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

Neural circuits controlling behavior and autonomic functions in medicinal leeches

In the study of the neural circuits underlying behavior and autonomic functions, the stereotyped and accessible nervous system of medicinal leeches, Hirudo sp., has been particularly informative. These leeches express well-defined behaviors and autonomic movements which are amenable to investigation at the circuit and neuronal levels. In this review, we discuss some of the best understood of these movements and the circuits which underlie them, focusing on swimming, crawling and heartbeat. We also discuss the rudiments of decision-making: the selection between generally mutually exclusive behaviors at the neuronal level

A kinematic and computational study of leech crawling: Support for a CPG based on travelling waves of excitation.

Many well characterized central pattern generators (CPGs) underlie behaviors (e.g., swimming, flight, heartbeat) that require regular rhythmicity and strict phase relationships. Here, we examine the organization of a CPG for leech crawling, a behavior whose success depends more on its flexibility than on its precise coordination. We examined the organization of this CPG by first characterizing the kinematics of crawling steps in normal and surgically manipulated animals, then by exploring its features in a simple neuronal model. The behavioral observations revealed the following. (1) Intersegmental coordination varied considerably with step duration, whereas the rates of elongation and contraction within individual segments were relatively constant. (2) Steps were generated in the absence of both head and tail brains, implying that midbody ganglia contain a CPG for step production. (3) Removal of sensory feedback did not affect step coordination or timing. (4) Imposed stretch greatly lengthened transitions between elongation and contraction, indicating that sensory pathways feed back onto the CPG. A simple model reproduced essential features of the observed kinematics. This model consisted of an oscillator that initiates propagating segmental waves of activity in excitatory neuronal chains, along with a parallel descending projection; together, these pathways could produce the observed intersegmental lags, coordination between phases, and step duration. We suggest that the proposed model is well suited to be modified on a step-by-step basis and that crawling may differ substantially from other described CPGs, such as that for swimming in segmented animals, where individual segments produce oscillations that are strongly phase-locked to one another

Identification and Characterization of electrical patterns underlying stereotyped behaviours in the semi-intact leech

Neuroscience aims at understanding the mechanisms underlying perception, learning, memory, consciousness and acts. The present Ph.D. thesis aims to elucidate some principles controlling actions, which in a more scientific and technical language is referred to as motor control. This concept has been studied in a variety of preparations in vertebrate and invertebrate species. In this PhD thesis, the leech has been the subject of choice, because it is a well known preparation, highly suitable for relating functional and behavioural properties to the underlying neuronal networks. The semi-intact leech preparation (Kristan et al., 1974) has been the main methodological strategy performed in the experiments. Its importance lies in the fact that it gives the possibility to access the information from the leech\u2019s central nervous system (CNS) and compare simultaneously some stereotyped behaviours. Thus, entering in this work it is necessary to make a brief summary of the steps followed before arriving to the conclusions written ahead. The main objective followed in this work has been the analysis, identification and characterization of electrical patterns underlying different behaviours in Hirudo medicinalis. This main objective has been reached focusing the project on three particular objectives, which have been pursued during the author\u2019s Philosophical Doctorate course

Control strategies of 3-cell Central Pattern Generator via global stimuli

The study of the synchronization patterns of small neuron networks that control several biological processes has become an interesting growing discipline. Some of these synchronization patterns of individual neurons are related to some undesirable neurological diseases, and they are believed to play a crucial role in the emergence of pathological rhythmic brain activity in different diseases, like Parkinson''s disease. We show how, with a suitable combination of short and weak global inhibitory and excitatory stimuli over the whole network, we can switch between different stable bursting patterns in small neuron networks (in our case a 3-neuron network). We develop a systematic study showing and explaining the effects of applying the pulses at different moments. Moreover, we compare the technique on a completely symmetric network and on a slightly perturbed one (a much more realistic situation). The present approach of using global stimuli may allow to avoid undesirable synchronization patterns with nonaggressive stimuli

Mechanisms of the Coregulation of Multiple Ionic Currents for the Control of Neuronal Activity

An open question in contemporary neuroscience is how neuromodulators coregulate multiple conductances to maintain functional neuronal activity. Neuromodulators enact changes to properties of biophysical characteristics, such as the maximal conductance or voltage of half-activation of an ionic current, which determine the type and properties of neuronal activity. We apply dynamical systems theory to study the changes to neuronal activity that arise from neuromodulation. Neuromulators can act on multiple targets within a cell. The coregulation of mulitple ionic currents extends the scope of dynamic control on neuronal activity. Different aspects of neuronal activity can be independently controlled by different currents. The coregulation of multiple ionic currents provides precise control over the temporal characteristics of neuronal activity. Compensatory changes in multiple ionic currents could be used to avoid dangerous dynamics or maintain some aspect of neuronal activity. The coregulation of multiple ionic currents can be used as bifurcation control to ensure robust dynamics or expand the range of coexisting regimes. Multiple ionic currents could be involved in increasing the range of dynamic control over neuronal activity. The coregulation of multiple ionic currents in neuromodulation expands the range over which biophysical parameters support functional activity

A Hormone-Activated Central Pattern Generator for Courtship

Background: Medicinal leeches (Hirudo spp.) are simultaneous hermaphrodites. Mating occurs after a stereotyped twisting and oral exploration that result in the alignment of the male and/or female gonopores of one leech with the complementary gonopores of a partner. The neural basis of this behavior is presently unknown and currently impossible to study directly because electrophysiological recording techniques disrupt the behavior. Results: Here we report that (Arg^8)-conopressin G and two other members of the oxytocin/vasopressin family of peptide hormones induce in Hirudo verbana a sequence of behaviors that closely mimic elements of spontaneous reproductive behavior. Through a series of progressively more reduced preparations, we show that one of these behaviors, a stereotyped twisting that is instrumental in aligning gonopores in preparation for copulation, is the product of a central pattern generator that consists of oscillators in ganglia M5 and M6 (the ganglia in the reproductive segments of the leech), and also in ganglion M4, which was not previously known to play a role in reproductive behavior. We find that the behavior is periodic, with a remarkably long cycle period of around five minutes, placing it among the slowest behavioral rhythms (other than diurnal and annual rhythms) yet described. Conclusion: These results establish the leech as a new model system for studying aspects of the neuronal basis of reproductive behavior. Highlights: Oxytocin/vasopressin homologs induce precopulatory movements in a leech. These movements are generated by a central pattern generator. Segmental ganglia M4, M5, and M6 can each generate fictive behavior in isolatio

Imaging fictive locomotor patterns in larval Drosophila.

We have established a preparation in larval Drosophila to monitor fictive locomotion simultaneously across abdominal and thoracic segments of the isolated CNS with genetically encoded Ca(2+) indicators. The Ca(2+) signals closely followed spiking activity measured electrophysiologically in nerve roots. Three motor patterns are analyzed. Two comprise waves of Ca(2+) signals that progress along the longitudinal body axis in a posterior-to-anterior or anterior-to-posterior direction. These waves had statistically indistinguishable intersegmental phase delays compared with segmental contractions during forward and backward crawling behavior, despite being ∼10 times slower. During these waves, motor neurons of the dorsal longitudinal and transverse muscles were active in the same order as the muscle groups are recruited during crawling behavior. A third fictive motor pattern exhibits a left-right asymmetry across segments and bears similarities with turning behavior in intact larvae, occurring equally frequently and involving asymmetry in the same segments. Ablation of the segments in which forward and backward waves of Ca(2+) signals were normally initiated did not eliminate production of Ca(2+) waves. When the brain and subesophageal ganglion (SOG) were removed, the remaining ganglia retained the ability to produce both forward and backward waves of motor activity, although the speed and frequency of waves changed. Bilateral asymmetry of activity was reduced when the brain was removed and abolished when the SOG was removed. This work paves the way to studying the neural and genetic underpinnings of segmentally coordinated motor pattern generation in Drosophila with imaging techniques.S.R.P. was supported by a Newton International Fellowship (Royal Society) and a Junior Fellowship (Janelia Research Campus, Howard Hughes Medical Institute). T.G.B. was supported by a Medical Research Council (UK) PhD grant. J.B. was supported by a Henry Dale Fellowship (Royal Society and Wellcome Trust). M.B. was supported by the Isaac Newton Trust.This is the final version of the article. It first appeared from the American Physiological Society via http://dx.doi.org/10.1152/jn.00731.201

From neuronal networks to behavior: dynamics of spontaneous activity and onset of movement in the leech

Animal behavior was once seen as a chain of reactions to stimuli from the environment. From chemotaxis in bacteria to mammals withdrawing from painful stimuli, most of the actions taken by animals are clearly driven by external inputs. Reflexes were among the first phenomena to be studied to have an insight on the dynamics of the nervous system. Later, a step forward was the discovery of central pattern generators: once a behavior is started by a stimulus, some neuronal networks are able to maintain it without further inputs from the environment. The nervous system of all animals, however, is so complex that is displaying a rich dynamics even in the absence of external inputs or, in a more realistic situation, when no single input is able to drive a clear-cut reaction. In the same way, at the motor output level, animals keep moving in the absence of evident stimuli. These spontaneous behaviors are still far from being understood. Difficult problems are often easier to solve in simple systems. The leech has a relatively simple nervous system, composed of ~103 neurons disposed in a regular structure, but at the same time displays a variety of different behaviors. It seems then a good preparation to approach the spontaneous dynamics problem. The aim of my PhD research is to describe the spontaneous behavior of the leech and the spontaneous activity of its nervous system. A first, necessary step for this study was to develop a method of automatic classification and analysis of the leech movements. Thanks to this method we described accurately the properties of the different behaviors: we focused particularly on the largely unknown irregular exploratory behavior, which is found to display a broad range of oscillation frequencies and displacement speeds, but with some recurrent movement patterns. Finding the complete list of the leech spontaneous behaviors, and the probability of the transitions between them, it was possible to demonstrate that decision making in the leech is a Markovian process. The spontaneous activity in the isolated leech ganglion was found to be characterized by long-term correlations and a large variability in bursts size and duration. The same dynamics was observed in dissociated culture of rat hippocampal neurons, despite the difference in the structure between the two networks. We studied the effects of pharmacological modulations of inhibitory and excitatory processes on the spontaneous activity, and the role of single identified motor neurons in spontaneous bursts. Finally we proposed a simple statistical model accounting for experimental results. We studied then the spontaneous activity of the leech ganglion when it was connected to the other ganglia and in the semi-intact moving animal. Inputs received from the head and tail brain caused a drastic change in the activity of the ganglion, increasing synchronization among neurons and leading to a regime dominated by very large bursts. By recording at the same the movements of the leech and its nervous activity it was possible to have a better understanding of the relationship between the motor neuron bursts and the onset of movements