An identified central pattern‐generating neuron co‐ordinates sensory‐motor components of respiratory behavior in Lymnaea

Abstract

Defining the attributes of individual central pattern-generating (CPG) neurons underlying various rhythmic behaviors are fundamental to our understanding of how the brain controls motor programs, such as respiration and locomotion. To this end, we have explored a simple invertebrate preparation in which the neuronal basis of respiratory rhythmogenesis can be investigated from the whole animal to a single cell level. An identified dopaminergic neuron, termed right pedal dorsal 1 (RPeD1), is a component of the CPG network which controls hypoxia-driven, aerial respiration in the fresh water snail Lymnaea stagnalis. Using intact, semi-intact and isolated brain preparations, we have discovered that in addition to its role as a respiratory CPG neuron, RPeD1 co-ordinates sensory-motor input from the pneumostome (the respiratory orifice) at the water/air interface to initiate respiratory rhythm generation. An additional, novel role of RPeD1 was also found. Specifically, direct intracellular stimulation of RPeD1 induced pneumostome openings, in the absence of motor neuronal activity. To determine further the role of RPeD1 in the respiratory behavior of intact animals, either its axon was severed or the soma selectively killed. Many components of the respiratory behavior in the intact animals were found to be perturbed following RPeD1 axotomy or 'somatomy' (soma removed). Taken together, the data presented provide a direct demonstration that RPeD1 is a multifunctional CPG neuron, which also serves many additional roles in the control of breathing behavior, ranging from co-ordination of mechanosensory input to the motor control of the respiratory orifice.

Integrative biology of an embryonic respiratory behaviour in pond snails:the `embryo stir-bar hypothesis'

“…L. stagnalis has been used primarily to study the neural mechanisms underlying feeding and respiratory behaviours (Vavoulis et al, 2007;Bell et al, 2007;Haque et al, 2006), as well as a variety of questions on learning and memory (Martens et al, 2007), neural plasticity and cell biology (Dunn and Syed, 2006;Jimenez et al, 2006). While H. trivolvis has also contributed in some of these areas (Murphy, 2001;Torreano et al, 2005), it has become a particularly good model to address a broad range of developmental questions because of the advantageous morphological and biomechanical properties of its egg mass.…”

GABAA- and AMPA-like receptors modulate the activity of an identified neuron within the central pattern generator of the pond snail Lymnaea stagnalis

“…Such a preparation provides a valuable model system to elucidate the nature of ionotropic ion channels that shape the bio-electrical behavior of RPeD1. It has been shown that, in the isolated CNS, RPeD1 frequently exhibits a spontaneously occurring respiratory discharge, similar to that recorded in ''semiintact preparations'' following direct current injection or mechano-chemical stimulation of the neuron (Bell et al 2007;Haque et al 2006;Holden et al 1982;Inoue et al 1996Inoue et al , 2001McComb et al 2003). Such spontaneous activity depends on neurotransmitter release from yet to identify presynaptic terminals.…”

“…The onset of patterned respiratory activity is controlled by both excitatory and inhibitory inputs mainly conveyed to RPeD1 from the pneumostome area (Bell et al 2007;Haque et al 2006;Inoue et al 2001;Lukowiak et al 2006;McComb et al 2003). Strikingly, this behavior can undergo a dramatic operant conditioning and the resulting changes (i.e., associative learning) be consolidated into both intermediateand long-term memory McComb et al 2005;Spencer et al 2002).…”

“…The motor output generated by RPeD1 in the isolated ganglion appears as periodical bursts of action potentials which are driven by ligand-dependent ion channels operated by synapticallyreleased neurotransmitter(s) (Syed et al 1990;Taylor and Lukowiak 2000). RPeD1 may be considered as a multifunctional CPG interneuron : it not only establishes synaptic connections within the circuit to drive aerial respiration rhythmogenesis, but makes synaptic contacts with peripheral sensory and motor elements in the pneumostome area to adjust the breathing output according to the behavioral needs of the snail (Bell et al 2007;Haque et al 2006;Lukowiak et al 2003Lukowiak et al , 2006. Accordingly, RPeD1 does not initiate the fictive respiratory output (i.e., is quiescent) in the so-called ''semi-intact preparation'', where the CNS retains the innervation to (and perhaps from) the pneumostome area (Inoue et al 1996(Inoue et al , 2001.…”

“…The latter, in turn, convey an excitatory output to RPeD1 via a direct synaptic connection, which triggers the patterned rCPG activity and consequently, aerial respiration (Bell et al 2007;Inoue et al 2001). Furthermore, pneumostome opening at the saline (water)/air interface relays an additional excitatory outflow to RPeD1 (Haque et al 2006). Both in the isolated CNS and in ''semi-intact preparations'', the rhythm is maintained by IP3, which is the only other known central activator of RPeD1 and re-excites RPeD1 sufficiently to initiate further cycles of rCPG activity (Syed et al 1990;Lukowiak and Syed 1999).…”