A review of the circuit-level and cellular mechanisms contributing to locomotor acceleration in the marine mollusk Clione limacina.

The pteropod mollusk, Clione limacina, is a useful model system for understanding the neural basis of behavior. Of particular interest are the unique swimming behavior and neural circuitry that underlies this swimming behavior. The swimming system of Clione has been studied by two primary groups-one in Russia and one in the United States of America-for more than four decades. The neural circuitry, the cellular properties, and ion channels that create and change the swimming locomotor rhythm of Clione-particularly mechanisms that contribute to swimming acceleration-are presented in this review.

Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons.

Both nitric oxide (NO) and serotonin (5HT) mediate swim acceleration in the marine mollusk, Clione  limacina. In this study, we examine the role that the second messenger, cyclic guanosine monophosphate (cGMP), plays in mediating NO and 5HT-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase (sGC) increased fictive locomotor speed recorded from Pd-7 interneurons of the animal's locomotor central pattern generator. Moreover, inhibition of sGC decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because NO has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by 5HT application, we hypothesize that both NO and 5HT function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates NO-induced but not 5HT-induced swim acceleration in Clione.

ZD7288 and mibefradil inhibit the myogenic heartbeat in Daphnia magna indicating its dependency on HCN and T-type calcium ion channels.

Daphnia magna heartbeat is myogenic-originating within the animal's heart. However, the mechanism for this myogenic automaticity is unknown. The mechanism underlying the automaticity of vertebrate myogenic hearts involves cells (pacemaker cells), which have a distinct set of ion channels that include hyperpolarization activated cyclic nucleotide-gated (HCN) and T-type calcium ion channels. We hypothesized that these ion channels also underlie the automatic myogenic heartbeat of Daphnia magna. The drugs, ZD7288 and mibefradil dihydrochloride, block HCN and T-type calcium ion channels respectively. Application of these drugs, in separate experiments, show that they inhibit the heartbeat of Daphnia magna in a dose-dependent manner. Calculation of the percent difference between the heart rate of pretreatment (before drug application) and heart rate following drug application (post-treatment) allowed us to graph a dose-response curve for both ZD7288 and mibefradil, revealing that ZD7288 produces a greater effect on decreasing heart rate. This indicates the HCN ion channels play a foremost role in generating Daphnia magna heartbeat. Our results show conclusively that HCN and T-type calcium ion channels underlie the automatic myogenic heartbeat in Daphnia magna-and suggest a conserved mechanism for generating myogenic heartbeat within the animal kingdom. Thus, Daphnia magna represents a credible model system for further exploration of cardiac physiology.

A hyperpolarization-activated inward current alters swim frequency of the pteropod mollusk Clione limacina.

The pteropod mollusk, Clione limacina, exhibits behaviorally relevant swim speed changes that occur within the context of the animal's ecology. Modulation of C. limacina swimming speed involves changes that occur at the network and cellular levels. Intracellular recordings from interneurons of the swim central pattern generator show the presence of a sag potential that is indicative of the hyperpolarization-activated inward current (I(h)). Here we provide evidence that I(h) in primary swim interneurons plays a role in C. limacina swimming speed control and may be a modulatory target. Recordings from central pattern generator swim interneurons show that hyperpolarizing current injection produces a sag potential that lasts for the duration of the hyperpolarization, a characteristic of cells possessing I(h). Following the hyperpolarizing current injection, swim interneurons also exhibit postinhibitory rebound (PIR). Serotonin enhances the sag potential of C. limacina swim interneurons while the I(h) blocker, ZD7288, reduces the sag potential. Furthermore, a negative correlation was found between the amplitude of the sag potential and latency to PIR. Because latency to PIR was previously shown to influence swimming speed, we hypothesize that I(h) has an effect on swimming speed. The I(h) blocker, ZD7288, suppresses swimming in C. limacina and inhibits serotonin-induced acceleration, evidence that supports our hypothesis.

The role of postinhibitory rebound in the locomotor central-pattern generator of Clione limacina.

In animals, networks of central neurons, called central-pattern generators (CPGs), produce a variety of locomotory behaviors including walking, swimming, and flying. CPGs from diverse animals share many common characteristics that function at the system level, circuit level, and cellular level. However, the relative roles of common CPG characteristics are variable among different animal species, in ways that suit different forms of locomotion in different environmental contexts. Here, we examine some of these common features within the locomotor CPG in a model system used to investigate changes in locomotory speed-the swim system of the pteropod mollusk, Clione limacina. In particular, we discuss the role of one cellular characteristic that is essential for locomotor pattern generation in Clione, postinhibitory rebound.

The contribution of the pleural type 12 interneuron to swim acceleration in Clione limacina.

The pteropod mollusc, Clione limacina, swims by alternate dorsal-ventral flapping movements of its wing-like parapodia. The basic swim rhythm is produced by a network of pedal swim interneurons that comprise a swim central pattern generator (CPG). Serotonergic modulation of both intrinsic cellular properties of the swim interneurons and network properties contribute to swim acceleration, the latter including recruitment of type 12 interneurons into the CPG. Here we address the role of the type 12 interneurons in swim acceleration. A single type 12 interneuron is found in each of the pleural ganglia, which contributes to fast swimming by exciting the dorsal swim interneurons while simultaneously inhibiting the ventral swim interneurons. Each type 12 interneuron sends a single process through the pleural-pedal connective that branches in both ipsilateral and contralateral pedal ganglia. This anatomical arrangement allowed us to manipulate the influence of the type 12 interneurons on the swim circuitry by cutting the pleural-pedal connective followed by a "culture" period of 48 h. The mean swim frequency of cut preparations was reduced by 19% when compared to the swim frequency of uncut preparations when stimulated with 10(-6) M serotonin; however, this decrease was not statistically significant. Additional evidence suggests that the type 12 interneurons may produce a short-term, immediate effect on swim acceleration while slower, modulatory inputs are taking shape.

Cellular Mechanisms Underlying Swim Acceleration in the Pteropod Mollusk Clione limacina.

The pteropod mollusk Clione limacina swims by dorsal-ventral flapping movements of its wing-like parapodia. Two basic swim speeds are observed-slow and fast. Serotonin enhances swimming speed by increasing the frequency of wing movements. It does this by modulating intrinsic properties of swim interneurons comprising the swim central pattern generator (CPG). Here we examine some of the ionic currents that mediate changes in the intrinsic properties of swim interneurons to increase swimming speed in Clione. Serotonin influences three intrinsic properties of swim interneurons during the transition from slow to fast swimming: baseline depolarization, postinhibitory rebound (PIR), and spike narrowing. Current clamp experiments suggest that neither I(h) nor I(A) exclusively accounts for the serotonin-induced baseline depolarization. However, I(h) and I(A) both have a strong influence on the timing of PIR-blocking I(h) increases the latency to PIR while blocking I(A) decreases the latency to PIR. Finally, apamin a blocker of I(K(Ca)) reverses serotonin-induced spike narrowing. These results suggest that serotonin may simultaneously enhance I(h) and I(K(Ca)) and suppress I(A) to contribute to increases in locomotor speed.