G Protein Signaling in a Neuronal Network is Necessary for Rhythmic Motor Pattern Production

Abstract

Clemens, Stefan, and Paul S. Katz. G protein signaling in a neuronal network is necessary for rhythmic motor pattern production. J Neurophysiol 89: 762-772, 2003; 10.1152/jn.00765.2002. G protein-coupled receptors are widely recognized as playing important roles in mediating the actions of extrinsic neuromodulatory inputs to motor networks. However, the potential for their direct involvement in rhythmic motor pattern generation has received considerably less attention. Results from this study indicate that G protein signaling appears to be integral to the operation of the central pattern generator (CPG) underlying the escape swim of the mollusk Tritonia diomedea. Blocking G protein signaling in a single CPG neuron, cerebral neuron C2, with intracellular iontophoresis of the guanine nucleotide analogue guanosine 5Ј-O-(2-thiodiphosphate) (GDP-␤-S), prevented the production of the swim motor program. Moreover, tonic activation of G protein signaling in this neuron by iontophoresis of the GTP analogues guanosine 5Ј-O-(3-thiotriphosphate) (GTP-␥-S) and 5Ј-guanylyl-imidodiphosphate also inhibited motor pattern production. The possible sites of action of these guanine nucleotide analogues were examined to assess potential mechanisms by which they interfered with motor pattern production. Intracellular iontophoresis of GDP-␤-S into C2 did not affect C2 basal synaptic strength. However, it did reduce heterosynaptic facilitation of C2 synapses caused by the dorsal swim interneurons (DSIs), a set of serotonergic swim CPG neurons. In contrast, GTP-␥-S directly enhanced C2 synaptic strength onto DFN, mimicking the neuromodulatory effect of the DSIs. GDP-␤-S, but not the GTP analogues, decreased C2 excitability, whereas both GTP analogues, but not GDP-␤-S, blocked the ability of DSI stimulation to increase C2 excitability. The decrease in C2 excitability caused by GDP-␤-S is not likely to be responsible for the inhibition of the swim motor pattern because decreasing C2 firing rate, by injecting hyperpolarizing current, did not prevent the production of the rhythmic motor pattern. Taken together, these data suggest that G protein signaling is a necessary and integral component of the escape swim CPG in Tritonia and that G protein signaling mediates DSI heterosynaptic facilitation of C2 but may not mediate the DSI-evoked enhancement of C2 excitability.

Spike Timing-Dependent Serotonergic Neuromodulation of Synaptic Strength Intrinsic to a Central Pattern Generator Circuit

“…10) is consistent with a presynaptic locus, because low-output synapses tend to facilitate more than high-output synapses (Zucker and Regehr, 2002). A presynaptic site of action is also consistent with previous results that showed DSI increasing neurotransmitter release from the other CPG neuron, C2 (Katz and Frost, 1995b;Clemens and Katz, 2003); however, these results do not rule out the possibility of changes in the sensitivity of the postsynaptic receptors in VFN. A similar change in sensitivity of AMPA receptors has been shown to play a role in modulating inspiratory drive to hypoglossal motor neurons (Bocchiaro et al, 2003).…”

Mechanisms contributing to the dopamine induction of crawl-like bursting in leech motoneurons

“…It has been previously reported that DA causes a statistically significant increase in the peak amplitude of the PIR in DE-3, but not the area under the curve (Vallecorsa et al, 2007). An increase in overall cellular excitability is one way that neuromodulators can exert their influence over CPG activation (Clemens and Katz, 2003;Dai et al, 1998;Fedirchuk and Dai, 2004;Katz, 1998;Katz and Frost, 1997). Based on firing frequency, as an indicator of cell excitability, we found that DA reduced neuronal excitability, but only in the context of current injection.…”

Role of Membrane Potential in Calcium Signaling During Rhythmic Bursting in Tritonia Swim Interneurons

“…Further, activation of metabotropic receptors can lead to an augmentation of Ca 2ϩ -induced Ca 2ϩ release from internal stores. In lamprey reticulospinal axons, activation of metabotropic glutamate receptors leads to a rapid release of Ca 2ϩ from intracellular stores in a Ca 2ϩ -dependent manner (Cochilla and Alford 1998). These Ca 2ϩ signals would not be reproduced by the voltage signal alone in the absence of the synaptic inputs that triggered the second-messenger cascade that produced or augmented the Ca 2ϩ signals.…”

“…The VSI result was somewhat unexpected; we hypothesized that neuromodulatory or synaptically driven Ca 2ϩ signals would contribute to the Ca 2ϩ signal recorded during the SMP. Dynamic biochemical signaling has been speculated to play a potentially integral role in the generation of the Tritonia SMP (Clemens and Katz 2003). Therefore we expected that VSI would receive at least some synaptic inputs during an SMP that would have produced some of the SMP Ca 2ϩ signal.…”