4.05 Corticosterone blocks muscarinic acetylcholine receptordependent long-term depression in perirhinal cortical synapses Gilpin H, Jo J, Cho K Department <strong>of</strong> Biomedical Science, Alfred Denny Building, University <strong>of</strong> Sheffield, Western Bank, SHEFFIELD S10 2TN, UNITED KINGDOM, , Dorothy Hodgkin Building, Faculty <strong>of</strong> Medicine, University <strong>of</strong> Bristol, Whitson Street, BRISTOL BS1 3NY, UNITED KINGDOM Corticosterone (CORT), the principal glucocorticoid synthesized by the adrenal cortex in rodents, is secreted in response to stress. In particular, layer II and III <strong>of</strong> the perirhinal cortex show a high density <strong>of</strong> glucocorticoid receptor (GR) immunoreactivity (Morimoto et al. 1996). The perirhinal cortex is a transitional cortex interposed between neocortex and the hippocampal formation, and is essential for the familiarity component <strong>of</strong> recognition memory. Loss <strong>of</strong> recognition memory is a major symptom <strong>of</strong> amnesia and early stages <strong>of</strong> Alzheimer’s disease. However, little is known about whether CORT has a role in synaptic plasticity in the perirhinal cortex. Recently, cholinergic muscarinic receptors (mAChRs) have been implicated in recognition memory and long-term depression (LTD; Warburton et al. 2003; Jo et al. 2006). Therefore the present study tests whether CORT has an important role in mAChR-mediated synaptic plasticity. The current study shows that pre-incubation with 200nM CORT blocks mAChR-dependant LTD (5Hz 900 pulses at the entorhinal input <strong>of</strong> the perirhinal cortex). However, this CORT effect on LTD is abolished upon co-incubation with the glucocorticoid receptor (GR) antagonist, RU486 (500nM). Carbachol-induced LTD is also significantly reduced by CORT application. Our data suggest that CORT occludes mAChRdependant LTD in the perirhinal cortex, thus implicating an important role for CORT in recognition memory. 4.06 Dynamic regulation <strong>of</strong> N-terminal SynGAP is<strong>of</strong>orms Barnett M W, Till S, Stoney P, Papadia S, Parkinson D, Hardingham G, Kind P C University <strong>of</strong> Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK Maintenance <strong>of</strong> early phase LTP is mediated by the activation <strong>of</strong> posttranslational modification <strong>of</strong> existing molecules whilst late phase LTP is dependent on new mRNA transcription and protein synthesis. Following induction <strong>of</strong> LTP, expression <strong>of</strong> a number <strong>of</strong> immediate early genes is increased (eg. Krox24, Krox20, c-fos, c-jun). We have previously shown that the N-terminal is<strong>of</strong>orms <strong>of</strong> the neuronal RasGTPase Syngap (Syngap- A, Syngap-B and Syngap-C) have different transcription start sites and that consensus binding sites for Krox20 and Krox24 are found in close proximity to the transcription start sites <strong>of</strong> Syngap-B and Syngap-C respectively. We now provide evidence for a highly dynamic and unique spatiotemporal regulation <strong>of</strong> mRNA encoding Syngap-A, Syngap-B and Syngap-C. First, Syngap-B and Syngap-C are increased in response to activity whilst Syngap-A is not; this increase is partially dependent on the activity <strong>of</strong> NMDA receptors. Second, levels <strong>of</strong> Syngap-B and Syngap-C mRNA are selectively decreased in the hippocampi <strong>of</strong> mice lacking PLC-β1, a key signalling molecule downstream <strong>of</strong> glutamate receptors. Finally we now show that Syngap-A, Syngap-B and Syngap-C have differential temporal and spatial expression pr<strong>of</strong>iles during postnatal brain development. These findings suggest that different Syngap is<strong>of</strong>orms may regulate distinct neuronal processes in specific neuronal subpopulations. The activityindependent expression <strong>of</strong> the more abundant Syngap-A mRNA suggests that the protein it encodes may play a constitutive role in neuronal function whilst the activity-dependent is<strong>of</strong>orms (SynGAP-B and SynGAP-C) may participate in activity-dependent plasticity. 4.07 Synaptic Tagging & Capture: the search for the tag Feruza Nuritova*, Redondo R, Morris R G M, Frenguelli B G* *<strong>Neuroscience</strong>s Institute, University <strong>of</strong> Dundee & Centre for Cognitive and Neural Systems, The University <strong>of</strong> Edinburgh, Protein synthesis is required for both late long-term potentiation (L- LTP) and long-term memory (LTM). This necessitates a process by which these newly-formed plasticity-related proteins (PRPs) can be utilised exclusively by synapses at which significant sensory experience has occurred. However, associative learning enables the correlation <strong>of</strong> strong sensory experiences with weaker ones. The Synaptic Tagging and Capture hypothesis (STC) reconciles the two by proposing the creation <strong>of</strong> a lower threshold synaptic tag, which interacts with homo- or heterosynaptically generated PRPs. Thus, although the tag alone would not give rise to L-LTP/LTM, tag-PRP interactions would. We are performing dual/tri-pathway electrophysiological experiments in hippocampal slices (31–32°C) from 7-8 week old rats to test whether CaMKII is involved in tag-setting. The LTP on S0, in response to strong stimulation (3 x 100Hz/1s), measured 172.4±13.6% <strong>of</strong> baseline at 120 mins post-tetanus (n=9). Weak stimulation <strong>of</strong> S1 (1 x 100Hz/0.5s) resulted in no long-lasting potentiation (96.2±3.7%; n=3). However, if the weak tetanus was delivered 30 min after the strong tetanus, L-LTP was observed on S1 (158.3±11.6%; n=9) – ie synaptic tagging had occured. Tagging on S1 also occurred (116.0±6.7%; n=7) even if the CaMKII inhibitor KN 62 (1μM) had been present during strong stimulation <strong>of</strong> S0, which substantially reduced S0 L-LTP (115.9±3.7%; n=7). Thus, it would seem that a) parallel, heterosynaptic (presumably dopaminergic) inputs generated CaMKIIindependent PRPs on S0, which are b) recruited by the CaMKII (or CaMKII-dependent) tag on S1. 4.08 Leptin depotentiates long-term potentiation at hippocampal CA1 synapses. Milojkovic B, Harvey J <strong>Neuroscience</strong>s Institute, Ninewells Hospital & Medical School, University <strong>of</strong> Dundee, Dundee, DD1 9SY There is growing evidence that the hormone leptin plays an important modulatory role in the synaptic plastic mechanisms underlying learning and memory. Indeed leptin-insensitive rodents display impairments in hippocampal LTP and LTD, whereas at the cellular level, leptin promotes conversion <strong>of</strong> STP into LTP and it evokes a novel form <strong>of</strong> LTD. In this study we have examined the effects <strong>of</strong> leptin on potentiated hippocampal CA1 synapses using standard whole cell recordings. Transverse hippocampal slices were prepared from 14-18 day old rats, maintained at 31oC and perfused with aCSF containing picrotoxin (50µM). EPSCs were evoked by stimulation (0.033Hz) <strong>of</strong> the Schaffer collateral commissural pathway and recorded using patch pipettes filled with Cs+-based solution. In order to examine the effects <strong>of</strong> leptin on potentiated synapses, LTP was evoked by 3 trains, 250 ms apart, 20-40 stimulations at 200 Hz, which resulted in 45.79 ± 1.64% increase in synaptic transmission (n=10). Perfusion <strong>of</strong> slices with leptin (25-50nM), 30 min after LTP induction resulted in a rapid and concentration-dependent reversal <strong>of</strong> LTP (n=8). Application <strong>of</strong> 10nM leptin had no effect on LTP expression (n=2), whereas addition <strong>of</strong> 25 nM leptin reversed LTP to 97.6 ± 7.85 % <strong>of</strong> control (n=5). In contrast, perfusion with 25nM leptin failed to modify basal synaptic transmission (n=3). These data indicate that leptin, at concentrations that fail to effect basal transmission, has the capacity to reverse hippocampal LTP. These findings have important implications for the role <strong>of</strong> leptin in modulating hippocampal synaptic plasticity. Page 6/101 - 10/05/2013 - 11:11:03
4.09 ß-adrenergic modulation <strong>of</strong> in vitro hippocampal theta- and gamma-frequency oscillations Haggerty D C, Cox D J, Eden D C, Racca C, Whittington M A, LeBeau FEN University <strong>of</strong> Newcastle-upon-Tyne, SNNP, Framlington Place, Newcastle, NE2 4HH Hippocampal gamma (20-80Hz) and theta (4-15Hz) oscillations have been proposed to be involved in memory processing and visuospatial representation. The noradrenergic system has been implicated in a range <strong>of</strong> cognitive functions including arousal, attention, learning and memory. Therefore, activation <strong>of</strong> hippocampal noradrenergic receptors may have important effects on memory and visuospatial information by modulating oscillatory activity. Transverse hippocampal slices were prepared from adult male Wistar rats. Both kainate (gamma) (22.8 +/- 7.1 p
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