Crustacean motor neurons subserving locomotion are specialized for the type of activity in which they normally participate. Neurons responsible for maintained activity (‘tonic’ neurons) support moderate to high frequencies of nerve impulses intermittently or continuously during locomotion, while those recruited for short-lasting rapid responses (‘phasic’ neurons) generally fire a few impulses in a rapid burst during rapid locomotion and are otherwise silent. The synaptic responses of the two types, recorded at their respective neuromuscular junctions, differ enormously: phasic neurons exhibit much higher quantal release per synapse and per muscle fibre, along with more rapid synaptic depression and less short-term facilitation. We have analyzed the factors that are responsible for the large difference in initial release of neurotransmitter. Several possibilities, including synapse and active zone size differences, entry of calcium at active zones, and immediately releasable vesicle pools, could not account for the large phasic-tonic difference in initial transmitter output. The most likely feature that differentiates synaptic release is the sensitivity of the exocytotic machinery to intracellular calcium. Molecular features of the phasic and tonic presynaptic nerve terminals are currently under investigation.

Environmental stresses such as high temperature or low levels of oxygen can lead to structural destabilization of cells, disruption of cellular processes, and, in extreme cases, death. Previous experience of sub-lethal stress can lead to protection during a subsequent stress that may otherwise have been lethal. Synapses are particularly vulnerable to extreme environmental conditions and failure of function at this level may be the primary cause of organismal death. Prior heat shock induces enhanced thermotolerance at neuromuscular junctions in the locust extensor tibiae muscle and in abdominal muscles of larval Drosophila. Synaptic thermoprotection is associated with an increase in short-term plasticity at these synapses. Prior anoxic coma in locusts induces synaptic thermotolerance suggesting that the same protective pathways are activated. It is well established that diverse forms of stress induce the upregulation of cellular chaperones (heat shock proteins; HSPs) that mediate acquired protection. The mechanisms underlying HSP-mediated synaptic protection are currently unknown but evidence is accumulating that stabilization of the cytoskeleton may play an important role.

Many organisms are exposed to harsh environmental conditions that may impair the operation of vital neuronal circuits and imperil the animal before these conditions directly cause cell and tissue death. Prior exposure to extreme but sub-lethal stress has long-term effects on neural circuit function enabling motor pattern generators to operate under previously non-permissive conditions. Using several model systems we have been investigating the mechanisms underlying stress-mediated neuroprotection, particularly thermotolerance imparted by a prior heat shock. Prior anoxia and cold shock also impart thermotolerance of motor pattern generation suggesting that different stressors activate common protective pathways. Synaptic transmission, action potential generation and neuronal potassium conductance are modulated by prior heat shock. Pharmacological block of potassium channels, which increases the duration of action potentials and the amplitude of postsynaptic potentials, mimics the thermoprotective effect of a prior heat shock. A universal consequence of heat shock and other stresses is the increased expression of a suite of heat shock proteins of which HSP70 is most closely linked to organismal thermotolerance. Increased levels of HSP70 are sufficient, but not necessary for synaptic thermoprotection. Accumulating evidence suggests the existence of multiple, overlapping pathways for protection and that these mechanisms may be neuron specific depending on their functional roles.

Despite an immense amount of variation in organisms throughout the animal kingdom many of their genes show substantial conservation in DNA sequence and protein function. Here we explore the potential for a conserved evolutionary relationship between genes and their behavioural phenotypes. We investigate the evolutionary history of cGMP-dependent protein kinase (PKG) and its possible conserved function in food-related behaviours. First identified for its role in the foraging behaviour of fruit flies, the PKG encoded by the foraging gene has since been associated with the maturation of behaviour (from nurse to forager) in honey bees and the roaming and dwelling food-related locomotion in nematodes. These parallels encouraged us to construct protein phylogenies using 32 PKG sequences that include 19 species. Our analyses suggest five possible evolutionary histories that can explain the apparent conserved link between PKG and behaviour in fruit flies, honey bees and nematodes. Three of these raise the hypothesis that PKG influences the food-related behaviours of a wide variety of animals including vertebrates. Moreover, it appears that the PKG gene was duplicated some time between the evolution of nematodes and a common ancestor of vertebrates and insects whereby current evidence suggests only the for-like PKG might be associated with food-related behaviour.

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.

Attempts to understand the neural mechanisms which produce behaviour must consider both prevailing sensory cues and the central cellular and synaptic changes they direct. At each level, neuromodulation can additionally shape the final output. We have investigated neuromodulation in the developing spinal motor networks in hatchling tadpoles of two closely related amphibians, Xenopus laevis and Rana temporaria to examine the subtle differences in their behaviours that could be attributed to their evolutionary divergence.

At the point of hatching, both species can swim in response to a mechanosensory stimulus, however Rana embryos often display a more forceful, non-locomotory coiling behaviour. Whilst the synaptic drive that underlies these behaviours appears similar, subtle inter-specific differences in neuronal properties shape motor outputs in different ways. For example, Rana neurons express N-methyl-D-aspartate (NMDA)/serotonin (5-HT)-dependent oscillations, not present in hatchling Xenopus and many also exhibit a prominent slow spike after-hyperpolarisation. Such properties may endow the spinal circuitry of Rana with the ability to produce a more flexible range of outputs.

Finally, we compare the roles of the neuromodulators 5-HT, noradrenaline (NA) and nitric oxide (NO) in shaping motor outputs. 5-HT increases burst durations during swimming in both Xenopus and Rana, but 5-HT dramatically slows the cycle period in Rana with little effect in Xenopus. Three distinct, but presumably homologous NO-containing brainstem clusters of neurons have been described, yet the effects of NO differ between species. In Xenopus, NO slows and shortens swimming in a manner similar to NA, yet in Rana NO and NA elicit the non-rhythmic coiling pattern.

Optical and genetic tools are beginning to revolutionize the studies of neuronal circuits. Neurons can now be labeled with conventional or genetically encoded indicators that allow their activity to be monitored during behavior in intact animals. Laser ablations and genetic inactivation offer ways to perturb activity of specific cells to test their contributions to behavior. These approaches promise to speed progress in the understanding of vertebrate networks in genetic model systems such as mice and zebrafish. Here we review some of the progress in applying these tools, with an emphasis on our work to develop and apply these approaches in the zebrafish model.

This paper reviews some aspects of locomotor plasticity after spinalisation and after peripheral nerve lesions. Adult cats can recover spontaneous hindlimb locomotion on a treadmill several days or weeks after a complete section of the spinal cord at T13. The kinematics as well as the electromyographic activity are compared in the same animal before and after the spinal section to highlight the resemblance of locomotor characteristics in the two conditions. To study further the mechanisms of spinal plasticity potentially underlying such locomotor recovery, we also summarize the locomotor adaptation of cats submitted to various types of peripheral nerve section of either ankle flexor or extensor muscles or after denervation of the hindpaws' cutaneous inputs. It is argued that, even in the spinal state, cats have the ability to compensate for such lesions of the peripheral nervous system suggesting that the spinal cord has a significant potential for adaptive plasticity that could be used in rehabilitation strategies to restore locomotion after spinal cord injury.