTD. Red circles indicate the stimulated channel (Ch. 45). Vertical lines demarcate the different layers in the ACC. (C) Results of one channel (Ch. 46) in the superficial layer of one ACC slice, showing the induction of LTD despite the presence of AMG9810. (D) Summary of averaged data from 6 superficial channels of the same slice. (E) Pooled data for the superficial layer from 6 slices from 6 mice. (F) Pooled data for the superficial layer of the ACC from control group (n = 6 slices/5 mice). (G and H) Summarized data for the deep layer of the ACC from control (H, n = 6 slices/5 mice) and AMG9810-treated (G, n = 6 slices/6 mice) group. Application of AMG9810 did not affect the induction of LTD in any layer of the ACC. Insets in (C, F, G and H): representative fEPSP traces at time points indicated by the numbers in the graph. Horizontal bars in (C-H) denote the period of LFS or drug application as indicated. Calibrations in (A, C, F, G and H): 100 μV, 10 ms. Error bars in (E-H) represent SEM.
Figure 5
Figure 5
Spatial analysis of LTD distribution in the ACC. (A and B) Polygonal diagrams of the channels that were activated in the baseline (blue, A) and that showed LTD (red, B) in 6 slices from 5 mice. Vertical lines denote the specific layers in the ACC slice. Overlapped blue regions denote frequently activated channels, while overlapped red regions indicate the channels that are most likely to undergo LTD. (C and D) Similar as (A and B) but with LFS delivered in the presence of AMG9810 (n = 6 slices/6 mice). It is evident that the spatial distribution of LTD-showing channels is not altered by the TRPV1 antagonism.
Figure 6
Figure 6
SB366791 cannot block the induction of LTD in the adult mice ACC. (A) Grouped data from 6 slices of 6 mice for SB366791 (20 μM), showing the normal induction of LTD in the superficial layer. (B) Summarized data in the deep layer (n = 6 slices/6 mice). Sample fEPSP recordings taken at the times indicated by the corresponding numbers are shown at the top of each plot. Horizontal bars denote the period of LFS or drug application as indicated. Calibration: 100 μV, 10 ms. Error bars represent SEM. (C and D) Spatial analysis of the effect of SB366791 on LTD distribution in the ACC. Shown are polygonal graphs of the channels that were activated (blue, C) and that exhibited LTD (red, D) when LFS was delivered in the presence of SB366791 (n = 6 slices/6 mice). Vertical lines denote the specific layers in the ACC slice. SB366791 has no effect on the LTD distribution map in the ACC.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998;21(3):531–543. doi: 10.1016/S0896-6273(00)80564-4. - DOI - PubMed
    1. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389(6653):816–824. doi: 10.1038/39807. - DOI - PubMed
    1. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–284. doi: 10.1016/j.cell.2009.09.028. - DOI - PMC - PubMed
    1. Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–384. doi: 10.1146/annurev-cellbio-101011-155833. - DOI - PubMed
    1. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288(5464):306–313. doi: 10.1126/science.288.5464.306. - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources