Reliable, Responsive Pacemaking and Pattern Generation With Minimal Cell Numbers: the Crustacean Cardiac Ganglion

Abstract

Investigations of the electrophysiology of crustacean cardiac ganglia over the last half-century are reviewed for their contributions to elucidating the cellular mechanisms and interactions by which a small (as few as nine cells) neuronal network accomplishes extremely reliable, rhythmical, patterned activation of muscular activity-in this case, beating of the neurogenic heart. This ganglion is thus a model for pacemaking and central pattern generation. Favorable anatomy has permitted voltage- and space-clamp analyses of voltage-dependent ionic currents that endow each neuron with the intrinsic ability to respond with rhythmical, patterned impulse activity to nonpatterned stimulation. The crustacean soma and initial axon segment do not support impulse generation but integrate input from stretch-sensitive dendrites and electrotonic and chemically mediated synapses on axonal processes in neuropils. The soma and initial axon produce a depolarization-activated, calcium-mediated, sustained potential, the "driver potential," so-called because it drives a train of impulses at the "trigger zone" of the axon. Extreme reliability results from redundancy and the electrotonic coupling and synaptic interaction among all the neurons. Complex modulation by central nervous system inputs and by neurohormones to adjust heart pumping to physiological demands has long been demonstrated, but much remains to be learned about the cellular and molecular mechanisms of action. The continuing relevance of the crustacean cardiac ganglion as a relatively simple model for pacemaking and central pattern generation is confirmed by the rapidly widening documentation of intrinsic potentials such as plateau potentials in neurons of all major animal groups. The suite of ionic currents (a slowly inactivating calcium current and various potassium currents, with variations) observed for the crustacean cardiac ganglion have been implicated in or proven to underlie a majority of the intrinsic potentials of neurons involved in pattern generation.

Nitric Oxide Inhibits the Rate and Strength of Cardiac Contractions in the LobsterHomarus americanusby Acting on the Cardiac Ganglion

“…For these experiments, a small hole was cut in the ventral heart muscle wall and the ganglionic trunk was cut at the level of the posterior lateral nerves (Cooke, 2002). A suction electrode was introduced through this hole and the anterior portion of the ganglion, containing most of the motor neurons, was sucked up and stimulated with bursts.…”

“…The cardiac ganglion generates the rhythmic motor pattern that drives lobster heart contractions, and lobster cardiac muscle has no myogenic contraction (Cooke, 2002). Therefore, any SNAPinduced change in contraction frequency of the heart must be caused by changes in the firing patterns of the motor neurons found in the cardiac ganglion.…”

“…Indeed, NO is known to trigger a biochemical response (increased cGMP metabolism) when applied to the isolated cardiac ganglion of the crab (Scholz et al, 2002). Because the function of the cardiac ganglion is to provide the synaptic input that drives the contractions of the heart (Alexandrowicz, 1932;Cooke, 2002), it is attractive to speculate that NO may provide feedback information about the status of cardiac muscle that could be used to modulate the activity of the ganglion. A conceptually similar retrograde signaling role has been described for NO at a number of synapses in the vertebrate CNS (Daniel et al, 1993;Boulton et al, 1995;Arancio et al, 1996;Boxall and Garthwaite, 1996;Lev-Ram et al, 1997;Prast and Philippu, 2001).…”

Modulation of an Integrated Central Pattern Generator–Effector System: Dopaminergic Regulation of Cardiac Activity in the Blue CrabCallinectes sapidus

“…Direct modulation of the posterior motor neurons cannot be excluded, however, because their synaptic input and impulse initiation occur in the anterior portion of the ganglion, in a region that receives substantial THli innervation ( Fig. 7A; see Cooke 2002;Mirolli et al 1987;Tazaki and Cooke 1983a). It is also notable that the THli projections are confined to the ganglion itself.…”

“…The heartbeat in marine species is driven by a simple (usually 9 neurons) central pattern generating circuit, the cardiac ganglion (CG), positioned within the dorsal wall of the heart (Cooke 1988(Cooke , 2002. The CG is directly controlled by a small number of modulatory fibers that originate in the CNS (Delgado et al 2000;Field and Larimer 1975;Maynard 1960;Yazawa and Kuwasawa 1994).…”