Neurophysiology, basic and clinical 1279 LTD induction suppresses LTP-induced hippocampal adult neurogenesis Sung Kun Chun a,b , Woong Sun b and Min Whan Jung a Neurogenesis persists in certain adult brain regions including the dentate gyrus. Recent studies have shown that long-term potentiation (LTP) induction in the afferent pathway enhances adult neurogenesis in the dentate gyrus. Here, we investigated whether long-term depression (LTD) induction also affects adult neurogenesis. We induced LTD in the dentate gyrus in one hemisphere and compared the amount of progenitor proliferation with that in the other hemisphere. Unlike LTP induction, LTD induction per se did not affect progenitor cell proliferation in the dentate gyrus. However, when LTD was induced a day before LTP induction, neuronal progenitor cell proliferation facilitated by LTP induction was markedly blunted. These results show that two forms of synaptic plasticity, LTP and LTD, differentially influence hippocampal adult neurogenesis. NeuroReport 20:1279–1283  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. NeuroReport 2009, 20:1279–1283 Key words: adult neurogenesis, cell proliferation, hippocampus, LTD and LTP, progenitor a Neuroscience Laboratory, Institute for Medical Sciences, Ajou University School of Medicine, Suwon and b Department of Anatomy, BK21 program, Korea University College of Medicine, Seoul, Korea Correspondence to Dr Min Whan Jung, PhD, Neuroscience Laboratory, Institute for Medical Sciences, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon 443-721, Korea Tel: + 82 31 219 4525; fax: + 82 31 219 4530; e-mail: min@ajou.ac.kr Received 15 June 2009 accepted 28 June 2009 Introduction The dentate gyrus is among well-documented adult neurogenic regions where new neurons are continuously added throughout life [1,2]. As continuous addition of new neurons requires concurrent remodeling of neuro- nal connectivity, adult neurogenesis is likely to closely interact with the regulation of neuronal plasticity and related hippocampal functions such as learning and memory. In this regard, we and others have demon- strated that induction of long-term potentiation (LTP) in the perforant path enhances proliferation of stem/ progenitor cells and survival of newly generated neurons in the dentate gyrus [3,4]. While LTP is one form of synaptic plasticity yielding sustained increases in synaptic efficacy, long-term depression (LTD) is another form of synaptic plasticity, yielding sustained decrease in synaptic efficacy [5]. As LTD induction and expression are significantly facilitated under stress and in animal models of depression, it has been proposed that LTD is related to stress and depression [6,7]. It is also well known that stressors decrease hippocampal neurogenesis in rodents and nonhuman primates [8], and chronic antidepressant administration increases neurogenesis in the adult hippocampus, which is necessary for therapeutic action [9]. Collectively, these results raise the possibility that synaptic plasticity related to LTD might also contribute to the regulation of adult neurogenesis, which was addressed in this study. Methods Male Sprague–Dawley rats (approximately 9–11 weeks old, 250–330 g, n = 16) were individually housed and allowed free access to food and water. Stimulating and recording electrodes were implanted bilaterally in the angular bundle and hilus, respectively, under deep anesthesia as described earlier [4]. Stimulation elicited mixed medial and lateral perforant path-evoked poten- tials recorded in the hilar region of the dentate gyrus. One week after surgery, the animals received one of the following four treatments to one hemisphere: (i) LTD- inducing low-frequency stimulation (LFS, 1 Hz, 900 pulses, 0.2 ms stimulus duration) 2 h before bromo-deoxyuridine (BrdU) injection (n =4), (ii) LTP-inducing high-frequency stimulation (HFS, 10 pulses at 400 Hz, repeated 10 times at 0.1 Hz) 2 h before BrdU injection (n =4), (iii) LTD- inducing LFS 1 day before BrdU injection (n = 4), and (iv) LTP-inducing HFS 2h before BrdU injection combined with LTD-inducing LFS 1 day before HFS (n = 4) (see Fig. 1 for a schematic summary of the experimental protocol). In all animals, baseline LFS (100 pulses at 0.05 Hz) was delivered to the other (control) hemisphere immediately after delivering LTP-inducing or LTD-inducing stimulation to the experimental hemi- sphere. They were sacrificed 2 h after BrdU injection (200 mg/kg) for histological processes. This protocol has been used widely to assess the number of proliferating (rather than surviving) cells in the hippocampus [10,11]. Experiments were performed in the dark phase of 12-h light/dark cycle. The experimental protocol was approved by the Ethics Review Committee for Animal Experi- mentation of the Ajou University School of Medicine. The magnitude of LTP (or LTD) was determined by measuring the slope of the initial positive phase of the 0959-4965  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/WNR.0b013e3283303794 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.