LONG-TERM POTENTIATION IN VISUAL CORTICAL PROJECTIONS TO THE MEDIAL PREFRONTAL CORTEX OF THE RAT M. J. KIM, a S.-K. CHUN, a Y. B. KIM, a I. MOOK-JUNG b AND M. W. JUNG a * a Neuroscience Laboratory, Institute for Medical Sciences, Ajou Uni- versity School of Medicine, Suwon 442-721, Korea b Brain Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Korea Abstract—In order to investigate neural mechanisms by which the prefrontal cortex adaptively modifies its activities based on past experience, we examined whether or not sen- sory cortical projections to the medial prefrontal cortex sup- port long-term potentiation (LTP) in rats. Monosynaptic pro- jections from the secondary visual cortex, mediomedial area (V2MM) to the infralimbic cortex were confirmed by ortho- dromic as well as antidromic activation of single units. High- frequency stimulation (50 Hz, 2 s) induced LTP (approximate- ly 45% increase over the baseline) in the V2MM projection to the infralimbic cortex. LTP induction in this pathway was completely blocked by an injection (i.p.) of CPP, an N-methyl- D-aspartate receptor antagonist. LTP was also induced in the ventral hippocampal projection to the infralimbic cortex by the same high-frequency stimulation. The present results suggest that modification of synaptic weights of afferent sensory cortical projections is one mechanism underlying learning-induced changes in prefrontal cortical neural activities. © 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. Key words: LTP, V2MM, ventral hippocampus, infralimbic cortex, NMDA receptor, synaptic plasticity. Modifying behavioral strategies in accordance with changes in environment is extremely important for survival. The prefrontal cortex (PFC) is likely to play a crucial role in this adaptive process considering that one important func- tion of the PFC is the planning of future behaviors (Gold- man-Rakic, 1987; Fuster, 1997). In this regard, one of the well-known deficits following damage in the PFC is inability of an animal to adapt to changes in behavioral tasks (Fus- ter, 1997). Results from single-unit recording studies also indicate that the activities of PFC units are altered by learning (Watanabe, 1990; Maxwell et al., 1994; Asaad et al., 1998; Schoenbaum et al., 1999; Mulder et al., 2000; Rainer and Miller, 2000; Baeg et al., 2001). These studies indicate that learning is an essential component of the PFC functions. The mechanisms of learning-induced changes in PFC activity are currently unclear. The changes in PFC activity may reflect learning-induced alterations in the input structures. On the other hand, considering that long-term synaptic plasticity has been shown in the PFC, it is likely that synaptic plasticity within the PFC plays an important role in this process. In rats, long-term potentiation (LTP) and long-term depression have been demonstrated in PFC slices (Hirsch and Crepel, 1990), hippocampal projections to the PFC (Laroche et al., 1990; Doyere et al., 1993; Mulder et al., 1997; Takita et al., 1999), thalamic projec- tions to the PFC (Herry et al., 1999; Gemmell and O’Mara, 2002), and commissural PFC projections to the contralat- eral PFC (Gemmell and O’Mara, 2000). The PFC is extensively interconnected with cortical areas that are involved in sensory processing. In monkeys, the primary sensory cortices of the visual, somatosensory, and auditory systems do not send direct projections to the PFC. Instead, they first project to adjacent sensory associational areas. In parallel with sequential projections to higher-order sensory-association areas, each area in the sequence projects to discrete regions of the PFC (Pandya and Yeterian, 1990; Barbas, 1992; Fuster, 1997). The PFC of the rat is also extensively connected with sensory-association areas for these modalities (Conde et al., 1995). Regarding smell and taste, the primary olfactory and gustatory cortices send direct projections to the PFC (Rolls, 1989; Barbas, 1993; Car- michael et al., 1994; Conde et al., 1995). Thus, external sensory information is richly provided to the PFC from pri- mary or associational sensory cortices. Although synaptic plasticity has been reported in various projection systems in the PFC (see above), it is currently unknown whether or not sensory cortical projections to the PFC support synaptic weight changes. Synaptic plasticity in these pathways would provide the PFC with the flexibility of encoding specific sen- sory inputs and adaptively modifying its activities in response to previously meaningful stimuli. In this study, LTP induction was examined in the projec- tion from the secondary visual cortex, mediomedial area (V2MM) (Paxinos and Watson, 1998) to the infralimbic cortex (ILC), which was previously shown by a retrograde tracing study (Conde et al., 1995), in adult rats. Parts of the results have been reported in abstract form (Kim and Jung, 1999). EXPERIMENTAL PROCEDURES Subjects Experiments were performed with male Sprague–Dawley rats (approximately 9 –11 weeks old, 250 –330 g, n=49). Animals were *Corresponding author. Tel: +82-31-219-4525; fax: +82-31-219- 4503. E-mail address: min@ajou.ac.kr (M. W. Jung). Abbreviations: CPP, 4-(3-phosphonopropyl)-2-piperazine-carboxylic acid; ILC, infralimbic cortex; LTP, long-term potentiation; MK-801, (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-imi- maleate; mPFC, medial prefrontal cortex; NMDA, N-methyl-D- aspartate; O.D., outer diameter; PFC, prefrontal cortex; PLC, prelimbic cortex; V2MM, secondary visual cortex, mediomedial area; VTA, ven- tral tegmental area. Neuroscience 120 (2003) 283–289 0306-4522/03$30.00+0.00 © 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. doi:10.1016/S0306-4522(03)00021-6 283