Inhibition of Nitric Oxide Synthase Impairs Early Olfactory Associative Learning in Newborn Rats

Samama, Brigitte; Boehm, Nelly

doi:10.1006/nlme.1998.3869

Cited by 31 publications

(22 citation statements)

References 59 publications

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“…In the honeybee, NO is involved in habituation (Muller and Hildebrandt 2002) and long-term memory in associative olfactory learning (Muller 1996). NO also plays an important role in olfactory learning in infant rats (Samama and Boehm 1999) and sheep (Kendrick et al 1997). Besides olfactory learning, NO is involved in various types of learning, including appetitive learning for chemical stimuli in Lymnaea (Kemenes et al 2002) and tactile (Robertson et al 1994) and visual (Robertson et al 1996) learning in the octopus.…”

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confidence: 99%

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Nitric oxide is involved in appetitive but not aversive olfactory learning in the land mollusk Limax valentianus

Yabumoto¹,

Takanashi²,

Kirino³

et al. 2008

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The land slug Limax performs both aversive and appetitive olfactory learning, and we investigated neurotransmitters involved in each type of learning. Slugs were conditioned by presenting a vegetable juice (appetitive conditioning) or a mixture of vegetable juice and quinidine (aversive conditioning), and the latency to reach the juice became shorter (appetitive conditioning) or longer (aversive conditioning) after conditioning. L-NAME injected either before conditioning or testing blocked the reduction in latency in appetitive conditioning but had no significant effects in aversive conditioning. 5,7-dihydroxytryptamine had no significant effects in appetitive conditioning. These results suggest different mechanisms for appetitive and aversive learning.The land mollusk Limax has a highly developed olfactory system and performs olfactory learning. Both aversive (Gelperin 1975;Sahley et al. 1981) and appetitive (Sahley et al. 1990) olfactory learning have been reported, and therefore, it is possible to compare these two forms of learning in Limax. Aversive learning occurs when an odor is associated with an aversive chemical or electrical shock, and appetitive learning occurs when an odor is associated with food. So far, aversive learning has been more extensively studied than appetitive learning. Our previous study showed using the serotonergic neurotoxin 5,7-dihydroxytryptamine (DHT), which reduces the serotonin content in the CNS to less than half, that serotonin is essential for aversive learning (Shirahata et al. 2006). However, it is not known whether appetitive learning also depends on serotonin, or whether it requires other neurotransmitters.Nitric oxide (NO) synthase is abundant in the procerebrum (PC) (Fujie et al. 2002(Fujie et al. , 2005, which is a region of the cerebral ganglion essential for olfactory learning (Kasai et al. 2006). NO applied extrinsically modulates the rhythmic activity of the local field potential (LFP) of the PC (Gelperin 1994;Gelperin et al. 2000). These observations suggest significance of NO in olfactory processing in Limax. In Helix pomatia, a related land mollusk, appetitive learning is blocked by N -nitro-L-arginine methyl ester (L-NAME), a blocker of NO synthase. In the present work, we examine using L-NAME whether NO is involved in appetitive and aversive learning in Limax. We examine dependence of the acquisition and retrieval stages on NO separately. We also examine dependence of appetitive learning on serotonin using DHT.Limax valentianus 2-4 mo old from the laboratory colony were used. The slugs were freely fed with a mixture of rat chow (Oriental Yeast), wheat starch (Wako Pure Chemical), and mixed vitamins (Oriental Yeast), until 5 d before the experiment. The slugs were kept under the light/dark cycle of 10 h/14 h, and conditioning and testing were done within 4 h from the onset of the dark period. Five days before conditioning, the slugs were moved to individual boxes floored with moistened filter paper and starved. The training and testing were made on a glass plat...

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“…In Aplysia, NO is involved in memory on food (Katzoff et al 2002). NO is also involved in other types of learning in vertebrates (Li et al 1995;Kendrick et al 1997;Qiang et al 1997;Samama and Boehm 1999) and is known as essential for long-term changes in synaptic transmission (Schuman and Madison 1991;Daniel et al 1993).…”

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confidence: 99%

Nitric oxide is involved in appetitive but not aversive olfactory learning in the land mollusk Limax valentianus

Yabumoto¹,

Takanashi²,

Kirino³

et al. 2008

Learn. Mem.

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“…In accordance with these findings, fear conditioning to contextual, visual, or auditory cues has been shown to be impaired with nNOS inhibitors (Resstel et al 2008;Kelley et al 2009Kelley et al , 2011Ota et al 2010;Overeem and Kokkinidis 2012). Furthermore, associative olfactory learning in pups was blocked by L-NAME when given before training (Samama and Boehm 1999), and administration of a nNOS blocker prevented maternal memory formation (Kendrick et al 1997). Overall, these results reveal an important role for NO signaling in the consolidation and retention of long-term memory to olfactory cues.…”

Section: Olfactory Fear Learning Impairment Due To Reductions In Nnosmentioning

confidence: 70%

Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization

2013

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Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice lacking nNOS received six training trials, each consisting of an odor-CS co-terminating with a foot shock-US. Mice showed reduced freezing responses to the trained odor 24 h and 7 d after training, compared to wild-type mice. Pretraining systemic injections of the NO donor, molsidomine, rescued fear retention in nNOS knockout mice. In wildtype mice, pretraining systemic injections of L-NAME, a nonspecific nNOS blocker, disrupted odor-CS fear retention in a dose-dependent manner. To evaluate whether NO signaling is involved in generalization of fear memories, nNOS knockout mice and wild-type mice receiving L-NAME were trained to one odor and tested with a series of similar odors. In both cases, we found increased generalization, as measured by increased freezing to similar, unpaired odors. Despite the impairment in fear memory retention and generalization, neither mice receiving injections of L-NAME nor nNOS knockout mice showed any deficits in either novel odor investigation time or odor habituation, suggesting intact olfactory perception and short-term memory olfactory learning. These results support a necessary role for neuronal NO signaling in the normal expression and generalization of olfactory conditioned fear.The ability to learn and retain memories is dependent on several transmitters. Currently, there is much interest in the involvement of nitric oxide (NO) signaling in long-term memory formation (Bredt and Snyder 1992;Hawkins et al. 1994;Garthwaite 2008;Kelley et al. 2011). NO is generated from the amino acid L-arginine by the enzyme NO synthase (NOS) and functions as a retrograde neurotransmitter. Due to the diffusible nature of NO and its relationship with NMDA receptor activation, neurons containing the neuronal isoform of NOS (nNOS) could be involved in driving synaptic strength changes during learning processes such as longterm memory Zhuo et al. 1994;Garthwaite 2008).Fear conditioning is a useful tool in studying the neuronal mechanisms involved in the formation of long-term memory and fear-related systems. Rodents can quickly and reliably learn a fear association between a conditioned stimulus (CS) and an aversive stimulus (US), such as a foot shock (Young and Fanselow 1992). The role nNOS plays in fear learning has been investigated using contextual fear conditioning, as well as visual and auditory cues as the CS (Schafe et al. 2005;Kelley et al. 2010Kelley et al. , 2011Overeem et al. 2010). And although the nNOS inhibitor 7-nitroindazole showed no disruption in the acquisition and expression of the contextual fear conditioning (Maren 1998), it was demonstrated that animals lacking the nNOS gene (Nos1or nNOS knockout) have shown deficits in fear condit...

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“…Specifically in olfaction, NOS inhibition affects odor associations in sheep (Kendrick et al, 1997), newborn rat pups (Samama and Boehm, 1999) and land slugs (Yabumoto et al, 2008). Interestingly, an already-learned association is unaffected by NOS inhibition (Yamada et al, 1995;Müller, 1996;Kendrick et al, 1997;Samama and Boehm, 1999;Yeh and Powers, 2005), suggesting that the role of NO is specific to learning processes and not retrieval. In honeybees, NOS inhibition experiments reveal that learning acquisition is intact, but a specific form of long-term memory is impaired (Müller, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…Insights from other animal species have demonstrated that NOS inhibition affects a wide variety of learning and memory paradigms that include contextual fear learning in mice (Kelley et al, 2010), delayed visual recall in monkeys (Prendergast et al, 1997a), negative patterning in turtles (Yeh and Powers, 2005) and spatial navigation in rats and mice (Prendergast et al, 1997b;Mutlu et al, 2011). Specifically in olfaction, NOS inhibition affects odor associations in sheep (Kendrick et al, 1997), newborn rat pups (Samama and Boehm, 1999) and land slugs (Yabumoto et al, 2008). Interestingly, an already-learned association is unaffected by NOS inhibition (Yamada et al, 1995;Müller, 1996;Kendrick et al, 1997;Samama and Boehm, 1999;Yeh and Powers, 2005), suggesting that the role of NO is specific to learning processes and not retrieval.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide affects short-term olfactory memory in the antennal lobe ofManduca Sexta

Gage

Daly

Nighorn

2013

Journal of Experimental Biology

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SUMMARYNitric oxide (NO) is thought to play an important neuromodulatory role in olfaction. We are using the hawkmoth Manduca sexta to investigate the function of NO signaling in the antennal lobe (AL; the primary olfactory network in invertebrates). We have found previously that NO is present at baseline levels, dramatically increases in response to odor stimulation, and alters the electrophysiology of AL neurons. It is unclear, however, how these effects contribute to common features of olfactory systems such as olfactory learning and memory, odor detection and odor discrimination. In this study, we used chemical detection and a behavioral approach to further examine the function of NO in the AL. We found that basal levels of NO fluctuate with the daily light cycle, being higher during the nocturnal active period. NO also appears to be necessary for short-term olfactory memory. NO does not appear to affect odor detection, odor discrimination between dissimilar odorants, or learning acquisition. These findings suggest a modulatory role for NO in the timing of olfactory-guided behaviors. Supplementary material available online at

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Inhibition of Nitric Oxide Synthase Impairs Early Olfactory Associative Learning in Newborn Rats

Cited by 31 publications

References 59 publications

Nitric oxide is involved in appetitive but not aversive olfactory learning in the land mollusk Limax valentianus

Nitric oxide is involved in appetitive but not aversive olfactory learning in the land mollusk Limax valentianus

Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization

Nitric oxide affects short-term olfactory memory in the antennal lobe ofManduca Sexta

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