The long-term objective of this research is to understand the special signaling role played by nitric oxide (NO) in the central nervous system (CNS). This unusual messenger was discovered only recently hence comparatively little is known about its role in the brain. NO is a free radical synthesized and released from cells by NO synthase (NOS) and one of its predominant effects is to increase cellular cGMP. Because NO diffuses quickly in aqueous solutions and across lipid membranes it seems well suited to coordinating, or modulating, widely separated neurons. This raises an interesting problem, if NO permeates a relatively large volume of the CNS then receiving neurons may not be able to recognize the source of the signal. In fact NO release can generate slow excitatory postsynaptic potentials in target cells in a mollusk (Jacklet, J Neurophys. 1995 74:891-5; Park, et al., J Neurosci, 1998. 18:5463-76). This raises important questions about target specificity, information transfer and the behavioral relevance of NO.

     Our research explores these questions using a model system (the ventral nerve cord of the insect Manduca sexta) in which NO-producing and receiving neurons have been individually identified and mapped (Zayas et al. J Comp. Neurol. 2000. 419, 422-438), and NO/cGMP signaling can be isolated pharmacologically (Qazi and Trimmer, J Comp. Physiol. A, 1999 185:539-550). By exploring the mechanisms, specializations and limitations of NO signaling this research will help to understand how groups of neurons work together to produce appropriate behaviors.

Firefly flashing and Nitric oxide

     In related research with collaborators in the Biology Department and at Harvard Medical school we have proposed that NO is a key controller for the initiation of firefly flashes. Although bioluminescent flashing is central to firefly reproduction, the specific molecular mechanisms involved in flash control remain a long-standing mystery. We found that. NO gas stimulates light production by fireflies, and NO scavengers block photogenic responses to the neurotransmitter octopamine. The enzyme NO synthase is robustly expressed in the firefly lantern. We have proposed that NO inhibits mitochondrial respiration within photocytes, transiently allowing oxygen access to organelles containing light-emitting compounds. Although NO is known to inhibit mitochondria this has not previously been recognized as a physiological site of action.

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