A common modular design of nervous systems originating in soft-bodied invertebrates.

Nervous systems of vertebrates and invertebrates show a common modular theme in the flow of information for cost-benefit decisions. Sensory inputs are incentivized by integrating stimulus qualities with motivation and memory to affect appetitive state, a system of homeostatic drives, and labelled for directionality. Appetitive state determines action responses from a repertory of possibles and transmits the decision to a premotor system that frames the selected action in motor arousal and appropriate postural and locomotion commands. These commands are then sent to the primary motor pattern generators controlling the motorneurons, with feedback at each stage. In the vertebrates, these stages are mediated by forebrain pallial derivatives for incentive and directionality (olfactory bulb, cerebral cortex, pallial amygdala, etc.) interacting with hypothalamus (homeostasis, motivation, and reward) for action selection in the forebrain basal ganglia, the mid/hindbrain reticular formation as a premotor translator for posture, locomotion, and arousal state, and the spinal cord and cranial nuclei as primary motor pattern generators. Gastropods, like the predatory sea slug Pleurobranchaea californica, show a similar organization but with differences that suggest how complex brains evolved from an ancestral soft-bodied bilaterian along with segmentation, jointed skeletons, and complex exteroceptors. Their premotor feeding network combines functions of hypothalamus and basal ganglia for homeostasis, motivation, presumed reward, and action selection for stimulus approach or avoidance. In Pleurobranchaea, the premotor analogy to the vertebrate reticular formation is the bilateral "A-cluster" of cerebral ganglion neurons that controls posture, locomotion, and serotonergic motor arousal. The A-cluster transmits motor commands to the pedal ganglia analogs of the spinal cord, for primary patterned motor output. Apparent pallial precursors are not immediately evident in Pleurobranchaea's central nervous system, but a notable candidate is a subepithelial nerve net in the peripheral head region that integrates chemotactile stimuli for incentive and directionality. Evolutionary centralization of its computational functions may have led to the olfaction-derived pallial forebrain in the ancestor's vertebrate descendants and their analogs in arthropods and annelids.

Coordination of Locomotion by Serotonergic Neurons in the Predatory Gastropod Pleurobranchaea californica.

Similar design characterizes neuronal networks for goal-directed motor control across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Evidence is lacking for whether this design evolved independently in those lineages, evolved in parallel with segmentation and appendages, or could have been present in a soft-bodied common ancestor. We examined coordination of locomotion in an unsegmented, ciliolocomoting gastropod, the sea slug Pleurobranchaea californica, which may better resemble the urbilaterian ancestor. Previously, bilateral A-cluster neurons in cerebral ganglion lobes were found to compose a multifunctional premotor network controlling the escape swim and feeding suppression, and mediating action selection for approach or avoidance turns. Serotonergic As interneurons of this cluster were critical elements for swimming, turning, and behavioral arousal. Here, known functions were extended to show that the As2/3 cells of the As group drove crawling locomotion via descending signals to pedal ganglia effector networks for ciliolocomotion and were inhibited during fictive feeding and withdrawal. Crawling was suppressed in aversive turns, defensive withdrawal, and active feeding, but not during stimulus-approach turns or prebite proboscis extension. Ciliary beating was not inhibited during escape swimming. These results show how locomotion is adaptively coordinated in tracking, handling, and consuming resources, and in defense. Taken with previous results, they also show that the A-cluster network acts similarly to the vertebrate reticular formation with its serotonergic raphe nuclei in facilitating locomotion, postural movements, and motor arousal. Thus, the general scheme controlling locomotion and posture might well have preceded the evolution of segmented bodies and articulated appendages.SIGNIFICANCE STATEMENT Similar design in the neuronal networks for goal-directed motor control is seen across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Whether that design evolved independently or in parallel with complexity in body and behavior has been unanswered. Here it is shown that a simple sea slug, with primitive ciliary locomotion and lacking segmentation and appendages, has similar modular design in network coordination as vertebrates for posture in directional turns and withdrawal, locomotion, and general arousal. This suggests that a general neuroanatomical framework for the control of locomotion and posture could have arisen early during the evolution of bilaterians.

Comparative Analysis of Neuropeptides in Homologous Interneurons and Prohormone Annotation in Nudipleuran Sea Slugs.

Despite substantial research on neuronal circuits in nudipleuran gastropods, few peptides have been implicated in nudipleuran behavior. In this study, we expanded the understanding of peptides in this clade, using three species with well-studied nervous systems, Hermissenda crassicornis, Melibe leonina, and Pleurobranchaea californica. For each species, we performed sequence homology analysis of de novo transcriptome predictions to identify homologs to 34 of 36 prohormones previously characterized in the gastropods Aplysia californica and Lymnaea stagnalis. We then used single-cell mass spectrometry to characterize peptide profiles in homologous feeding interneurons: the multifunctional ventral white cell (VWC) in P. californica and the small cardioactive peptide B large buccal (SLB) cells in H. crassicornis and M. leonina. The neurons produced overlapping, but not identical, peptide profiles. The H. crassicornis SLB cells expressed peptides from homologs to the FMRFamide (FMRFa), small cardioactive peptide (SCP), LFRFamide (LFRFa), and feeding circuit activating peptides prohormones. The M. leonina SLB cells expressed peptides from homologs to the FMRFa, SCP, LFRFa, and MIP-related peptides prohormones. The VWC, previously shown to express peptides from the FMRFa and QNFLa (a homolog of A. californica pedal peptide 4) prohormones, was shown to also contain SCP peptides. Thus, each neuron expressed peptides from the FMRFa and SCP families, the H. crassicornis and M. leonina SLB cells expressed peptides from the LFRFa family, and each neuron contained peptides from a prohormone not found in the others. These data suggest each neuron performs complex co-transmission, which potentially facilitates a multifunctional role in feeding. Additionally, the unique feeding characteristics of each species may relate, in part, to differences in the peptide profiles of these neurons. These data add chemical insight to enhance our understanding of the neuronal basis of behavior in nudipleurans and other gastropods.