Neuromodulation of Neuronal Circuits: Back to the Future

Studies of the stomatogastric nervous systems of lobsters and crabs have led to numerous insights into the cellular and circuit mechanisms that generate rhythmic motor patterns. The small number of easily identifiable neurons allowed the establishment of connectivity diagrams among the neurons of the stomatogastric ganglion. We now know that (a) neuromodulatory substances reconfigure circuit dynamics by altering synaptic strength and voltage-dependent conductances and (b) individual neurons can switch among different functional circuits. Computational and experimental studies of single-neuron and network homeostatic regulation have provided insight into compensatory mechanisms that can underlie stable network performance. Many of the observations first made using the stomatogastric nervous system can be generalized to other invertebrate and vertebrate circuits.

Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs.

Glutamate-gated Chloride Channels

Publisher Summary Insects have provided material well suited to the investigation of CNS acetylcholine receptors. The central nervous tissues of these organisms have proved amenable to both radiolabelled- ligand-binding studies and single-cell electrophysiology of identifiable neurones. Binding studies have resulted in the characterization in vitro of three putative acetylcholine recognition sites each with a distinct pharmacological specificity. Of these three putative acetylcholine receptors defined biochemically, the α-bungarotoxin-sensitive receptor has been investigated the most. Pharmacological differences have emerged between this insect receptor and the nicotinic receptor of vertebrate muscle and electroplax tissue. The insect receptor is, for example, much less sensitive to decamethonium and carbamylcholine. Also the receptors mediating cercal-afferent, giantinterneurone synaptic transmission are much more sensitive to α-bungarotoxin and less sensitive to hexamethonium than the nicotinic receptors of vertebrate autonomic ganglia. Two other putative insect acetylcholine receptors both of which are insensitive to α-bungarotoxin have been investigated by radiolabelled-ligand binding methods. Insect material is particularly well suited for developmental and genetic approaches to receptor biology. Genetic studies offer another approach to the study of receptor biology for which insect material is supremely well suited. Hereditary changes in acetylcholine receptor structure have been reported in nicotine-resistant strains of Drosophila melanogaster.

Acetylcholine Receptors of Insects

1. The pyloric dilator (PD) and anterior burster (AB) neurons in the pyloric system of the lobster stomatogastric ganglion are electrically coupled and synchronously active. We have used the lucife...

Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. III. Synaptic connections of electrically coupled pyloric neurons

1. A study was performed of the L-glutamate, gamma-aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L-glutamate revealed three classes of responses: a K+-dependent inhibition which reversed at 15-20 mV more negative than the resting potential; a Cl- dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl- conductance, and a depolarizing response. 4. Picrotoxin (10(-6)-10(-5) M) was effective in blocking both the glutamate inhibitory responses. 10(-4) M-picrotoxin, which was necessary to produce a 50% block of the GABA-K+-dependent response, had no effect on the GABA-Cl- response. 5. beta-Guanidinopropionic acid (beta-GP) was found to be an agonist for the GABA-K+ response, but was ineffective in mimicking or blocking the GABA-Cl- response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl-beta-methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from -40 to -100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed.

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The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses.

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The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses.