Chanisms of LTD inside the striatum, cortex and hippocampus (Robbe et al. 2002; Lafourcade et al. 2007; Sergeeva et al. 2007; Yasuda et al. 2008) and in hippocampal and amygdala-dependentCassociative studying and memory (Marsicano et al. 2002; Varvel et al. 2007). Interestingly, there is no evidence concerning the function of retrograde signalling systems in Prh synaptic plasticity and so the link involving these signalling systems and Prh-dependent understanding is still to become established. For that reason, in this study we address the roles of NOand eCB-dependent signalling in each LTP and LTD in Prh in vitro and in visual recognition memory in vivo. We demonstrate that inhibition of nitric oxide synthase (NOS) and of soluble guanylate cyclase (sGC) prevents LTD but not LTP and that inhibition of cannabinoid signalling, by bath application of AM251 (1 M), a CB1 antagonist, prevents LTP but not LTD in vitro. We then show that inhibition of NOS but not inhibition of CB1 receptors impairs the familiarity discrimination element of recognition memory. These data recommend a reciprocal involvement of NO and eCBs in perirhinal LTD and LTP, respectively, and point to a part for NO in visual recognition memory acquisition, providing additional confirmation that depression-like phenomena in Prh might represent the cellular correlate of this form of memory, as previously recommended (Warburton et al. 2003; Griffiths et al. 2008; Massey et al. 2008; Seoane et al. 2009).MethodsAnimalsAdult male pigmented (Dark Agouti, DA) rats (22050 g; Bantin and Kingman, Hull, UK), for in vivo experiments, and postnatal day 285 male DA (Bantin and Kingman, Hull, UK) or albino rats (Sprague awley, SD; Charles River, Margate, UK), for in vitro electrophysiology, were maintained on a 12 h light2 h dark cycle, with the dark phase in the course of normal daylight. All experiments had been performed in accordance with the UK Animals (Scientific Procedures) Act 1986 and also the European Neighborhood Recommendations on animal care, and had the approval on the Ethical Assessment Committees with the Universities of Bristol and Bologna.2013 The Authors. The Journal of Physiology published by John Wiley Sons Ltd on behalf with the Physiological Society.J Physiol 591.Perirhinal cortex synaptic plasticity and recognition memoryIn vitro experimentsSlice preparation. Each animal was anaesthetized with amixture of oxygen and isoflurane or halothane and subsequently decapitated. The brain was quickly removed and placed in ice-cold (2 C), oxygenated (95 O2 CO2 ) artificial cerebrospinal fluid (aCSF) containing (mM): 125 NaCl, 2.5 KCl, 1.2 NaH2 PO4 , 1.2 MgCl2 , two.4 CaCl2 , 26 NaHCO3 and 11 glucose. The cerebellum and the frontal and parietal lobes were removed with single scalpel cuts. The sample was then glued on a stainless-steel stage and right away placed within the slicing IKK-β Storage & Stability chamber of a vibratome (WPI Europe, Berlin, Germany) filled with ice-cold, oxygenated aCSF. Horizontal slices (400 m thick), comprising hippocampus, Prh and lateral entorhinal cortex, have been obtained and then left to recover (600 min) in oxygenated aCSF at space temperature. Just after recovery, 1 single slice was placed in a submerged recording chamber, maintained at 32 C and continuously perfused with oxygenated aCSF delivered at a flow price of two ml min-1 .Electrophysiological recordings. Immediately after acclimatization (atleast 30 min), square mGluR6 drug existing pulses (duration 0.two ms) had been applied each and every 30 s (0.033 Hz) through a stimulating electrode placed in the Prh superficial layers (approxi.
