Developmental Switching of Serotonin on LTP 69 did not inhibit the facilitation of LTP by 5-HT application (130.0±5.3% of the baseline FP amplitude, n=11, p＜0.001). The application of the selective 5-HT2C receptor antagonist SB 242084 (5 μM) did not inhibit the facilitation of LTP (135.9±11.4% of the baseline FP amplitude, n=5, p＜0.05). In addition, we tested the effect of another specific 5-HT2C receptor agonist, WAY 161503 (10 μM), which consistently evoked LTP in 8-week-old rats (134.3±10.6% of the baseline FP amplitude, n=8, p＜0.05). These results suggest that the activation of either 5-HT2A or 5-HT2C might be sufficient for the 5-HT facilitation of LTP in adult rats. DISCUSSION Here we showed that, in contrast to the inhibitory effect of 5-HT on the induction of LTP in young rats (3∼5 weeks old), 5-HT facilitated the induction of NMDA receptor-de- pendent LTP in adult rats (8∼10 weeks old). The LTP in adult rats was inhibited by the application of 5-HT2 re- ceptor antagonists and mimicked by the application of 5-HT2 receptor agonists. Our results demonstrate a switch- ing role of 5-HT in the induction of LTP during postnatal development after adolescence in the rat visual cortex. Heightened neuronal plasticity during a certain period of postnatal development as critical period has received much attention because long-term synaptic plasticity is in- volved in sensory cortical development, which is shaped by sensory experience [6,29]. Because the critical period is a very complex phenomenon, many mechanisms are sug- gested for its closure during postnatal development. Among them, age-dependent decline in the induction of long-term synaptic plasticity [7] and late maturation of inhibitory cir- cuits [30,31] have been extensively studied. In the present study, layer-2/3 LTP evoked by the stimulation of layer 4 declined to the baseline level at the ages of 8 and 10 weeks. However, it is known that layer-2/3 LTP evoked by the stimulation of layer 4 is less affected by age, in contrast to the age-dependent decline of layer 2/3 LTP evoked by the stimulation of white matter [23,32]. However, LTP and LTD decreased during postnatal development in the path- way from layer 4 to layer 2/3 in our previous studies [11,22], which might have been a result of the recruitment of in- hibitory circuits using a short-duration (0.1 ms), high-in- tensity stimulation pulse [22]. In the present study, we used stimulation with a longer-duration (0.2 ms), low-in- tensity stimulation pulse to decrease the inhibitory compo- nents in FP, by which LTP in the pathway from layer 4 to layer 2/3 was induced in 5-week-old rats, consistent with our previous study [22]. In the present study, this LTP also declined to the baseline at 8 weeks of age (Fig. 1). The dis- crepancy might have resulted from the inclusion of large inhibitory components in our experiments, as shown in our previous study [22]. Because the proportion of inhibitory components in the FP was critical in the induction of LTP and LTD, late maturation of intracortical inhibitory circuits might inhibit the induction of LTP in this pathway in aged rats [24]. The induction of LTP and LTD in the visual cortex is modulated by various neuromodulators including acetylcho- line (ACh), norepinephrine (NE) and 5-HT [10,33-36], which convey information on the behavioral state of the animal. These neuromodulators appear to act as enabling factors for long-term synaptic plasticity [36,37] and ocular domi- nance plasticity [5,38,39]. However, in contrast to the con- sistent effect of ACh and NE, 5-HT exhibits a dissimilar effect on the induction of LTP/LTD depending on the spe- cies (cats vs. rats) and the age of animals (young vs. adult). Furthermore, 5-HT facilitates the induction of either LTP or LTD in cat visual cortex depending on the expression of 5-HT2 receptors [4]. Whereas increasing the content of 5-HT in the visual cortex inhibits the induction of LTP and LTD during critical period in rats [11-13], 5-HT facilitates the induction of LTP and reinstates ocular dominance plas- ticity in adult rats [19,20]. In the present study, we found that acute treatment of 5-HT facilitated the induction of NMDA receptor-dependent LTP in slices from adult rats at the ages of 8 and 10 weeks, which contrasted with the 5-HT inhibition in the induction of LTP in young rats. The results of experiments with 5-HT-depleted slices and the increase in endogenous 5-HT by citalopram have consis- tently supported these results. This switching role of 5-HT between young and adult rats might be explained by the expression of 5-HT receptor changes with postnatal devel- opment in the neocortex [4,21]. Levels of expression and localization of 5-HT receptor subtypes are critical in the in- duction of LTP [4] and in modulation of cellular excitability [28,40]. Thus, cellular expression of 5-HT receptor subtypes in excitatory and inhibitory neurons during postnatal devel- opment remains to be studied. In addition, 5-HT exerts a trophic function by increasing BDNF levels in the adult brain [41]. Chronic administra- tion of the SSRI fluoxetine or local infusion of 5-HT restores susceptibility to monocular deprivation in adulthood and increases the expression of BDNF [19,20]. In the present study, we demonstrated that the acute administration of 5-HT also facilitated the induction of LTP. Whereas 5-HT1A receptors were involved in the chronic effect of 5-HT and increased expression of BDNF [20], the acute facilitating effect was mediated by the activation of 5-HT2 receptors in the present study. Phospholipase C is coupled to 5-HT2 receptors, which might increase the intracellular calcium level by the release from IP3-sensitive stores [40,42] and could exert additive effects on the activation of NMDA re- ceptors for LTP induction. In contrast, in young rats, en- hanced GABAAergic synaptic currents by 5-HT2 receptor ac- tivation in layer 2/3 pyramidal neurons might inhibit the induction of LTP [40]. Since balance between excitation and inhibition (E/I) is critical in the induction of long-term syn- aptic plasticity [22,43], serotonergic fine tuning of the E/I balance [25] might also play a critical role in the induction of LTP. ACKNOW LEDGEMENTS The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation, in the program year 2009. REFERENCES 1. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38:1083-1152. 2. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. 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