Role of Opioid Peptides in Behavior of Invertebrates

Opioid peptides have been revealed in representatives of practically all large taxonomic groups of invertebrates, and the opiate receptors are found even in unicellulars. The opioid system seems to belong to the evolutionary ancient signal systems. The comparative data indicate that the most conservative and ancient function of opioids is control of the adequate level of protective reactions. In the infusorian Stentor the opiate ligands suppress a contractile response to mechanical stimulation, i.e., the protective behavior. In all studies multicellular invertebrates, agonists also suppress protective behavior, whereas antagonists produce opposite effects. This initially signal meaning of opioids might have become a basis for divergent development of their functions in evolution. Already in higher invertebrates, molluscs and arthropods, many functions of opioids, for example, stress-induced analgesia, regulation of feeding and mating behavior, of social aggression, are similar to those in vertebrates. It is suggested that the main events in formation of functions of the endogenous opioid system have occurred in the lower invertebrates that have remained so far the least studied.     

Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements

The sequential stepping of left and right limbs is a fundamental motor behavior that underlies walking movements. This relatively simple locomotor behavior is generated by the rhythmic activity of motor neurons under the control of spinal neural networks known as central pattern generators (CPGs) that comprise multiple interneuron cell types. Little, however, is known about the identity and contribution of defined interneuronal populations to mammalian locomotor behaviors. We show a discrete subset of commissural spinal interneurons, whose fate is controlled by the activity of the homeobox gene Dbx1, has a critical role in controlling the left-right alternation of motor neurons innervating hindlimb muscles. Dbx1 mutant mice lacking these ventral interneurons exhibit an increased incidence of cobursting between left and right flexor/extensor motor neurons during drug-induced locomotion. Together, these findings identify Dbx1-dependent interneurons as key components of the spinal locomotor circuits that control stepping movements in mammals.     

Motor activity of infusoria: fundamental and applied aspects

The article considers morpho-functional organization of the cilia, locomotor organelle of the infusoria, and demonstrates the complicity of locomotor behavior of these protista. The problem of control of locomotion of infusoria is whole organism in discussed; and conclusion is drawn that system of control of movements could be multilevel and include receptor, afferent, central, efferent and effector units. In this context the macronucleus, could act as a central integrator and coordinator of the locomotor behavior being closely connected with periphery by dynamic elements of cytoskeleton. The eradication of infusoria parasitizing in humans and animals by interrupting of locomotion of the protista is also discussed.     

Roles of the Caudate Nuclei, Cerebellum, and Caudato-Cerebellar Interconnections in the Control and Coordination of Ballistic Food-Procuring Movements

We studied the roles of the cerebellum and caudate nuclei in the programming and control of ballistic movements. An experimental model of operant food-procuring movements of the rats was used; the activity of single neurons of the above structures was recorded in the course of these motor performances. To evaluate the impact of the cerebellar–caudate interaction on the process of control of the ballistic (centrally programmed) components of food-procuring motor performance, we also recorded modifications of the neuronal activity in one of the above-mentioned structures induced by electrical extrastimulation of another structure in the course of realization of the above components. It is demonstrated that the cerebellum and, in particular, its dentate nuclei are involved in the programming of ballistic food-procuring movements. Neurons of the caudate nuclei play a significant role in the immediate preparation for and subsequent current control of stereotyped ballistic movements. The high plastic properties of the cerebellar neurons manifested in the process of control of ballistic food-procuring movements are proved.     

Automated Food-Procuring Movement-Related Neuronal Activity in the Basolateral Amygdala of the Rat

We studied the impulse activity of neurons of the basal and lateral amygdalar nuclei generated when experimental animals (rats) performed fast stereotyped food-procuring movements by the forelimb. Within the basolateral amygdala, there are neurons whose activity is related to different stages of getting off the food, and according to the characteristics of their spiking these neurons should be divided into a number of subpopulations. Activation forestalling the movement initiation by 0.5-1.0 sec was observed in most neurons of the basolateral amygdala; this is considered a manifestation of excitation related to a motivation component of the food-procuring behavior. Activation of amygdalar neurons following movement initiation can result from generation in this structure of additional excitation necessary for successful performance of a complete food-procuring motor cycle.     

Physiological and Neurochemical Aspects of Corticotropin-Releasing Factor Actions in the Brain: The Role of the Locus Coeruleus

Corticotropin-releasing factor (CRF) is both a major regulator of the hypothalamo-pituitary-adrenal (HPA) axis and the activity of the autonomic nervous system. Besides, it exerts numerous effects on other physiological functions such as appetite control, motor and cognitive behavior and immune function. The basis for these effects is constituted by its distribution in hypothalamic and extrahypothalamic brain areas, the latter being represented by limbic structures such as the central nucleus of the amygdala or by brain stem neurons such as the locus coeruleus (LC) or nucleus of the solitary tract (NTS). The effects of CRF are mediated through recently described CRF-receptor subtypes, whose molecular biology, biochemistry and pharmacological regulation are discussed in detail. In the second part of this review, we will focus on the physiology of CRF-systems in the brain, with a particular emphasis on cardiovascular regulation, respiration, appetite control and stress-related behavior. Finally, the role of the locus coeruleus in the control of CRF-mediated behavioral activities is discussed. The interaction of noradrenergic and CRF-neurons clearly implies that CRF appears to directly activate LC neurons in a stressful situation, thus ultimately coordinating the bodily response to a stressful stimulus.     

Role of central and peripheral mechanisms in control of excitability of segmental motor centers in insects

The role of central and peripheral mechanisms in control of excitability of segmental centers providing different motor acts in insects of phylogenic close orders, but differing by the level of activity of their locomotor systems has been studied in the locust Locusta migratoria and the cockroach Periplaneta americana. It was shown that the level of relative excitability of segmental centers in cockroaches seemed to be much determined by the peripheral mechanisms, but not by the central mechanisms as in locust. It is suggested that control of activity of segmental locomotor centers from the higher parts of CNS can be realized by different ways: predominantly via excitatory or inhibitory influences on activity id some particular locomotor systems depending on their role and significance in motor behavior of these animals.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 6, 2004, pp. 508–513.Original Russian Text Copyright © 2004 by Gorelkin, Severina.To the 100-Anniversary of A. K. VoskresenskayaThis revised version was published online in April 2005 with a corrected cover date.     

Regulatory calcium effect on adenylyl cyclase functional activity in the infusorian <Emphasis Type="Italic">Dileptis anser</Emphasis>

Earlier we have shown that some non-hormonal activators of adenylyl cyclase (AC) and hormones of higher vertebrate animals are able to affect functional activity of the AC system in the infusorian Dileptus anser. In the present work, sensitivity of this infusorian AC to Ca²⁺ was studied and it was found that calcium cations at concentrations of 0.5–10 μM stimulated significantly the enzyme activity in D. anser partially purified membranes. An increase of Ca²⁺ concentrations to 100 μM and higher led to the complete block of their stimulatory effect. In the EDTA-treated membranes the enzyme activity was reduced markedly, but it was restored significantly by addition of Ca²⁺. Calmodulin antagonists—chlorpromazine, W-7, and W-5—caused a dose-dependent decrease of the enzyme activity stimulated by 5 μM Ca²⁺ with IC₅₀ values of 35, 137, and 174 M, respectively. The AC-stimulating effects of biogenic amines (serotonin and octopamine) were completely retained in the presence of 2.5 and 100 μM Ca²⁺, whereas effects of peptide hormones (relaxine and EGF) were hardly changed in the presence of 2.5 μM calcium ions, but were markedly inhibited by 100 μM Ca²⁺. In the EDTA-treated membranes, the AC effects of biogenic amines were reduced, while the effects of peptide hormones were not revealed. On addition of Ca²⁺, the AC effects of biogenic amines were completely restored, whereas the effects of peptide hormones were not detected or restored to a non-significant degree. Calmodulin antagonists slightly affected the AC effects of peptide hormones at concentrations efficient in the case of vertebrate AC, but decreased them markedly at higher concentrations. The AC effects of biogenic amines were little sensitive even to high antagonist concentrations. The obtained data show that targets of action of peptide hormones in the infusorian D. anser cell culture are the AC forms whose activity depends on calcium cations and possibly is regulated by Ca²⁺/calmodulin, whereas targets of action of biogenic amines are calcium-independent enzyme forms.     

Neural Coding of Finger and Wrist Movements

Previous work (Schieber and Hibbard, 1993) has shown that single motor cortical neurons do not discharge specifically for a particular flexion-extension finger movement but instead are active with movements of different fingers. In addition, neuronal populations active with movements of different fingers overlap extensively in their spatial locations in the motor cortex. These data suggested that control of any finger movement utilizes a distributed population of neurons. In this study we applied the neuronal population vector analysis (Georgopoulos et al., 1983) to these same data to determine (1) whether single cells are tuned in an abstract, three-dimensional (3D) instructed finger and wrist movement space with hand-like geometry and (2) whether the neuronal population encodes specific finger movements. We found that the activity of 132/176 (75%) motor cortical neurons related to finger movements was indeed tuned in this space. Moreover, the population vector computed in this space predicted well the instructed finger movement. Thus, although single neurons may be related to several disparate finger movements, and neurons related to different finger movements are intermingled throughout the hand area of the motor cortex, the neuronal population activity does specify particular finger movements.     

Novel peripheral motor neurons in the posterior tentacles of the snail responsible for local tentacle movements

Three flexor muscles of the posterior tentacles of the snail Helix pomatia have recently been described. Here, we identify their local motor neurons by following the retrograde transport of neurobiotin injected into these muscles. The mostly unipolar motor neurons (15–35 µm) are confined to the tentacle digits and send motor axons to the M2 and M3 muscles. Electron microscopy revealed small dark neurons (5–7 µm diameter) and light neurons with 12–18 (T1 type) and 18–30 µm diameters (T2 type) in the digits. The diameters of the neurobiotin-labeled neurons corresponded to the T1 type light neurons. The neuronal processes of T1 type motor neurons arborize extensively in the neuropil area of the digits and receive synaptic inputs from local neuronal elements involved in peripheral olfactory information processing. These findings support the existence of a peripheral stimulus–response pathway, consisting of olfactory stimulus—local motor neuron—motor response components, to generate local lateral movements of the tentacle tip (“quiver”). In addition, physiological results showed that each flexor muscle receives distinct central motor commands via different peritentacular nerves and common central motor commands via tentacle digits, respectively. The distal axonal segments of the common pathway can receive inputs from local interneurons in the digits modulating the motor axon activity peripherally without soma excitation. These elements constitute a local microcircuit consisting of olfactory stimulus—distal segments of central motor axons—motor response components, to induce patterned contraction movements of the tentacle. The two local microcircuits described above provide a comprehensive neuroanatomical basis of tentacle movements without the involvement of the CNS.     

Blockage of vibrissae afferents: I. Motor effects

In the past, it has been proposed that the rat vibrissae play an important role in other hand, postural abnormalities, muscle tone decreases and hypomotility after sensory organ destructions were proposed as evidence supporting the "level setting" or "tonic" hypothesis. This hypothesis postulates that afferent activity, besides its well know transductive functions, sets the excitability state of the central nervous system. We thought the vibrissal system to be a good model to dissect these two postulated roles because vibrissae trimming would annul the transductive function without affecting the integrity of nerve activity. Thus we compare the effects of trimming the whiskers with blocking the vibrissal afferent nerves on two types of motor behavior: activity in an open field and walking over a rope connecting two elevated platforms. We found that only vibrissal afferent blockage (both nerve section and local anaesthesia) produced severe failures in the motor performances studied. These effects could not be fully explained by the abolition of the vibrissae as a sensory modality because cutting the whiskers did not significantly affect the motor performance. These data are discussed in reference to a tonic or general excitatory function of sensory inputs upon the central nervous system.     

Invited review: Neural network plasticity in respiratory control.

Respiratory network plasticity is a modification in respiratory control that persists longer than the stimuli that evoke it or that changes the behavior produced by the network. Different durations and patterns of hypoxia can induce different types of respiratory memories. Lateral pontine neurons are required for decreases in respiratory frequency that follow brief hypoxia. Changes in synchrony and firing rates of ventrolateral and midline medullary neurons may contribute to the long-term facilitation of breathing after brief intermittent hypoxia. Long-term changes in central respiratory motor control may occur after spinal cord injury, and the brain stem network implicated in the production of the respiratory rhythm could be reconfigured to produce the cough motor pattern. Preliminary analysis suggests that elements of brain stem respiratory neural networks respond differently to hypoxia and hypercapnia and interact with areas involved in cardiovascular control. Plasticity or alterations in these networks may contribute to the chronic upregulation of sympathetic nerve activity and hypertension in sleep apnea syndrome and may also be involved in sudden infant death syndrome.     

Role of local nonspiking interneurons in the generation of rhythmic motor activity in the stick insect

Local nonspiking interneurons in the thoracic ganglia of insects are important premotor elements in posture control and locomotion. It was investigated whether these interneurons are involved in the central neuronal circuits generating the oscillatory motor output of the leg muscle system during rhythmic motor activity. Intracellular recordings from premotor nonspiking interneurons were made in the isolated and completely deafferented mesothoracic ganglion of the stick insect in preparations exhibiting rhythmic motor activity induced by the muscarinic agonist pilocarpine. All interneurons investigated provided synaptic drive to one or more motoneuron pools supplying the three proximal leg joints, that is, the thoraco-coxal joint, the coxa-trochanteral joint and the femur-tibia joint. During rhythmicity in 83% (n=67) of the recorded interneurons, three different kinds of synaptic oscillations in membrane potential were observed: (1) Oscillations were closely correlated with the activity of motoneuron pools affected; (2) membrane potential oscillations reflected only certain aspects of motoneuronal rhythmicity; and (3) membrane potential oscillations were correlated mainly with the occurrence of spontaneous recurrent patterns (SRP) of activity in the motoneuron pools. In individual interneurons membrane potential oscillations were associated with phase-dependent changes in the neuron's membrane conductance. Artificial changes in the interneurons' membrane potential strongly influenced motor activity. Injecting current pulses into individual interneurons caused a reset of rhythmicity in motoneurons. Furthermore, current injection into interneurons influenced shape and probability of occurrence for SRPs. Among others, identified nonspiking interneurons that are involved in posture control of leg joints were found to exhibit the above properties. From these results, the following conclusions on the role of nonspiking interneurons in the generation of rhythmic motor activity, and thus potentially also during locomotion, emerge: (1) During rhythmic motor activity most nonspiking interneurons receive strong synaptic drive from central rhythm-generating networks; and (2) individual nonspiking interneurons some of which underlie sensory-motor pathways in posture control, are elements of central neuronal networks that generate alternating activity in antagonistic leg motoneuron pools. © 1995 John Wiley & Sons, Inc.     

The endogenous opioid system in neurological disorders of the basal ganglia

The endogenous opioid peptides have for some time been implicated in the regulation of motor behavior in animals. Recently, however, there is increased evidence to suggest a role for these peptides in the control of human motor functions as well as in the pathophysiology of abnormal movement disorders. Degeneration of opioid peptide-containing neurons in the basal ganglia has been demonstrated in Parkinson's disease and Huntington's chorea, but the clinical significance of these findings is largely unknown. On the other hand, there is evidence that excessive opioid activity may be important in the pathophysiology of some movement disorders such as tardive dyskinesia, progressive supra-nuclear palsy, and a subgroup of Tourette's patients. These findings indicate that diseases of the basal ganglia are possibly associated with alterations in opioid peptide activity, and that these alterations may be useful in designing experimental therapeutic strategies in these conditions.     

Flight-correlated activity changes in neurons of the lateral accessory lobes in the brain of the locust Schistocerca gregaria

The study investigates activity changes in neurons of the lateral accessory lobes in the brain of the locust Schistocerca gregaria during wind-elicited tethered flight. Neurons with ascending projections from the ventral nerve cord to the lateral accessory lobes showed flight-associated excitations which were modulated in the flight motor rhythm. Descending neurons with ramifications in the lateral accessory lobes were tonically excited corresponding to flight duration. The onset of wind-elicited responses in the descending neurons preceded the onset of flight motor activity by 22–60 milliseconds. Neurons connecting the lateral accessory lobes with the central body, the anterior optic tubercles, or other brain areas showed a variety of responses including activity changes during flight initiation and flight termination. Activity in many of these neurons was less tightly coupled to the flight situation and often returned to background levels before flight was terminated. Most of the recorded neurons responded, in addition, to stationary visual stimuli. The results suggest that the lateral accessory lobes in the locust brain are integrative links between the central body, visual pathways, and the ventral nerve cord. The possible involvement of these brain areas in flight control is discussed.     

Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity.

In control rats small doses of apomorphine (25 to 100 μg/kg) decreased motor activity and reduced DOPAC content in the caudate nucleus. A larger dose (500 μg/kg) increased motor activity and elicited stereotypy. Chronic treatment with imipramine, amitryptiline and mianserine (10, 10 and 2.5 mg/kg twice daily for 10 days respectively) counteracted or reversed the effect of small doses of apomorphine on motor activity, left DOPAC content unchanged and potentiated the central stimulant response to the larger dose of apomorphine. Changes in apomorphine responses were observed after ten but not after two days of imipramine treatment and persisted unaltered up to 4 days after imipramine withdrawal. It is suggested that chronic treatment with antidepressants induces persistent subsensitivity in presynaptic dopamine receptors. The relevance of the findings in the therapeutic effect of these drugs is discussed.     

Evolution of behavior and neural control of the fast-start escape response

The fast-start startle behavior is the primary mechanism of rapid escape in fishes and is a model system for examining neural circuit design and musculoskeletal function. To develop a dataset for evolutionary analysis of the startle response, the kinematics and muscle activity patterns of the fast-start were analyzed for four fish species at key branches in the phylogeny of vertebrates. Three of these species (Polypterus palmas, Lepisosteus osseus, and Amia calva) represent the base of the actinopterygian radiation. A fourth species (Oncorhynchus mykiss) provided data for a species in the central region of the teleost phylogeny. Using these data, we explored the evolution of this behavior within the phylogeny of vertebrates. To test the hypothesis that startle features are evolutionarily conservative, the variability of motor patterns and kinematics in fast-starts was described. Results show that the evolution of the startle behavior in fishes, and more broadly among vertebrates, is not conservative. The fast-start has undergone substantial change in suites of kinematics and electromyogram features, including the presence of either a one- or a two-stage kinematic response and change in the extent of bilateral muscle activity. Comparative methods were used to test the evolutionary hypothesis that changes in motor control are correlated with key differences in the kinematics and behavior of the fast-start. Significant evolutionary correlations were found between several motor pattern and behavioral characters. These results suggest that the startle neural circuit itself is not conservative. By tracing the evolution of motor pattern and kinematics on a phylogeny, it is shown that major changes in the neural circuit of the startle behavior occur at several levels in the phylogeny of vertebrates.     

Neuromechanics: an integrative approach for understanding motor control

Neuromechanics seeks to understand how muscles, sense organs,motor pattern generators, and brain interact to produce coordinatedmovement, not only in complex terrain but also when confrontedwith unexpected perturbations. Applications of neuromechanicsinclude ameliorating human health problems (including prosthesisdesign and restoration of movement following brain or spinalcord injury), as well as the design, actuation and control ofmobile robots. In animals, coordinated movement emerges fromthe interplay among descending output from the central nervoussystem, sensory input from body and environment, muscle dynamics,and the emergent dynamics of the whole animal. The inevitablecoupling between neural information processing and the emergentmechanical behavior of animals is a central theme of neuromechanics.Fundamentally, motor control involves a series of transformationsof information, from brain and spinal cord to muscles to body,and back to brain. The control problem revolves around the specifictransfer functions that describe each transformation. The transferfunctions depend on the rules of organization and operationthat determine the dynamic behavior of each subsystem (i.e.,central processing, force generation, emergent dynamics, andsensory processing). In this review, we (1) consider the contributionsof muscles, (2) sensory processing, and (3) central networksto motor control, (4) provide examples to illustrate the interplayamong brain, muscles, sense organs and the environment in thecontrol of movement, and (5) describe advances in both roboticsand neuromechanics that have emerged from application of biologicalprinciples in robotic design. Taken together, these studiesdemonstrate that (1) intrinsic properties of muscle contributeto dynamic stability and control of movement, particularly immediatelyafter perturbations; (2) proprioceptive feedback reinforcesthese intrinsic self-stabilizing properties of muscle; (3) controlsystems must contend with inevitable time delays that can simplifyor complicate control; and (4) like most animals under a varietyof circumstances, some robots use a trial and error processto tune central feedforward control to emergent body dynamics.     

Neural correlates of flight activation and escape behavior in houseflies recovering from pyrethroid poisoning

Recovery from pyrethroid poisoning was studied in groups of adult female houseflies treated with LD50 doses of trans-permethrin or deltamethrin. The first overt sign of recovery was the appearance of normal posture, which was followed by jumping behavior and finally, coordinated flight when the flies had fully recovered. Prior to full recovery, treated houseflies were able to maintain normal posture and usually jump, but they could not fly. When tethered, these flightless houseflies responded to loss of tarsal contact by initiating normal patterned activity in the dorsolongitudinal flight muscles, yet the wings did not move. In flightless flies displaying jumping behavior, electrical stimulation of the brain evoked responses in the pleurosternal muscle, which controls thoracic tension during flight. Thus, many of the motor systems responsible for flight behavior seemed to be functional in flightless flies. Carbofuran, a carbamate anticholinesterase known to initiate spontaneous flight behavior from within the central nervous system, failed to elicit this response in flightless flies. These results suggested that the flightless condition was due to a disruption in central nervous pathways, and not to peripheral neuromuscular block. The pattern of recovery of different behaviors analyzed in this study was found to be consistent with the Jacksonian Hierarchy Principle, and the utility of this principle in guiding the design of new behavior-modifying compounds is discussed.     

Fast ballistic food-procuring movements in rats: Phenomenology and probable controlling mechanisms

Parameters of fast ballistic food-procuring movements were studied in albino rats. With the use of video and photorecording, the number of attempts used by an animal, to get the food globula, duration of the movements, and their phasic structure were analyzed within the whole learning period and certain experimental days. When the motor skill had been formed, programed ballistic components characterized by hard-to-modify parameters and components with a considerable impact of reverse afferentation in their formation and performance were analyzed. The experimental data are interpreted in terms of the expediency of using the operant motor reactions performed by rats getting food from a narrow manger as a model of voluntary motor activity in electrophysiological, behavioral, neurochemical, and morphological studies. The regularities in formation of motor programs, initiation, realization, and control of the movements, and central mechanisms of these phenomena are discussed.