Ритмдік кіріспесіз жұмыс істейтін нейрондық тізбектер

Biological neural circuit that produces rhythmic outputs in the absence of rhythmic input

Central pattern generators (CPGs) are self organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly coupled patterns of neural activity that drive rhythmic and stereotyped motor behaviors like walking, swimming, breathing, or chewing. The ability to function without input from higher brain areas still requires modulatory inputs, and their outputs are not fixed. Flexibility in response to sensory input is a fundamental quality of CPG driven behavior.

[[File:Intrinsic properties of CPG neurons. svg|thumb|440x440px|Intrinsic properties of CPG neurons. Adapted from Marder and Bucher (2001). Some neurons fire bursts of action potentials, either endogenously or in the presence of neuromodulatory substances. Other neurons are bistable and generate plateau potentials that can be triggered by a depolarizing current pulse, and terminated by a hyperpolarizing current pulse. Many CPG neurons fire after being released from inhibition (postinhibitory rebound). Another common feature of CPG neurons is a decrease in the frequency of firing during a constant depolarization (spike frequency adaptation).

A three phase model is the classical view of the respiratory CPG. The phases of the respiratory CPG are characterized by the rhythmic activity of: (1) the phrenic nerve during inspiration; (2) recurrent laryngeal nerve branches that innervate the thyroarytenoid muscle during the last stage of expiration; (3) the internal intercostal nerve branches that innervate the triangularis sterni muscle during the second stage of expiration. The rhythmicity of these nerves is classically viewed as originating from a single rhythm generator. In this model, phasing is produced by reciprocal synaptic inhibition between groups of sequentially active interneurons. Nevertheless, an alternative model has been proposed reinforced by certain experimental data. According to this model, respiratory rhythm is generated by two coupled anatomically distinct rhythm generators, one in the pre Boetzinger complex and the other in the retrotrapezoid nucleus / parafacial respiratory group. Further survey provided evidence to the hypothesis that one of the networks is responsible for inspiration rhythm and the other for expiration rhythm. Therefore, inspiration and expiration are distinct functions and one does not induce the other, as is the common belief, but one of two dominates the behavior by generating a faster rhythm.

Swallowing involves the coordinated contraction of more than 25 pairs of muscles in the oropharynx, larynx and esophagus, which are active during an oropharyngeal phase, followed by the primary esophageal peristalsis. Swallowing depends on a deglutition centre, a CPG located in the medulla oblongata, which involves several brain stem motor nuclei and two main groups of interneurons: a dorsal swallowing group (DSG) in the nucleus tractus solitarii and a ventral swallowing group (VSG) located in the ventrolateral medulla above the nucleus ambiguus. Neurons in the DSG are responsible for the generation of the swallowing pattern, while those in the VSG distribute the commands to the various motoneuronal pools. As in other CPGs, the functioning of the central network can be modulated by peripheral and central inputs, so that the swallowing pattern is adapted to the size of the bolus. Within this network, central inhibitory connections play a major role, producing a rostrocaudal inhibition that parallels the rostrocaudal anatomy of the swallowing tract. Thus, when the neurons controlling the proximal parts of the tract are active, those that command more distal parts are inhibited. Apart from the type of connection between the neurons, intrinsic properties of the neurons, especially those of NTS neurons, probably also contribute to the shaping and timing of the swallowing pattern. The swallowing CPG is a flexible CPG. This means that at least some of the swallowing neurons may be multifunctional neurons and belong to pools of neurons that are common to several CPGs. One such CPG is the respiratory one, which has been observed interacting with the swallowing CPG.

Central pattern generators can also play a role in rhythm generation for other functions in vertebrates. For example, the rat vibrissa system uses an unconventional CPG for whisking movements. "Like other CPGs, the whisking generator can operate without cortical input or sensory feedback. However, unlike other CPGs, vibrissa motoneurons actively participate in rhythmogenesis by converting tonic serotonergic inputs into the patterned motor output responsible for movement of the vibrissae." Breathing is another non locomotive function of central pattern generators. For example, larval amphibians accomplish gas exchange largely through rhythmic ventilation of the gills. A study showed that lung ventilation in the tadpole brainstem may be driven by a pacemaker like mechanism, whereas the respiratory CPG adapts in the adult bullfrog as it matures. Thus, CPGs hold a broad range of functions in the vertebrate animal and are widely adaptable and variable with age, environment and behavior.

Rhythmicity in CPGs can also result from time dependent cellular properties such as adaptation, delayed excitation, and post inhibitory rebound (PIR). PIR is an intrinsic property that elicits rhythmic electrical activity by depolarizing the membrane once hyperpolarizing stimulus is gone. It can be produced by several mechanisms including hyperpolarization activated cation current (Ih), low voltage activated calcium current, or deinactivation of depolarization activated inward currents. Once inhibition has ceased, this period of PIR can be explained as the time with increased neuronal excitability. It is the property of many CNS neurons that sometimes results in action potential "bursts" following immediately after inhibitory synaptic input. "Because of this, it has been suggested that PIR may contribute to the maintenance of oscillatory activity in neural networks that are characterized by mutual inhibitory connections, like those involved in locomotor behaviors. In addition, PIR is often included as an element in computational models of neural networks that involve mutual inhibition". For example, the "PIR in crayfish stretch receptor neurons is caused by recovery from adaptation during the course of inhibitory hyperpolarization. One feature of that system is that PIR only occurs if the hyperpolarization is imposed on a background of excitation, caused in this case by stretch. They also found that PIR can be elicited in the stretch receptor by hyperpolarizing current pulses. This was an important finding because it showed that PIR is an intrinsic property of the postsynaptic neuron, related to the membrane potential change associated with inhibition but independent of transmitter receptors or presynaptic properties. The latter conclusion has stood the test of time, marking PIR as a robust property of CNS neurons in a wide variety of contexts." This cellular property can most easily be seen in the Lamprey neural circuit. The swimming movement is produced by alternating neural activity between the left and right side of the body, causing it to bend back and forth while creating oscillating movements. While the Lamprey is bent to the left, there is reciprocal inhibition on the right side causing it to relax due to hyperpolarization. Immediately after this hyperopolarizing stimulus, the interneurons use post inhibitory rebound to initiate activity in the right side. Depolarization of the membrane causes it to contract while reciprocal inhibition is now applied to the left side.

CPGs play a similarly critical role in coordinating behaviors in invertebrates, and studying invertebrate CPGs with fewer numbers of neurons has helped establish general principles of CPGs and their organization in the nervous system. One model circuit for studying CPGs is the stomatogastric ganglion in crabs and lobsters, a ~30 neuron circuit containing two CPGs that generate rhythmic motor output for chewing and digesting food. Continued research into how CPGs control these behaviors has revealed a nested CPG architecture to control rhythmic behaviors across various timescales. Other examples of CPGs in invertebrate animals include a CPG modulating reflexive withdrawal, escape swimming and crawling in the mollusc Tritonia, and to control the heartbeat of leeches. Central pattern generators play a broad role in all animals and show amazing variability and adaptability in almost all cases.

One theory that reconciles the role of sensory feedback during rhythmic locomotion is to redefine CPGs as "state estimators" as opposed to rhythm generators. Through this perspective, CPGs are an intrinsic spinal processor that corrects imperfect sensory feedback and adapts central input to this optimized peripheral input. Models using this framework are able to accomplish rhythmic behavior as well as fictive locomotion without incorporating independent rhythm generators.