Nitric oxide‐dependent long‐term depression but not endocannabinoid‐mediated long‐term potentiation is crucial for visual recognition memory

Francesco Tamagnini,E Clea Warburton,Giorgio Aicardi,Costanza Burattini,Zafar I Bashir,Gareth Barker

doi:10.1113/jphysiol.2013.254862

Francesco Tamagnini, E Clea Warburton + Show 4 more

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https://doi.org/10.1113/jphysiol.2013.254862

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Abstract

Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory.

Highlights

The perirhinal cortex (Prh) is essential for the ability to discriminate between novel and familiar individual stimuli (Brown & Aggleton, 2001), and the processes underlying activity-dependent synaptic plasticity in Prh may provide clues about the cellular and molecular correlates of this component of recognition memory (Warburton et al 2003, 2005; Griffiths et al 2008; Massey et al 2008; Seoane et al 2009; Brown et al 2010)
To investigate the role of NO-dependent signalling in CCh-long-term depression (LTD), the nitric oxide synthase (NOS) inhibitor L-N Gnitroarginine methyl ester hydrochloride (L-NAME) was bath applied at different concentrations
Our results are the first to demonstrate that LTD in Prh relies on NO

Summary

Introduction

The perirhinal cortex (Prh) is essential for the ability to discriminate between novel and familiar individual stimuli (Brown & Aggleton, 2001), and the processes underlying activity-dependent synaptic plasticity in Prh may provide clues about the cellular and molecular correlates of this component (i.e. familiarity discrimination) of recognition memory (Warburton et al 2003, 2005; Griffiths et al 2008; Massey et al 2008; Seoane et al 2009; Brown et al 2010). Retrograde signalling is critical in synaptic plasticity, co-ordinating pre- and postsynaptic changes following induction of long-term potentiation (LTP) or long-term depression (LTD). NO is synthesized postsynaptically in neurones and blood vessels by constitutive isoforms of nitric oxide synthase (neuronal, nNOS; endothelial, eNOS) that are activated by Ca2+–calmodulin (reviewed by Garthwaite & Boulton, 1995; Garthwaite, 2008; Steinert et al 2010). Nitric oxide can play a role in retrograde signalling in LTD in the cerebellum, hippocampus and prefrontal cortex (Reyes-Harde et al 1999; Shin & Linden, 2005; Huang & Hsu, 2010) and in LTP in the hippocampus and visual cortex (Arancio et al 1995, 1996, 2001; Wang et al 2005; Haghikia et al 2007). NO has been implicated in learning and memory, including spatial (Bohme et al 1993) and motor learning (Allen & Steinmetz 1996; Nagao et al 1997)

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