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Biomedical subjects

J T Birmingham

Publications and source records attributed to J T Birmingham.

5 recordsLinked to original sources

GABA enhances transmission at an excitatory glutamatergic synapse.

GABA mediates both presynaptic and postsynaptic inhibition at many synapses. In contrast, we show that GABA enhances transmission at excitatory synapses between the lateral gastric and medial gastric motor neurons and the gastric mill 6a and 9 (gm6a, gm9) muscles and between the lateral pyloric motor neuron and pyloric 1 (p1) muscles in the stomach of the lobster Homarus americanus. Two-electrode current-clamp or voltage-clamp techniques were used to record from muscle fibers. The innervating nerves were stimulated to evoke excitatory junctional potentials (EJPs) or excitatory junctional currents. Bath application of GABA first decreased the amplitude of evoked EJPs in gm6a and gm9 muscles, but not the p1 muscle, by activating a postjunctional conductance increase that was blocked by picrotoxin. After longer GABA applications (5-15 min), the amplitudes of evoked EJPs increased in all three muscles. This increase persisted in the presence of picrotoxin. beta-(Aminomethyl)-4-chlorobenzenepropanoic acid (baclofen) was an effective agonist for the GABA-evoked enhancement but did not increase the postjunctional conductance. Muscimol activated a rapid postsynaptic conductance but did not enhance the amplitude of the nerve-evoked EJPs. GABA had no effect on iontophoretic responses to glutamate and decreased the coefficient of variation of nerve-evoked EJPs. In the presence or absence of tetrodotoxin, GABA increased the frequency but not the amplitude of miniature endplate potentials. These data suggest that GABA acts presynaptically via a GABA(B)-like receptor to increase the release of neurotransmitter.

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Increasing sensor flexibility through neuromodulation.

Both biological and man-made motor control networks require input from sensors to allow for modification of the motor program. Real sensory neurons are more flexible than typical robotic sensors because they are dynamic rather than static. The membrane properties of neurons and hence their excitability can be modified by the presence of neuromodulatory substances. In the case of a sensory neuron, this can change, in a functionally significant way, the code used to describe a stimulus. For instance, extension of the neuron's dynamic range or modification of its filtering characteristics can result. This flexibility has an apparent cost. The code used may be situation-dependent and hence difficult to interpret. To address this issue and to understand how neuromodulation is used effectively in a motor control network, I am studying the GPR2 stretch receptor in the crustacean stomatogastric nervous system. Several different neuromodulatory substances can modify its encoding properties. Comparisons of physiological and anatomical evidence suggest that neuromodulation can be effected both by GPR2 itself and by other neurons in the network. These results suggest that the analog of neuromodulation might be useful for improving sensor performance in an artificial motor control system.

Animals↗

Crab stomach pyloric muscles display not only excitatory but inhibitory and neuromodulatory nerve terminals.

Movements of the foregut in crustaceans are produced by striated muscles that are innervated by motor neurons in the stomatogastric ganglion (STG). Firing of the STG motor neurons generates excitatory junctional potentials (EJPs) in the stomach muscles. We now provide evidence for the existence of separate inhibitory and neuromodulatory innervations of some pyloric muscles in the foregut of several crabs, Callinectes sapidus, Cancer magister, and Cancer borealis. Electron microscopic examination of several pyloric muscles revealed three distinct types of nerve terminals. Excitatory terminals were readily identified by the spherical shape of their small, clear synaptic vesicles. These terminals also housed a few large dense core vesicles. Inhibitory nerve terminals were recognized by the elliptical shape of their small, clear synaptic vesicles, and contacted the muscles at well-defined synapses equipped with dense bar active zones. Bath application of GABA reduced the amplitudes of EJPs in a pyloric muscle of C. borealis, consistent with the presence of GABAergic inhibitory innervation. Neuromodulatory terminals were characterized by their predominant population of large dense and dense core vesicles. These terminals formed synapses with presynaptic dense bars on the muscle, as well as on the excitatory and inhibitory nerve terminals. The presence of the inhibitory and neuromodulatory terminals creates a functional context for previously described reports of neuromodulatory actions on stomach muscles and suggests that the transfer function from STG motor patterns to pyloric movement may be orchestrated by a complex innervation from sources outside of the STG itself.

Animals↗

Encoding of muscle movement on two time scales by a sensory neuron that switches between spiking and bursting modes.

The gastropyloric receptor (GPR) neurons of the stomatogastric nervous system of the crab Cancer borealis are muscle stretch receptors that can fire in either a spiking or a bursting mode of operation. Our goal is to understand what features of muscle stretch are encoded by these two modes of activity. To this end, we characterized the responses of the GPR neurons in both states to sustained and rapidly varying imposed stretches. The firing rates of spiking GPR neurons in response to rapidly varying stretches were directly related to stretch amplitude. For persistent stretches, spiking-mode firing rates showed marked adaptation indicating a more complex relationship. Interspike intervals of action potentials fired by GPR neurons in the spiking mode were used to construct an accurate estimate of the time-dependent amplitude of stretches in the frequency range of the gastric mill rhythm (0.05-0.2 Hz). Spike trains arising from faster stretches (similar to those of the pyloric rhythm) were decoded using a linear filter to construct an estimate of stretch amplitude. GPR neurons firing in the bursting mode were relatively unaffected by rapidly varying stretches. However, the burst rate was related to the amplitude of long, sustained stretches, and very slowly varying stretches could be reconstructed from burst intervals. In conclusion, the existence of spiking and bursting modes allows a single neuron to encode both rapidly and slowly varying stimuli and thus to report cycle-by-cycle muscle movements as well as average levels of muscle tension.

Action Potentials↗

Temporal dynamics of convergent modulation at a crustacean neuromuscular junction.

At least 10 different substances modulate the amplitude of nerve-evoked contractions of the gastric mill 4 (gm4) muscle of the crab, Cancer borealis. Serotonin, dopamine, octopamine, proctolin, red pigment concentrating hormone, crustacean cardioactive peptide, TNRNFLRFamide, and SDRNFLRFamide increased and -allatostatin-3 and histamine decreased the amplitude of nerve-evoked contractions. Modulator efficacy was frequency dependent; TNRNFLRFamide, proctolin, and allatostatin-3 were more effective when the motor neuron was stimulated at 10 Hz than at 40 Hz, whereas the reverse was true for dopamine and serotonin. The modulators that were most effective at high stimulus frequencies produced a significant decrease in muscle relaxation time; those that were most effective at low stimulus frequencies produced modest increases in relaxation time. Thus modulator actions that appear redundant when examined only at one stimulus frequency are differentiated when a range of stimulus dynamics is studied. The effects of TNRNFLRFamide, serotonin, proctolin, dopamine, and -allatostatin-3 on the amplitude and facilitation of nerve-evoked excitatory junctional potentials (EJPs) in the gm4 and gastric mill 6 (gm6) muscles were compared. The EJPs in gm4 have a large initial amplitude and show relatively little facilitation, whereas the EJPs in gm6 have a small initial amplitude and show considerable facilitation. Modulators that enhanced contractions also enhanced EJP amplitude; -allatostatin-3 reduced EJP amplitude. The effects of these modulators on EJP amplitude were modest and showed no significant frequency dependence. This suggests that the frequency dependence of modulator action on contraction results from effects on excitation-contraction coupling. The modulators affected facilitation at these junctions in a manner consistent with a change in release probability. They produced a change in facilitation that is inversely related to their action on EJP amplitude.

Animals↗