Neurons Controlling Aplysia Feeding Inhibit Themselves by Continuous NO Production

Nimrod Miller,Abraham J Susswein,Itay Hurwitz,Ravit Saada,Shlomi Fishman,Björn Brembs

doi:10.1371/journal.pone.0017779

Abstract

BackgroundNeural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking?Methodology/Principal FindingsApplying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS) blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest.Conclusion/SignificanceSelf-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior.

Highlights

Release of the unconventional neurotransmitter nitric oxide (NO) is contingent on the activity of an enzyme, nitric oxide synthase (NOS), rather than on depolarization-dependent vesicle release
We examined the possibility that in addition to being released by stimuli signaling aspects of feeding, NO is produced in the absence of elicited neural activity in the Aplysia buccal ganglia
Since NO is a modulator of central pattern generators in other systems [11,17,18,20,32], and since NO affects aspects of Aplysia feeding [8], we examined the possibility that NO production within the buccal ganglia has a role in modulating the buccal ganglia CPG

Summary

Introduction

Release of the unconventional neurotransmitter nitric oxide (NO) is contingent on the activity of an enzyme, nitric oxide synthase (NOS), rather than on depolarization-dependent vesicle release. We have examined the possible control of key neurons affecting Aplysia feeding by NO in the absence of spiking. Neural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity be affected by NO produced in neurons in the absence of spiking?. Two aspects of nitrergic inhibition of Aplysia feeding are to date unique: 1) NO is produced in neurons in the absence of spiking; 2) NO causes self-inhibition by blocking an inward leak current. Many neurons in the ganglion are nitrergic, suggesting that NO released from the CPG modulates it. NO release affecting the nervous system without neural activity is found in the hippocampus, where both elicited and background NO release facilitate long-term potentiation (LTP) [16,66]. Release of NO from capillaries onto neurons occurs in the optic nerves of mammals [67]

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