In that case, the potentiation induced in the contralateral side would correspond to de-depression of LTD previously induced in vivo with visual simulation. A complementary set of results was obtained when isoproterenol was injected (n = 4 rats) (Figure 8D). In this case pairing with 0mV potentiated synapses only in the ipsilateral hemisphere (p < 0.0001), whereas pairing with −40mV depressed synapses only in the contralateral hemisphere (p < 0.0001). Altogether, the results support the idea that in vivo each agonist facilitate

synaptic changes in one polarity, suppresses changes in the opposite polarity, and do not affect the reversal of plasticity. Temozolomide mw We have shown that agonists for specific Gq11- and Gs-coupled receptors can bring synapses to LTD-only or LTP-only states. To complement these findings we asked whether the polarity of plasticity can also be controlled using antagonists to alter the Gs/Gq11 balance set by endogenous neurotransmitters. We focused on blocking the basal activity of β-adrenergic receptors (coupled AZD8055 to Gs) because we previously showed that blocking LTD induction requires antagonists against multiple Gq11-coupled receptors (adrenergic, serotonergic, cholinergic, and metabotropic glutamate receptors) (Choi et al., 2005). We first examined the effects of the β-antagonist propranolol (5 μM

at least 30 min before baseline and throughout the experiments) on plasticity induced in vitro. At this concentration propranolol did not affect baseline responses (93% ± 4% at 20 min, p = 0.5, n = 5; data not shown) yet it severely impaired the induction of LTP with 0mV pairing (CTR: 141.1 ± 5.1, p < 0.001, n = 20; Prop: 97.5 ± 7.1, p = 0.662, n = 12) (Figure 9A)

and promoted the induction of LTD with −20mV pairing (82.5 ± 8.1, p = 0.068, n = 12; Prop: 76.8 ± 7.7, p = 0.0039. n = 11) (Figure 9B). Next we examined whether systemic administration of propranolol promotes the induction of LTD in vivo using the experimental design described Cell press in Figure 7, which consist of 1 hr of monocular stimulation followed by ex vivo quantification of mEPSCs in the monocular segments of the cortices contra- and ipsilateral to the stimulated eye. In these experiments, we coinjected propranolol (10 mg/kg) with the norepinephrine re-uptake inhibitor maprotiline (10 mg/kg) to boost the endogenous level of norepinephrine. The results, shown in Figure 9C, indicate that the average amplitude of all EPSCs recorded in the contralateral (stimulated) cortices was smaller than the average amplitude of the mEPSCs recorded in the ipsilateral (nonstimulated) cortices (Contra: 13.3 ± 0.39 pA, n = 23 cells; Ipsi: 15.28 ± 0.40 pA, n = 25 cells, five rats; p < 0.0001) (Figure 9C). The distributions of mEPSC amplitude were significantly different (Wilcoxon test: p < 0.0001).