Korean J Physiol Pharmacol Vol 16: 65－70, February, 2012 http://dx.doi.org/10.4196/kjpp.2012.16.1.65 Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long-term Potentiation in the Rat Visual Cortex Sung-W on Park1, Hyun-Jong Jang1, Kwang-Hyun Cho1,2, Myung-Jun Kim1, Shin Hee Yoon1, and Duck-Joo Rhie1,2 1Department of Physiology, College of Medicine, 2Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, Korea Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mecha- nisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3∼ 5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-week- old rats, then declined to the baseline level with aging to 10 weeks. W hereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-HT2 receptors, but not by the activation of either 5-HT1A or 5-HT3 receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats. Key Words: 5-HT, SSRI, Citalopram, 5-HT2 receptor, Para-chloroamphetamine INTRODUCTION Neuromodulators regulate a vast array of brain func- tions. Serotonin (5-hydroxytryptamine, 5-HT), one of the most important neuromodulators, is involved in higher brain functions, such as cognition and emotional states [1]. Also, 5-HT is involved in the induction of long-term syn- aptic plasticity, which is a cellular and molecular mecha- nism of various brain functions such as learning, memory and sensory development [2]. The rat visual cortex receives a huge input of extensively ramified 5-HT fibers from mid- brain raphe nuclei [3]. Since 5-HT has enhanced the in- duction of synaptic long-term potentiation (LTP) and long-term depression (LTD) in the visual cortex of cats [4], 5-HT is proposed as an enabling factor for long-term syn- aptic plasticity [5]. Because LTP and LTD have been pro- posed as a mechanism for ocular dominance plasticity in Received January 16, 2012, Revised February 8, 2012, Accepted February 16, 2012 Corresponding to: Duck-Joo Rhie, Department of Physiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea. (Tel) 82-2-2258-7277, (Fax) 82-2- 532-9575, (E-mail) djrhie@catholic.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 65 the visual cortex [6,7], despite some controversies [8,9], 5-HT appears to be an important neuromodulator involved in ocular dominance plasticity [10]. In contrast to its effect on cats, 5-HT appears to inhibit the induction of LTP and LTD during the critical period in the visual cortex of rats [11-15]. In rats, 5-HT also in- hibits the induction of LTP in various brain regions such as the hippocampus [16], the amygdala [17], and the pre- frontal cortex [18]. Since the 5-HT content in the visual cortex increases during the critical period [11,13], the in- hibitory effect of 5-HT on the induction of LTP in the visual cortex has been suggested as one of molecular mechanisms for the closure of critical period and a decrease in ocular dominance plasticity of rats [11,12]. However, in recent studies, chronic administration of the selective serotonin re- uptake inhibitor (SSRI) fluoxetine has reinstated ocular dominance plasticity and LTP in the visual cortex of adult rats [19,20]. Since the expression patterns of 5-HT receptor subtypes change during postnatal development [4,21], the effect of 5-HT on the induction of LTP and ocular domi- nance plasticity might differ between young and adult rats. However, comprehensive studies on the effect of 5-HT in ABBREVIATIONS: LTP, long-term potentiation; LTD, long-term depression; 5-HT, 5-hydroxytryptamine; SSRI, selective serotonin reuptake inhibitor; TBS, theta-burst stimulation; NMDA, N-methyl- D-aspartate; ACSF, artificial cerebrospinal fluid; BDNF, brain-derived neurotrophic factor; D-AP5, D-aminopentanoate; FP, field potential; GABA, gamma-aminobutyric acid; PCA, para-chloroamphetamine.