Neuronal Generation of the Leech Swimming Movement

Stent, Gunther S.; Kristan, WB; Friesen, W. Otto; Ort, CA; Poon, M; Calabrese, RL

doi:10.1126/science.663615

Cited by 188 publications

(88 citation statements)

References 30 publications

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“…These segmental oscillators are interconnected in a chain through the nerve cord, with intersegmental projections spanning about six segments. These complex interneuron circuits, comprising local, non-spike-mediated synaptic interactions and intersegmental, spike-mediated connections, form the CPG for leech swimming (19)(20)(21)(22).…”

Section: Resultsmentioning

confidence: 99%

“…We use the simple three-neuron model because the details within each segment are not important for intersegmental phase coordination as long as the intrasegmental phases are captured correctly (23), and model complexity can then be significantly reduced. Dynamics for neurons and their synaptic interactions were modeled by a threshold function, time lag, and communication delay using experimentally derived input-output membrane potential data (21,(24)(25)(26). Topological structures in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Biological clockwork underlying adaptive rhythmic movements

Iwasaki

Friesen

2014

Proc. Natl. Acad. Sci. U.S.A.

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Owing to the complexity of neuronal circuits, precise mathematical descriptions of brain functions remain an elusive ambition. A more modest focus of many neuroscientists, central pattern generators, are more tractable neuronal circuits specialized to generate rhythmic movements, including locomotion. The relative simplicity and welldefined motor functions of these circuits provide an opportunity for uncovering fundamental principles of neuronal information processing. Here we present the culmination of mathematical analysis that captures the adaptive behaviors emerging from interactions between a central pattern generator, the body, and the physical environment during locomotion. The biologically realistic model describes the undulatory motions of swimming leeches with quantitative accuracy and, without further parameter tuning, predicts the sweeping changes in oscillation patterns of leeches undulating in air or swimming in high-viscosity fluid. The study demonstrates that central pattern generators are capable of adapting oscillations to the environment through sensory feedback, but without guidance from the brain.A long-term ambition in neuroscience is to generate a detailed, complete model of the human brain (1). Still ambitious, and certainly more realistic, is the aim to model components of vertebrate nervous systems. Most advanced in this arena are models based on the circuits underlying motor functions, such as rhythmic body movements during locomotion. These movements are generated by spinal neural oscillator circuits called central pattern generators (CPGs) (2, 3). The enormous number of neurons in the vertebrate central nervous system currently prevents analysis at the level of defined circuits between individual neurons. However, the simpler, accessible CPGs underlying locomotion in the invertebrates provide dynamically rich platforms amenable to detailed analysis that can lead to deep understanding of how neuronal circuits generate extremely robust and adaptive oscillatory behaviors. The leech CPG for undulatory swimming provides such a platform. The isolated nerve cord, with most (4, 5), a few (6, 7), or even a single segmental ganglion (8, 9), displays "fictive swimming," where the rhythmic motor pattern closely resembles that recorded in intact animals. Moreover, the leech continues to swim without the brain (10, 11), with the nerve cord severed in midbody (5), or with the body cut in half (7).Our study addresses the following question: How does the leech swimming system achieve its astonishing robustness and adaptability? A detailed explanation of the mechanisms underlying such complex phenomena requires mathematical modeling and analysis because a unidirectional sequence of cause-andeffect relationships alone cannot explain dynamical properties arising from multiple feedback loops. An obstacle in exploring the emergence of the functional properties from highly interconnected neuronal circuits through model-based analysis is the lack of biological realism (1). We, therefore, have focused on the...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Biological clockwork underlying adaptive rhythmic movements

Iwasaki

Friesen

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Because the role of sensory inputs in rhythmic behavior has often been assessed based on surgical operations to remove sensory inputs, it raises such concerns about whether all sensory inputs are blocked or whether motor outputs remain intact after surgical operation (1), which might be the reason why different laboratories achieved different results with the same protocols (24)(25)(26)(27). It is also difficult to study animal behavior following the surgical operation.…”

Section: Neuron Function Is Required For the Formation Of Rhythmicmentioning

confidence: 99%

Peripheral multidendritic sensory neurons are necessary for rhythmic locomotion behavior in Drosophila larvae

Song

Onishi

Jan

2007

Proc. Natl. Acad. Sci. U.S.A.

167

178

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From breathing to walking, rhythmic movements encompass physiological processes important across the entire animal kingdom. It is thought by many that the generation of rhythmic behavior is operated by a central pattern generator (CPG) and does not require peripheral sensory input. Sensory feedback is, however, required to modify or coordinate the motor activity in response to the circumstances of actual movement. In contrast to this notion, we report here that sensory input is necessary for the generation of Drosophila larval locomotion, a form of rhythmic behavior. Blockage of all peripheral sensory inputs resulted in cessation of larval crawling. By conditionally silencing various subsets of larval peripheral sensory neurons, we identified the multiple dendritic (MD) neurons as the neurons essential for the generation of rhythmic peristaltic locomotion. By recording the locomotive motor activities, we further demonstrate that removal of MD neuron input disrupted rhythmic motor firing pattern in a way that prolonged the stereotyped segmental motor firing duration and prevented the propagation of posterior to anterior segmental motor firing. These findings reveal that MD sensory neuron input is a necessary component in the neural circuitry that generates larval locomotion.rhythmic behavior ͉ sensory feedback ͉ locomotion generation ͉ motor pattern ͉ central pattern generator R hythmic behaviors comprise a cyclic, repetitive set of movements, such as locomotion, respiration, and mastication (1, 2). The prevailing model for the neural basis underlying rhythmic behavior is that all rhythmic movements are generated by specialized circuits within the CNS called central pattern generators (CPGs), which can operate without sensory inputs (3-5). Nevertheless, a functional motor program also requires sensory inputs reporting peripheral feedback due to the actual movements to produce the correct behavior (6, 7). This model draws support from reports of sensory feedback affecting the timing and magnitude of motor activity generated by CPGs and from studies based on surgical removal of afferent input (1, 4, 6, 7). Whereas there are electrophysiological demonstrations of the influence of sensory feedback on the output of CPGs, how interactions between sensory neurons in the peripheral and neurons in the CNS contribute to rhythmic behavior in an intact organism is not known. It is therefore important to ask whether sensory inputs are essential for rhythmic behavior and how sensory inputs contribute to rhythmic behavior.Drosophila is ideal for investigations of neural circuits underlying rhythmic behavior due to its amenability to genetic manipulation. Larval crawling, used for travel across various types of terrain, is accomplished by repeated peristaltic wave-like strides (8) and involves molecules mediating neuronal signaling (9-12). Whereas one study suggests that embryonic assembly of CPG for larval locomotion does not require sensory inputs, the same study reports that interference with the sensory function during embry...

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“…Inhibitory synaptic connections have been found to play an essential role in the generation of the rhythmic motor patterns in the leech (Stent et al, 1978(Stent et al, , 1979. GABA, whose inhibitory synaptic action has been documented in other invertebrates, notably in another annelid, the earthworm and in crustaceans (Otsuka, 1976), is a likely candidate for the neurotransmitter at some of these synapses.…”

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confidence: 99%

“…Both cells 1 and 2 innervate the L motor neuron, which provides excitatory synaptic input to both dorsal and ventral longitudinal muscles Stuart, 1970). The inhibitors and excitors of the longitudinal muscles can be unambiguously identified in Hirudo medicinalis, according to the position of their cell bodies in the segmental ganglion, their synaptic connections, the amplitude and shape of the action potentials recorded in their cell bodies, and the pattern of the axonal projections in identified peripheral nerves (Granzow et al, 1985;Ort et al, 1974;Poon, 1976;Stent et al, 1978;Stuart, 1970).…”

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confidence: 99%

Evidence for GABA as a neurotransmitter in the leech

Cline¹

1986

J. Neurosci.

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In the leech, Hirudo medicinalis, the inhibitory motor neurons to the longitudinal muscles in the body wall, cells 1 and 2, are linked via central inhibitory synapses to the excitatory motor neurons innervating the same muscles. Examination of these synapses showed that the inhibitors are GABAergic according to several electrophysiological and pharmacological criteria. Presynaptic release of neurotransmitter during passage of depolarizing current into the inhibitors, as well as direct application of GABA to the excitor cell bodies, hyperpolarizes the postsynaptic excitor. Moreover, both synaptic and extrasynaptic GABA receptors of the excitors are specifically blocked by the GABA antagonist bicuculline methiodide. The inhibitors, dissected from the ganglion and grown in culture, synthesize GABA when exposed to the GABA precursor glutamate, whereas the excitors do not synthesize detectable levels of GABA under these same conditions. The innervation and neurotransmitter sensitivity of the longitudinal muscles in the body wall of the glossiphoniid leeches Haementeria ghilianii and H. oficinalis were examined in order to determine if the inhibitory neurotransmitter at the neuromuscular junction is GABA. Individual muscle fibers are innervated by both inhibitory and excitatory motor neurons in a manner such that the inhibitory and excitatory nerve terminals and neurotransmitter receptors are spatially and electrically separate. Intracellular recordings taken from the muscle fibers reveal a resting potential of about -70 mV. The amplitude of the spontaneous inhibitory junctional potentials (IJPs) falls to zero at a polarization of about -65 mV and reverses in sign at the normal resting potential. Application of GABA to inhibitory junctional sites results in an increased conductance of the muscle fiber membrane and a polarization with a reversal potential of about -65 mV. Bicuculline methiodide blocks reversibly the GABA response and all spontaneous IJPs, without blocking the spontaneous excitatory junctional potentials (EJPs) recorded from the excitatory junctional sites.

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Neuronal Generation of the Leech Swimming Movement

Cited by 188 publications

References 30 publications

Biological clockwork underlying adaptive rhythmic movements

Biological clockwork underlying adaptive rhythmic movements

Peripheral multidendritic sensory neurons are necessary for rhythmic locomotion behavior in Drosophila larvae

Evidence for GABA as a neurotransmitter in the leech

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