Neuronal Control of Swimming Behavior: Comparison of Vertebrate and Invertebrate Model Systems

Swimming movements in the leech and lamprey are highly analogous, and lack homology. Thus, similarities in mechanisms must arise from convergent evolution rather than from common ancestry. Despite over 40 years of parallel investigations into this annelid and primitive vertebrate, a close comparison of the approaches and results of this research is lacking. The present review evaluates the neural mechanisms underlying swimming in these two animals and describes the many similarities that provide intriguing examples of convergent evolution. Specifically, we discuss swim initiation, maintenance and termination, isolated nervous system preparations, neural-circuitry, central oscillators, intersegmental coupling, phase lags, cycle periods and sensory feedback. Comparative studies between species highlight mechanisms that optimize behavior and allow us a broader understanding of nervous system function

Psychoneural reduction: a perspective from neural circuits

Abstract: Psychoneural reduction has been debated extensively in the philosophy of neuroscience. In this article I will evaluate metascientific approaches that claim direct molecular and cellular explanations of cognitive functions. I will initially consider the issues involved in linking cellular properties to behaviour from the general perspective of neural circuits. These circuits that integrate the molecular and cellular components underlying cognition and behaviour, making consideration of circuit properties relevant to reductionist debates. I will then apply this general perspective to specific systems where psychoneural reduction has been claimed, namely hippocampal long-term potentiation and the Aplysia gill-withdrawal reflex

The development and neuromodulation of motor control systems in pro-metamorphic Xenopus laevis frog tadpoles

My thesis has accomplished 3 significant contributions to neuroscience. Firstly, I have discovered a novel example of vertebrate deep-brain photoreception. Spontaneously generated fictive locomotion from the isolated nervous system of pro-metamorphic Xenopus tadpoles is sensitive to the ambient light conditions, despite input from the classical photoreceptive tissues of the retina and pineal complex being absent. The photosensitivity is found to be tuned to short wavelength UV light and is localised to a small region of the caudal diencephalon. Within this region, I have discovered a population of neurons immuno-positive for a UV-specific opsin protein, suggesting they are the means of phototransduction. This may be a hitherto overlooked mechanism linking environmental luminance to motor behaviour. Secondly, I have advanced the collective knowledge of how both nitric oxide and dopamine contribute to neuromodulation within motor control systems. Nitric oxide is shown to have an excitatory effect on the occurrence of spontaneous locomotor activity, representing a switch in its role from earlier in Xenopus development. Moreover, this excitatory effect is found to be mediated in the brainstem despite nitric oxide being shown to depolarise spinal neurons. Thirdly, I have developed a new preparation for patch-clamp recording in pro-metamorphic Xenopus tadpoles. My data suggest there are several changes to the cellular properties of neurons in the older animals compared with the embryonic tadpole; there appears to be an addition of Ih and K[sub](Ca) channels and the presence of tonically active and intrinsically rhythmogenic neurons. In addition, I have shown that at low doses dopamine acts via D2-like to hyperpolarise the membrane potential of spinal neurons, while at higher doses dopamine depolarises spinal neurons. These initial data corroborate previously reported evidence that dopamine has opposing effects on motor output via differential activation of dopamine receptor subtypes in Xenopus tadpoles

Initiation and maintenance of swimming in hatchling xenopus laevis tadpoles

Effective movement is central to survival and it is essential for all animals to react in response to changes around them. In many animals the rhythmic signals that drive locomotion are generated intrinsically by small networks of neurons in the nervous system which can be switched on and off. In this thesis I use a very simple animal, in which the behaviours and neuronal networks have been well characterised experimentally, to explore the salient features of such networks. Two days after hatching, tadpoles of the frog Xenopus laevis respond to a brief touch to the head by starting to swim. The swimming rhythm is driven by a small population of electrically coupled brainstem neurons (called dINs) on each side of the tadpole. These neurons also receive synaptic input following head skin stimulation. I build biophysical computational models of these neurons based on experimental data in order to address questions about the effects of electrical coupling, synaptic feedback excitation and initiation pathways. My aim is better understanding of how swimming activity is initiated and sustained in the tadpole. I find that the electrical coupling between the dINs causes their firing properties to be modulated. This allows two experimental observations to be reconciled: that a dIN only fires a single action potential in response to step current injections but the population fires like pacemakers during swimming. I build on this hypothesis and show that long-lasting, excitatory feedback within the population of dINs allows rhythmic pacemaker activity to be sustained in one side of the nervous system. This activity can be switched on and off at short latency in response to biologically realistic synaptic input. I further investigate models of synaptic input from a defined swim initiation pathway and show that electrical coupling causes a population of dINs to be recruited to fire either as a group or not at all. This allows the animal to convert continuously varying sensory stimuli into a discrete decision. Finally I find that it is difficult to reliably start swimming-like activity in the tadpole model using simple, short-latency, symmetrical initiation pathways but that by using more complex, asymmetrical, neuronal-pathways to each side of the body, consistent with experimental observations, the initiation of swimming is more robust. Throughout this work, I make testable predictions about the population of brainstem neurons and also describe where more experimental data is needed. In order to manage the parameters and simulations, I present prototype libraries to build and manage these biophysical model networks

Recurrent excitation and inhibition in the Renshaw cell-motoneuron circuit of the lumbar spinal cord

Motor output from spinal motoneurons is influenced by interneuron networks in the ventral horn of the spinal cord. This thesis presents electrophysiologi- cal investigations of two separate but complementary aspects of the neuronal networks that influence this motor output. The first investigation focuses on inhibition of lumbar motoneurons. The second characterises the excitatory synapse formed by motoneuron axon collaterals onto Renshaw cells, which are interneurons that mediate recurrent inhibition onto motoneurons. Previous studies on neonatal rats have shown that inhibition of motoneu- rons is mediated a mixed GABAergic and glycinergic response. Whole- cell voltage-clamp recordings of spinal motoneurons obtained from juvenile (P 8 − 14) mice demonstrated that motoneuron inhibition is mostly mediated by glycine. GABA currents were not co-detected with glycine during this age range in the mouse. Further experiments, in which the relative content of pre-synaptic GABA and glycine was manipulated, showed that GABA is not co-released with glycine by premotor interneurons. Quantal analysis of paired recordings of pre-synaptic motoneurons and post-synaptic Renshaw cells showed that this excitatory synapse exhibits a large number of release sites and a high probability of release. This is suggestive of highly reliable synaptic transmission between the two cell types. Comparison of the number of release sites estimated from paired recordings with those estimated from responses evoked by ventral root stimulation revealed that on average six motoneurons project onto every Renshaw cell. We conclude that: • In mature animals motoneuron inhibition is mainly glycinergic. • The Renshaw cell to motoneuron synapse has a high efficiency of transmission. • The degree of convergence of motoneurons to Renshaw cells is very high. The last two conclusions suggest that firing in motoneurons pools reliably induces firing in the population of connected Renshaw cells

Modelling self-sustained rhythmic activity in lamprey hemisegmental networks

Recent studies of the lamprey spinal cord have shown that hemisegmental preparations can display rhythmic activity in response to a constant input drive. This activity is believed to be generated by a network of recurrently connected excitatory interneurons. A recent study found and characterized self-sustaining rhythmic activity—locomotor bouts—after brief electrical stimulation of hemisegmental preparations. The mechanisms behind the bouts are still unclear. We have developed a computational model of the hemisegmental network. The model addresses the possible involvement of NMDA, AMPA, acetylcholine, and metabotropic glutamate receptors as well as axonal delays in locomotor bouts