(B) C-fos counts for the lidocaine group (% of control) for each coronal section through the ventral hippocampus at intervals of 150 m. that performance was impaired during the infusion period. The critical test occurred 1 week after the lesion was reversed. We found that retention of the water maze Rabbit Polyclonal to TEAD1 recovered to control levels. Accordingly, sustained hippocampal activity following training is not obligatory for either the maintenance of long-term spatial memory or its subsequent retrieval. Keywords:reversible lesion, minipump, rat, water maze, lidocaine == INTRODUCTION == After memory is initially acquired, it remains subject to Harmine modification by a variety of treatments, including disruption of hippocampal function (McGaugh, 2002;Martin and Clark, 2007). Gradually, memory becomes resistant to disruption, a process that in experimental animals typically happens across a period of a few weeks (Squire et al., 2004;Frankland and Bontempi, 2005). Little is known about how this process occurs or what exactly happens to stored representations when memory space is disrupted. Here we explored the effect of chronic disruption of hippocampal activity within the long-term maintenance of hippocampus-dependent memory space. The water maze has been the benchmark task for spatial learning and memory space in the rodent. A substantial literature shows that both acquisition and manifestation of memory space in the water maze requires the hippocampus (Bolhuis et al. 1994,Mumby et al. 1999,Sutherland et al. 2001;Martin et al., 2005;Broadbent et al., 2006;Clark et al., 2005a,b,2007). However, the importance of the hippocampus during the retention interval itself is poorly understood. In basic principle, this issue could be tackled by reversibly disrupting hippocampal function for a lengthy period during the retention interval. Only a few studies have taken this approach. In two studies, pharmacological blockade of AMPA receptors in the rat hippocampus for 7 days after water maze training completely impaired subsequent overall performance (Riedel et al., 1999;Micheau et al., 2004). Two additional studies used a different manipulation, obstructing NMDA-mediated synaptic plasticity in the hippocampus for 7 days after water maze teaching, and these studies obtained conflicting results (no impairment,Day and Morris, 2001; impairment,Shimizu et al., 2000). We have used a sodium channel blocker to reversibly inactivate the rat hippocampus for 1 week following training within the water maze. Specifically, we infused lidocaine into dorsal hippocampus using osmotic minipumps. The query of interest was whether chronic disruption of neuronal activity in the hippocampus after teaching would abolish memory space for the water maze task or whether memory space storage would survive continuous disruption of hippocampal activity. == MATERIALS AND METHODS == == Subjects == The subjects were 142 nave male, Long-Evans rats weighing 300350 g at the beginning of the study. One hundred eighteen rats underwent cannula implantation surgery, behavioral teaching, minipump implantation, and intrahippocampal infusion of lidocaine (n= 58) or aCSF (n= 60). Six rats received behavioral teaching and sham surgeries and served as an untreated control group. Eighteen rats were infused with aCSF (n= 9) or lidocaine (n= 9) and then utilized for immunohistochemistry to determine the degree of Harmine lidocaine inactivation. All rats were housed separately and maintained on a 12:12 h light:dark cycle. Food and water were available ad libitum. Prior to training, rats were implanted bilaterally with guidebook cannulae in the dorsal hippocampus. == Harmine Stereotaxic Bilateral Hippocampal Cannula Implants Harmine == Anesthesia was managed throughout surgery with isoflurane gas (0.82.0% isoflurane delivered in O2at 1 l min1). The rat was placed in a stereotaxic instrument (Kopf Tools, Tujunga, CA), and the incisor pub was modified until Bregma was level with Lambda. Sterile, stainless steel guidebook cannulae (22 gauge; Plastics One, Roanoke, VA) were implanted bilaterally into the dorsal hippocampus (millimeters from Bregma, AP = 4.3, ML = 3.5, DV = 2.0;Paxinos and Watson, 1998). Anchoring screws and dental care acrylic secured the guidebook cannula to the skull. The skin was approximated round the implant and sutured in place. At completion of surgery, a dummy cannula (Plastics One) was put into each guidebook cannula to keep up patency. Each rat received Baytril (Bayer Corporation, Shawnee Mission, KS) antibiotic for prophylaxis against illness (0.2 ml s.c. for 2 days). All rats were given at least 4-day time recovery before water maze training began. For the six rats receiving sham surgeries, the skin above the skull was opened and then sutured. == Minipump Implantation == On the day following completion of water maze teaching, rats were anesthetized with isoflurane gas and secured in the stereotaxic instrument. Sterile osmotic minipumps (Alzet; Durect Corporation, Cupertino, CA) were implanted under the pores and skin of the back of each rat. Each minipump was attached via sterile polyethylene tubing (Durect Corporation) to sterile internal cannula (28 gauge; Plastics One). In the beginning we used three different infusion rates (1, 2.5, and 5 l/hr) to determine.
(B) C-fos counts for the lidocaine group (% of control) for each coronal section through the ventral hippocampus at intervals of 150 m
