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. Author manuscript; available in PMC: 2016 Nov 18.
Published in final edited form as: Neuron. 2015 Nov 18;88(4):762–773. doi: 10.1016/j.neuron.2015.10.039

Figure 3. M4R regulates dSPN LTD through RGS4 signaling.

Figure 3

(A) LTD was induced with fewer (20) repetitions of the post-pre pairing protocol by co-application of the ACh esterase inhibitor physostigmine (PHY; 10 μM) and VU10010 (VU; 5 μM). The induction was blunted in the presence of the M4R antagonist MT3 (100 nM). Plot of normalized EPSP amplitude as a function of time. The dashed line represents the average of EPSP amplitude before induction. STDP induction is indicated by the vertical bar. (B) Intracellular application of the RGS4 specific inhibitor CCG203769 (CCG; 10 μM) promoted the induction of LTD, even in the absence of the M4R PAM VU10010. The LTD was disrupted by the mGluR5 antagonist MPEP (10 μM). Moreover, (C) CCG enhanced LTD induction even in the presence of M4R antagonist. Solid line (average) and gray shadow (± SEM) are the LTD antagonism by MT3 from the panel (A) for reference. Plot of the average EPSP amplitudes as a function of time. Error bars indicate SEM. (D) Schematic showing the proposed signaling pathway through which M4Rs and D1Rs modulate the induction of dSPN LTD (see also Figure S2).