Anterograde Signaling by Nitric Oxide: Characterization andIn Vitro Reconstitution of an Identified Nitrergic Synapse

Nitric oxide (NO) is recognized as a signaling molecule in the CNS where it is a candidate retrograde neurotransmitter. Here we provide direct evidence that NO mediates slow excitatory anterograde transmission between the NO synthase (NOS)-expressing B2 neuron and an NO-responsive follower neuron named B7nor. Both are motoneurons located in the buccal ganglia of the snail Lymnaea stagnaliswhere they participate in feeding behavior. Transmission between B2 and B7nor is blocked by inhibiting NOS and is suppressed by extracellular scavenging of NO. Furthermore, focal application of NO to the cell body of the B7nor neuron causes a depolarization that mimics the effect of B2 activity. The slow interaction between the B2 and B7nor neurons can be re-established when the two neurons are cocultured, and it shows the same susceptibility to NOS inhibition and NO scavenging. In cell culture we have also examined spatial aspects of NO signaling. We show that before the formation of an anatomical connection, the presynaptic neuron can cause depolarizing potentials in the follower neuron at distances up to 50 μm. The strength of the interaction increases when the distance between the cells is reduced. Our results suggest that NO can function as both a synaptic and a nonsynaptic signaling molecule.

[1]  H. Stephen,et al.  Solubilities of inorganic and organic compounds , 1963 .

[2]  P. Benjamin,et al.  Neural network controlling feeding in Lymnaea stagnalis: Immunocytochemical localization of myomodulin, small cardioactive peptide, buccalin, and FMRFamide‐ related peptides , 1994, The Journal of comparative neurology.

[3]  J. Hibbs,et al.  L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. , 1987, Journal of immunology.

[4]  I. Kupfermann,et al.  Modulatory synaptic actions of an identified histaminergic neuron on the serotonergic metacerebral cell of Aplysia , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  Alan Gelperin,et al.  Nitric oxide mediates network oscillations of olfactory interneurons in a terrestrial mollusc , 1994, Nature.

[6]  A. Bulloch,et al.  Nerve growth factor (NGF) induces sprouting of specific neurons of the snail, Lymnaea stagnalis. , 1991, Journal of neurobiology.

[7]  R. M. Rose,et al.  Morphology of Identified Neurones in the Buccal Ganglia of Lymnaea Stagnalis , 1979 .

[8]  J. Wood,et al.  Models of the diffusional spread of nitric oxide: Implications for neural nitric oxide signalling and its pharmacological properties , 1994, Neuropharmacology.

[9]  J. Picot,et al.  Molecular characterization of NOS in a mollusc: expression in a giant modulatory neuron. , 1998, Journal of neurobiology.

[10]  J. Jacklet.  Nitric oxide is used as an orthograde cotransmitter at identified histaminergic synapses. , 1995, Journal of neurophysiology.

[11]  W. Winlow,et al.  Nitric oxide synthase-immunoreactive cells in the CNS and periphery of Lymnaea. , 1994, Neuroreport.

[12]  S. Lipton,et al.  Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex , 1992, Neuron.

[13]  C. Hölscher.  Nitric oxide, the enigmatic neuronal messenger: its role in synaptic plasticity , 1997, Trends in Neurosciences.

[14]  A. Bulloch,et al.  Putative No-Synthesizing Neurons of Lymnaea in Vivo and in Vitro , 1993 .

[15]  G. Kemenes,et al.  Neural modulation of gut motility by myomodulin peptides and acetylcholine in the snail Lymnaea. , 1998, Journal of neurophysiology.

[16]  J. Lancaster,et al.  Simulation of the diffusion and reaction of endogenously produced nitric oxide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  S. Snyder,et al.  Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  K. Staras,et al.  Behavioral role for nitric oxide in chemosensory activation of feeding in a mollusc , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  C. Elliott,et al.  Interactions of the slow oscillator interneuron with feeding pattern-generating interneurons in Lymnaea stagnalis. , 1985, Journal of neurophysiology.

[20]  P. Benjamin,et al.  A cholinergic modulatory interneuron in the feeding system of the snail, Lymnaea. , 1993, Journal of neurophysiology.

[21]  P. A. Getting.  Mechanisms of pattern generation underlying swimming in Tritonia. I. Neuronal network formed by monosynaptic connections. , 1981, Journal of Neurophysiology.

[22]  J. G. Mcelligott,et al.  Cerebellar nitric oxide is necessary for vestibulo-ocular reflex adaptation, a sensorimotor model of learning. , 1995, Journal of neurophysiology.

[23]  Solomon H. Snyder,et al.  Nitric oxide, a novel neuronal messenger , 1992, Neuron.

[24]  W. Winlow,et al.  The distribution of three wide-acting synaptic inputs to identified neurons in the isolated brain of , 1981 .

[25]  N. Hartell,et al.  Strong Activation of Parallel Fibers Produces Localized Calcium Transients and a Form of LTD That Spreads to Distant Synapses , 1996, Neuron.

[26]  K. Staras,et al.  Pattern-Generating Role for Motoneurons in a Rhythmically Active Neuronal Network , 1998, The Journal of Neuroscience.

[27]  R. M. Rose,et al.  Central generation of bursting in the feeding system of the snail, Lymnaea stagnalis. , 1979, The Journal of experimental biology.

[28]  J. Garthwaite,et al.  Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain , 1988, Nature.

[29]  R. M. Rose,et al.  The relationship of the central motor pattern to the feeding cycle of Lymnaea stagnalis. , 1979, The Journal of experimental biology.

[30]  R. M. Rose,et al.  INTERNEURONAL CONTROL OF FEEDING IN THE POND SNAIL LYMNAEA STAGNALIS I. INITIATION OF FEEDING CYCLES BY A SINGLE BUCCAL INTERNEURONE , 1981 .

[31]  H. Chiel,et al.  An identified histaminergic neuron modulates feeding motor circuitry in Aplysia , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  M. O'Shea,et al.  Nitric oxide compartments in the mushroom bodies of the locust brain , 1998, Neuroreport.

[33]  C. Elliott,et al.  Interactions of pattern-generating interneurons controlling feeding in Lymnaea stagnalis. , 1985, Journal of neurophysiology.

[34]  I. Singh,et al.  Modulation of Endogenous Antioxidant Enzymes by Nitric Oxide in Rat C6 Glial Cells , 1997 .

[35]  J Garthwaite,et al.  Nitric oxide signaling in the central nervous system. , 1995, Annual review of physiology.

[36]  T. Teyke.  Nitric oxide, but not serotonin, is involved in acquisition of food-attraction conditioning in the snail Helix pomatia , 1996, Neuroscience Letters.

[37]  Optical monitoring of movements in small animals and in semi-intact preparations , 1995, Journal of Neuroscience Methods.

[38]  J. Bains,et al.  Nitric oxide depolarizes Type II paraventricular nucleus neurons in vitro , 1997, Neuroscience.

[39]  T. Dawson,et al.  Gases as biological messengers: nitric oxide and carbon monoxide in the brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.