The nitric oxide‐cyclic GMP pathway and synaptic plasticity in the rat superior cervical ganglion

Abstract

1 We have investigated the possibility that nitric oxide (NO) and soluble guanylyl cyclase, an enzyme that synthesizes guanosine 3':5'-cyclic monophosphate (cyclic GMP) in response to NO, contributes to plasticity of synaptic transmission in the rat isolated superior cervical ganglion (SCG). 2 Exposure of ganglia to the NO donor, nitroprusside, caused a concentration-dependent accumulation of cyclic GMP which was augmented in the presence of the phosphodiesterase inhibitor, 3-isobutyl-lmethylxanthine. The compound, IH-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, completely blocked this cyclic GMP response.3 As assessed by extracellular recording, nitroprusside (100 gM) and another NO donor, Snitrosoglutathione (30 gM) increased the efficacy of ganglionic synaptic transmission in response to electrical stimulation of the preganglionic nerve, an effect that was reversible and which could be replicated by the cyclic GMP analogue, 8-bromo-cyclic GMP. Ganglionic depolarizations resulting from stimulation of nicotinic receptors with carbachol were not increased by nitroprusside. The potentiating actions of the NO donors on synaptic transmission, but not that of 8-bromo-cyclic GMP, were inhibited by ODQ. 4 Brief tetanic stimulation of the preganglionic nerve resulted in a long-term potentiation (LTP) of synaptic transmission that was unaffected by ODQ, either in the absence or presence of the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG, 100 ,UM). A lack of influence of L-NOARG was confirmed in intracellular recordings of LTP of the excitatory postsynaptic potential. Furthermore, under conditions where tetanically-induced LTP was saturated, nitroprusside was still able to potentiate synaptic transmission, as judged from extracellular recording. 5 We conclude that NO is capable of potentiating ganglionic neurotransmission and this effect is mediated through the stimulation of soluble guanylyl cyclase and the accumulation of cyclic GMP. However, this potentiation is distinct from LTP of nicotinic synaptic transmission, in which neither NO nor soluble guanylyl cyclase appear to participate.

Retrograde Carbon Monoxide Is Required for Induction of Long-Term Potentiation in Rat Superior Cervical Ganglion

“…However, it has been shown that, at the level of the concentration used in the present study, ZnPP is unlikely to produce inhibition of guanylate cyclase (Luo and Vincent, 1994;Zakhary et al, 1996). Furthermore, the present experiments clearly showed that ZnPP has no effect on previously established LTP, which requires activation of guanylate cyclase as has been demonstrated previously (K. A. Alkadhi, unpublished observation) (Briggs, 1992;Scott and Bennett, 1993;Southam et al, 1996). Additionally, failure of ZnPP to inhibit sodium nitroprusside-induced enhancement of ganglionic transmission indicates that guanylate cyclase is not inhibited by ZnPP in our experiments (Verma et al, 1993).…”

“…In contrast, NO synthase exists in sympathetic preganglionic neurons (Blottner and Baumgarten, 1992;Dun et al, 1992;Valtschanoff et al, 1992) and has been localized mainly within preganglionic nerve terminals in sympathetic ganglia (Dun et al, 1993;Morris et al, 1993;Saito et al, 1994;Anderson et al, 1995;Okamura et al, 1995;Klimaschewski et al, 1996b). In both the CNS and autonomic ganglia, exogenous NO, by itself, can produce prolonged enhancement of synaptic transmission without the need for tetanic stimulation (Bohme et al, 1991;Scott and Bennett, 1993;Southam et al, 1996). In contrast, exogenous CO in sympathetic ganglia (present results), as well as in hippocampal slices (Zhuo et al, 1993), must be accompanied by tetanic activation of presynaptic nerve fibers to produce enhancement of synaptic transmission.…”

Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice

“…It could be argued that mechanisms other than neurogenesis may affect olfactory learning in NOS‐treated animals, based on the proposed involvement of NO in long‐term potentiation and synaptic remodelling (Schuman & Madison, 1991; Williams et al ., 1993; Southam et al ., 1996). However, the participation of NO in these events has been demonstrated in acute or short‐term experiments in which the effects of minutes to hours of NOS inhibition were evaluated.…”

Role of phosphodiesterase 5 in synaptic plasticity and memory

“…Various studies are now focusing on the role of PDEs in the CNS and on the potential use of PDE inhibitors for nervous system disorders. This can be explained by the presence of PDEs in various regions of the CNS (Ariano and Appleman 1979; Shinozawa and Bitensky 1981; Epplen et al 1982; Shotwell 1983; Kariya and Dage 1988; Repaske et al 1993; Lobban et al 1994; Polli and Kincaid 1994; Yan et al 1994; Lal et al 1996; Cherry and Davis 1999; Shakur et al 2000; Andreeva et al 2001; D’Sa et al 2002; Suvarna and O’Donnel 2002; van Staveren et al 2002; Houslay and Adams 2003; Kobayashi et al 2003; Noyama and Maekawa 2003; Pitts et al 2004; Reyes-Irisarri et al 2005) and to the fact that cAMP and cGMP have been recognized as secondary messengers of various neuronal phenomena such as synaptic plasticity (Dismukes and Daly 1976; Kandel and Schwartz 1982; Yovell et al 1987; Dixon and Atwood 1989; Storozhuk and Balaban 1990; Shibuki and Okada 1991; Zhong and Wu 1991; Zhong et al 1992; Arancio et al 1995; Wu et al 1995; Southam et al 1996; Lu et al 1999; Renger et al 2000; Yoshimura and Kato 2000; Bon and Garthwaite 2001, 2003; Esteban et al 2003; Waltereit and Weller 2003; Wang and Storm 2003; Barnstable et al 2004; Feil et al 2005; Makhinson et al 2006; Liu et al 2007; Wu et al 2007). …”