Role of Nitric Oxide in Classical Conditioning of Siphon Withdrawal in<i>Aplysia</i>

Antonov, Igor; Ha, Thomas; Antonova, I. V.; Moroz, Leonid L.; Hawkins, Robert D.

doi:10.1523/jneurosci.2357-07.2007

Cited by 56 publications

(52 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As in hippocampus (23), NO may stimulate soluble guanylyl cyclase leading to production of cGMP, activation of HCN current, and enhancement of NMDA current. Consistent with that idea, a NO donor enhances the HCN current in LFS motor neurons, and the pattern of results with ZD7288 during conditioning (a partial blockade that becomes larger with additional training) is similar to the pattern with injection of the NO scavenger oxymyoglobin into the motor neuron, but not the sensory neuron (37). The pattern is also similar with the NMDA receptor antagonist APV (29).…”

Section: Discussionsupporting

confidence: 80%

“…These results support the idea that NO may act through the HCN current to gate or enhance the NMDA receptor pathway in the motor neuron. If so, that effect could be analogous to the hypothesized role of NO in gating the PKA pathway in the sensory neuron (37). NO is also thought to act both presynaptically and postsynaptically in hippocampus, where it may engage additional molecular mechanisms as well (58,69,70).…”

Section: Discussionmentioning

confidence: 87%

“…However, some mammalian HCN channel types also display high sensitivity to cGMP (23,36). Both the cAMP and cGMP/NO signal transduction pathways contribute to sensitization and classical conditioning of the siphon-withdrawal reflex (25,29,37,38), suggesting that they might have HCN as one of their targets in relevant neurons during those forms of learning. Based on our results, one might expect the cGMP/NO pathway to play a relatively broader role in Aplysia than in mammals, consistent with a broad range of functions of nitrergic (NO releasing) neurons in molluscs (e.g., refs.…”

Section: Hcn Channels Expressed In Xenopus Oocytes Share Overall Simimentioning

confidence: 99%

See 2 more Smart Citations

Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia : Contribution to classical conditioning

Yang

Kuzyk

Antonov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are critical regulators of neuronal excitability, but less is known about their possible roles in synaptic plasticity and memory circuits. Here, we characterized the HCN gene organization, channel properties, distribution, and involvement in associative and nonassociative forms of learning in Aplysia californica. Aplysia has only one HCN gene, which codes for a channel that has many similarities to the mammalian HCN channel. The cloned acHCN gene was expressed in Xenopus oocytes, which displayed a hyperpolarization-induced inward current that was enhanced by cGMP as well as cAMP. Similarly to its homologs in other animals, acHCN is permeable to K + and Na + ions, and is selectively blocked by Cs + and ZD7288. We found that acHCN is predominantly expressed in inter-and motor neurons, including LFS siphon motor neurons, and therefore tested whether HCN channels are involved in simple forms of learning of the siphon-withdrawal reflex in a semiintact preparation. ZD7288 (100 μM) significantly reduced an associative form of learning (classical conditioning) but had no effect on two nonassociative forms of learning (intermediate-term sensitization and unpaired training) or baseline responses. The HCN current is enhanced by nitric oxide (NO), which may explain the postsynaptic role of NO during conditioning. HCN current in turn enhances the NMDA-like current in the motor neurons, suggesting that HCN channels contribute to conditioning through this pathway.HCN channels | learning and memory | NMDA | nitric oxide | Aplysia H yperpolarization-activated, cyclic nucleotide-gated (HCN), cation nonselective ion channels generate hyperpolarization-activated inward currents (I h ) and thus tend to stabilize membrane potential (1-3). In addition, binding of cyclic nucleotides (cAMP and cGMP) to the C-terminal cyclic nucleotide binding domain (CNBD) enhances I h and thus couples membrane excitability with intracellular signaling pathways (2, 4). HCN channels are widely important for numerous systemic functions such as hormonal regulation, heart contractility, epilepsy, pain, central pattern generation, sensory perception (4-15), and learning and memory (16-24).However, in previous studies it has been difficult to relate the cellular effects of HCN channels directly to their behavioral effects, because of the immense complexity of the mammalian brain. We have therefore investigated the role of HCN channels in Aplysia, which has a numerically simpler nervous system (25). We first identified and characterized an HCN gene in Aplysia, and showed that it codes for a channel that has many similarities to the mammalian HCN channel. We found that the Aplysia HCN channel is predominantly expressed in motor neurons including LFS neurons in the siphon withdrawal reflex circuit (26, 27). We therefore investigated simple forms of learning of that reflex in a semiintact preparation (28-30) and found that HCN current is involved in classical conditioning and enhances the ...

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 87%

Section: Hcn Channels Expressed In Xenopus Oocytes Share Overall Simimentioning

confidence: 99%

See 1 more Smart Citation

Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia : Contribution to classical conditioning

Yang

Kuzyk

Antonov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…NO release can also facilitate withdrawal responses (Antonov et al 2007), which are inconsistent with feeding (Walters et al 1981). In addition, NO is released by tissue damage (Lewin and Walters 1999).…”

Section: Block Of No Transmission Blocks Learning That Food Is Ediblementioning

confidence: 99%

“…In addition, blocking NO release in quiescent animals induces food arousal (Miller et al 2009), indicating that background NO release inhibits feeding. NO is also a transmitter in neurons functioning in the facilitation of withdrawal reflexes (Antonov et al 2007), a component of sensitization of defensive behaviors that is also incompatible with feeding (Kupfermann and Pinsker 1968). In addition, nitrergic neurites are widely dispersed in the cerebral and buccal ganglia (Moroz 2006), raising the possibility that NO is a general regulator of feeding.…”

mentioning

confidence: 99%

Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible inAplysia

Katzoff¹,

Miller²,

Susswein³

2009

Learn. Mem.

View full text Add to dashboard Cite

Memory that food is inedible in Aplysia arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that NO functions during training as a signal of attempts to swallow. However, it has been shown that NO may also be released in other contexts affecting feeding, raising the possibility that its role in learning is unrelated to signaling attempts to swallow. We confirmed that NO during learning signals attempts to swallow, by showing that a variety of behavioral effects on feeding of blocking or adding NO do not affect learning and memory that a food is inedible. In addition, histamine had effects similar to NO on learning that food is inedible, as expected if the transmitters are released together when animals attempt to swallow. Blocking histamine during training blocked long-term memory, and exogenous histamine substituted for attempts to swallow. NO also substituted for histamine during training. Histamine at concentrations relevant to learning activates neuron metacerebral cell (MCC). However, MCC activity is not a good monitor of attempts to swallow during training, since the neuron responds equally well to other stimuli. These findings support and extend the hypothesis that NO and histamine signal efforts to swallow during learning, acting on targets other than the MCC that specifically respond to attempts to swallow.

show abstract

Mapping of neuropeptide Y expression in Octopus brains

Winters

Polese

Cosmo

et al. 2020

Journal of Morphology

View full text Add to dashboard Cite

Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation in Octopus. However, little is known about the precise molecular circuitry of NPY‐mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout the Octopus central nervous system. The sequence analysis of Octopus NPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians. In situ hybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY‐dependent modulation in Octopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of the Octopus feeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in various Octopus behaviors.

show abstract

Role of Nitric Oxide in Classical Conditioning of Siphon Withdrawal inAplysia

Cited by 56 publications

References 79 publications

Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia : Contribution to classical conditioning

Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia : Contribution to classical conditioning

Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible inAplysia

Mapping of neuropeptide Y expression in Octopus brains

Contact Info

Product

Resources

About