The Journal of Neuroscience, May 24, 2006, ():
ERK-Dependent Modulation of Cerebellar Synaptic Plasticity after Chronic 
9-Tetrahydrocannabinol Exposure
J. Neurosci. Tonini et al.
26: 5810
Supplemental data
Files in this Data Supplement:
- supplemental material
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Supplemental Fig. 1. The inhibitory effect of 10 μM CP55,940 was fully antagonized by the application of 10 μM SR141716A in slices from vehicle-treated mice. Left,. Representative time course showing the EPSCs inhibition induced by CP55,940 and the wash out following bath application of SR141716A. Right, Superimposed sample traces of control EPSCs, inhibition by 10 μM CP55,940 and wash out by SR141716A.
- supplemental material
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Supplemental Fig. 2. A, B. A1R activation was required for induction but not maintenance of tetanus-induced LTD (8Hz, 15 s) in THC-tolerant mice. A, B. Averaged time course (n=3, mean ± S.E.M) of tetanus-induced changes in normalized PF EPSC amplitudes. A. The decrease in EPSC amplitude was unchanged when the A1R antagonist DPCPX (500 nM) was bath applied 30 s (■) or 5 min (○) after tetanus, but was prevented when DPCPX was applied before stimulation (Fig. 6C). B. Application of DPCPX (500 nM), 30 min following tetanus did not reverse LTD, indicating that continuous activation of A1R was not required to maintain the EPSC depression.
Traces were acquired every 0.033 Hz. and averaged every 10 s. Tetanus was given at t=10 min (indicated by the arrow). C. Application of 500 nM DPCPX did not alter EPSC amplitude in slices originating from either vehicle- or chronic THC-treated mice.
- supplemental material
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Supplemental Fig. 3. Concentration-response curve for PF-PC EPSCs inhibition in cerebellar slices from RasGRF1 +/+ and -/- mice after chronic vehicle treatment, showing that efficacy, but not potency, of CP55,940 effect was reduced in -/- compared to +/+.
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Supplemental Fig. 4. Proposed mechanism of for A1R-mediated LTD in THC tolerant mice.
A. In vehicle-treated mice, brief tetanic stimulation (8Hz, 15s) induced a presynaptic activation of Ca2+ sensitive adenylyl cyclases, leading to rise in the concentration of cAMP and the consequent activation of PKA, triggering PF-PC LTP (Salin et al., 1996). B. Chronic THC exposure caused a ERK dependent CB1R modifications (downregulation/desensitization) (Rubino et al., 2005), in parallel with an up-regulation of adenylyl cyclase activity. This latter event resulted in adenosine release in the extracellular space after tetanic stimulation and thereby in A1R-mediated inhibition of synaptic release (LTD).
C. In-vivo inhibition of ERK pathway by SL327 pre-treatment prevented chronic THC-induced CB1R plasticity and restored physiological LTP at PF-PC synapses.
