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Myofascial pain syndrome caused by damage to the paravertebral muscles is considered as one of the causes of chronic back pain. At the same time, there is not enough information about the condition of the paravertebral muscles, and it is contradictory.The aim of the work is to elucidate the presence and severity of structural and functional changes in the paravertebral muscles and their role in the development of chronic nonspecific pain in the lower back in women.Material and methods. Morphological, immunohistochemical examination of a muscle tissue biopsy was performed in 17 patients aged 24 to 59 years (average age — 41.5 ± 12.1 years) with CNS (average duration of pain syndrome 10.0 ± 6.9 months) caused by myofascial pain syndrome, as well as determination by gel electrophoresis of the isoform composition of giant sarcomeric proteins titin and nebulin.Results. Morphological examination revealed no signs of necrosis, proliferation of connective and adipose tissue, inflammatory infiltration. The transformation of the myosin phenotype in the direction of an increase in the proportion of “fast” type II muscle fibers was revealed in the biopsies of the patients’ muscles. A decrease in the content of giant titin and nebulin proteins associated with myosin and actin in the sarcomere was also found.Conclusion. The data obtained indicate a violation of the contractile function of the paravertebral muscle in CNS.

The changes in the content of the giant sarcomeric cytoskeletal proteins titin (3000–3700 kDa) and nebulin (770 kDa) in skeletal muscles (m. soleus, m. gastrocnemius), and titin in the left ventricular myocardium, as well as of the submembrane cytoskeletal protein dystrophin (427 kDa) in m. soleus and m. extensor digitorum longus (EDL), have been studied in the edible dormouse Glis glis during hibernation. The animals were divided into two experimental groups: “Summer activity” and “Hypothermia”. It was found that the development of atrophic changes in the skeletal muscles of hibernating animals is accompanied by a decrease in the dystrophin content. Specifically, the fluorescence intensity in skeletal muscle cross sections labeled with primary antibodies to dystrophin and Alexa Fluor® 488 conjugated secondary antibodies decreased in animals of the “Hypothermia” group by 2.7 times (p < 0.05) and 2.0 times (p < 0.05) in m. soleus and m. EDL, respectively. SDS electrophoresis of proteins in agarose-strengthened macroporous 2.2%-polyacrylamide gel revealed an insignificant decrease (by 15%, p ≤ 0.01) in the titin content compared to the myosin heavy chain content in m. gastrocnemius of animals of the “Hypothermia” group. The titin content in m. soleus and cardiac muscle, as well as the nebulin content in m. soleus and m. gastrocnemius, did not decrease during hibernation. These results are consistent with our previous data for other hibernators: long-tailed ground squirrel, brown and Himalayan black bears. It can be assumed that during evolution, hibernating animals developed the molecular mechanisms responsible for maintaining a stable level of giant sarcomeric cytoskeletal proteins during hibernation.

Objectives. To study the structure and formation of Mauthner neuron dendrites in goldfish exposed to neurotoxic β-amyloid fragment 25–35 and prolonged sensory stimulation influencing the afferent inputs to these neurons. Materials and methods. Goldfish Mauthner neurons were studied by light and electron microscopy. Individual dendrites were identified, their volumes were determined, and synapse structure was assessed using virtual 3D images of Mauthner neurons obtained from serial sections of thickness 3 μm. The functional status of Mauthner neurons was evaluated indirectly from the motor lateralization of the fish. Results. Mauthner neurons responded to application of β-amyloid combined with subsequent prolonged sensory stimulation with decreases in the volume of the ventral dendrites, damage to their ultrastructure, and degeneration of a proportion of synapses. Degeneration of more active neurons was more significant than that of less active cells. Newly formed medial dendrites had greater volume and less damaged synapse ultrastructure than ventral dendrites. There were no differences in the sizes of specialized junctions between synapses of the same type on ventral and medial synapses. Conclusions. Medial dendrite formation is a compensatory reaction to dystrophy of the ventral dendrite due to the experimental treatment.

Objective : to assess the structural and functional state of skeletal muscles in the hip, as well as changes in the content of the sarcomere cytoskeleton proteins titin and nebulin and their phosphorylation level in patients with chronic alcohol intoxication. Patients and methods . Thirteen patients (4 men and 9 women; mean age, 38.9±9.9 years) with chronic alcohol intoxication were examined. The average duration of regular consumption of alcoholic beverages was 7.6±3.7 years. The mean amount of alcohol consumed per week was 48.2±13.1 units. A control group included 10 healthy volunteers matched for age and sex. A neurological examination was performed according to the generally accepted scheme. Laboratory tests involved blood biochemical analysis estimating the levels of liver enzymes, creatine phosphokinase (CPK), and insulin-like growth factor-1 (IGF-1). All the patients underwent hip magnetic resonance imaging (MRI), followed by assessment of the degree of muscle tissue damage and by determination of the volume of anterior and posterior thigh muscles. The content of titin and nebulin and their phosphorylation level were determined in the muscle tissue samples obtained by an open biopsy from the lateral head of the quadriceps femoris muscle. Results and discussion . Four (30.8%) patients were found to have proximal leg muscle weakness; the degree of paresis was the same in the anterior and posterior thigh muscles. There was a significant increase in the plasma level of liver enzymes; the CPK level remained within the reference values; there was a tendency towards lower IGF-1 levels. Analysis of MRI data showed that 7 (53.8%) patients had fatty degeneration in the thigh muscles. Quantitative evaluation ascertained a significant symmetrical decrease in the volume of anterior thigh muscles and a tendency towards a symmetrical reduction in that in the posterior thigh muscle compared to the control. Analysis of the content of titin and nebulin in the lateral head of the quadriceps femoris muscle revealed a significant decrease in the percentage of nebulin (81.1%; p < 0.01) and intact titin-1 (T1) isoforms (83.6%; p < 0.01). The percentage of proteolytic titin-2 (T2) fragments in the muscle of patients did not differ significantly from that in the control group. Estimating the phosphorylation level of the structural muscle proteins showed no significant differences when compared to the control. Conclusion . Anterior and posterior thigh muscle weakness should be considered as the main clinical manifestation of chronic alcoholic myopathy (CAM) in the absence of biochemical and neurophysiological markers of the disease. Lower extremity muscle MRI that can reveal a lower muscle volume concurrent with fatty degeneration is a non-invasive informative diagnostic technique for CAM. The pathogenesis of skeletal muscle atrophy in chronic alcohol intoxication involves the sarcomere structural proteins titin and nebulin, which regulate the interaction of the major contractile proteins actin and myosin, and whole muscle contraction.

—The effects of sensory stimulation on the model of paired Mauthner neurons of monocularly deprived goldfish have been studied by light- and electron microscopy. Three-dimensional reconstruction was performed using serial semi-thin sections in order to determine the volumes of soma and dendrites for the right and left Mauthner neurons. These data suggested that long-term stimulation of some fish caused a decrease in the volume of the lateral dendrites of neurons contralateral with respect to the side of the enucleated eye. As a result, the morphological homeostasis in the dendrites of Mauthner neurons, which was observed in the control fish, was disturbed after the effect of stimulation upon this group of fish. The main mechanism of this effect of stimulation, according to ultrastructural analysis, is the compaction of the cytoskeleton in the lateral dendrite of a neuron and a reduction in the number of synaptic vesicles in the region of afferent synapses. In contrast, stimulation of the remaining fish induced the resistance of the contralateral Mauthner neuron to prolonged stimulation, as well as the hypertrophy of its lateral and shortening of the ventral dendrites. These results suggest that the homeostasis of the dendrites of Mauthner neurons essentially depends on the state of the visual inputs, the load on which increased as a result of the doubled impact.

Molecular mechanisms underlying muscle-mass retention during hibernation have been extensively discussed in recent years. This work tested the assumption that protein synthesis hyperactivation during interbout arousal of the long-tailed ground squirrel Urocitellus undulatus should be accompanied by increased calpain-1 activity in striated muscles. Calpain-1 is known to be autolysed and activated in parallel. Western blotting detected increased amounts of autolysed calpain-1 fragments in the heart (1.54-fold, p p p p

During spaceflight and immediately after it, adaptive neuroplastic changes occur in the sensorimotor structures of the central nervous system, which are associated with changes of mainly vestibular and visual signals. It is known that the movement of the eyeball in the vertical direction is carried out by muscles that are innervated by the trochlear nerve (CN IV) and the oculomotor nerve (CN III). To elucidate the cellular processes underlying the atypical vertical nystagmus that occurs under microgravity conditions, it seems necessary to study the state of these nuclei in animals in more detail after prolonged space flights. In this work, we carried out a qualitative and quantitative light-optical and ultrastructural analysis of the nuclei of the trochlear nerve in mice after a 30-day flight on the Bion-M1 biosatellite and followed by a stay for 13-14 hours under the influence of the Earth’s gravity after landing. As a result, it was shown that the motoneurons in the nucleus of the trochlear nerve changed their morphology under the influence of microgravity. Cell nuclei of the motoneurons had a more simplified rounded shape than in the control. In addition, the dendrites of these motoneurons significantly reorganized geometry and orientation under microgravity conditions; the number of dendritic branches has been increased to enhance the reduced signal flow. Apparently, to ensure such plastic changes, the number and size of mitochondria in the soma of motoneurons and in axons coming from the vestibular structures increased. In addition, the experimental animals showed an increase in the size of the cisterns of the rough and smooth endoplasmic reticulum in comparison with the control group of animals left on Earth, for which the environmental conditions in the spacecraft were reproduced. Thus, the main role in the adaptation of the trochlear nucleus to microgravity conditions, apparently, belongs to the dendrites of motoneurons, which rearrange their structure and function to enhance the flow of sensory information. These results are useful for the development of new, more effective means to facilitate the stay and work of space travelers in a long spaceflight.

The effects of the Thr–Ser–Lys–Tyr peptide, which was shown to display neuroprotective activity in cell cultures in vitro, were studied in the model of paired Mauthner cells of goldfish. It was found that intracerebral injections provided the peptide to be applied into the zone of the right Mauthner cell under the fourth ventricle of the hindbrain lead to a dose-dependent decrease in the number of spontaneous turns of the goldfish to the left. It was shown that this effect is not eliminated under long-lasting optokinetic stimulation when the fish instinctively follow stimuli with a low spatial frequency that are moving in the nasal-to-temporal direction. We used the method of three-dimensional reconstruction by serial histological sections to study the dendrite morphology of the Mauthner cells in control and experimental goldfish. It was found that optokinetic stimulation of control goldfish evokes the dystrophy of the ventral dendrite of the right Mauthner cell, which is the target of this type of stimulation. Conversely, the peptide stabilize the size of the ventral dendrite of the right Mauthner cell under stimulation. These data could be interpreted as evidence of the neuroprotective effect of the Thr–Ser–Lys–Tyr peptide in vivo.

Mauthner neurons in goldfish fry were studied by the methods of light and electron microscopy. The structure and volume of individual dendrites as well as the structure of axodendritic synapses were examined using virtual images of neurons formed from serial 3-μ sections. In short-time (5 h) experiments with application of dopamine, β-amyloid fragment (25-35), and long-term sensory stimulation affecting afferent inputs to Mauthner neurons, the dendrites were larger than the same dendrites under the same conditions without dopamine application. Application of dopamine induced no pathological changes in the structure of axodendritic chemical and electric synapses containing desmosome-like contacts.

Morphometric methods were used to study the ultrastructure of afferent synapses on the ventral dendrites of Mauthner neurons (MN) during adaptation of goldfish to prolonged, fatiguing, sensory (visual) stimulation inducing increased resistance of MN. The extent of active zones (AZ) in synapses located on the MN ventral dendrite was found to decrease significantly, by 23%, after adaptation. The extent of the AZ of excitatory visual synapses decreased by 29% as compared with controls, with a simultaneous 71% increase in the extent of desmosome-like contacts (DLC) bordering AZ. There was also a 19% reduction in the extent of AZ of inhibitory synapses after adaptation, which is consistent with the important role of inhibitory processes in sensory pathways during memory formation. Considering the actin nature of DLC, it can be suggested that adaptation to visual stimulation is based on a synaptic mechanism of regulation of neurotransmitter secretion by actin.

We studied the correlation between functional activity and 3D structure of Mauthner neurons (MNs) of the goldfish in the norm, after isolated application of an aggregated fragment of beta-amyloid 25-35 (Aβ25-35), and a combination of such application with optokinetic stimulation of the fish. It was shown that the clear correlation between the structure and function of MNs observed in the control is strongly disturbed after the action of beta-amyloid aggregates. According to the data of ultrastructural analysis, destruction of the cytoskeleton, vacuolization of the MN cytoplasm, and depletion of the vesicular apparatus of afferent synapses are the main events responsible for such effect of Aβ25-35. Fatiguing sensory optokinetic stimulation of fishes applied against the background of action of Aβ25-35 induces dystrophy of the ventral MN dendrites and the formation, near the latter, of earlier absent hypertrophied medial dendrites; these dendrites were comparable in their dimension with the main MN dendrites in control fishes. The data obtained allow us to suppose that a traumatic mechanical influence of the beta-amyloid aggregates on neurons and their processes is an important factor in the development of amyloidosis-related neurodegenerative diseases, and destruction of the cytoskeleton is one of the key phenomena from this aspect.

Immunogold labeling was used to identify serotoninergic synapses of the chemical and mixed types on the ventral dendrite (VD) of Mauthner neurons (MN) in goldfish. These had the characteristic feature that they contained several mitochondria in the bouton and, apart from an active zone (AZ), had an obligatory desmosome-like contact (DlC). The AZ of these synapses generally contacted unlabeled chemical crested synapses, which in turn interacted directly with the VD. These latter synapses had virtually no mitochondria and lacked a DlC, such that they could be identified as inhibitory. This “two-level” organization of excitatory serotoninergic and inhibitory synapses appears to be directly related to the reciprocal mechanism regulating the functional activity of MN via the visual apparatus.

Goldfish are known to exhibit motor asymmetry due to functional asymmetry of their Mauthner neurons that induce the turns to the right or left during free swimming. It has been previously found that if the less active neuron is subjected to prolonged aimed visual stimulation via its ventral dendrite, the motor asymmetry of goldfish is inverted, testifying that this neuron becomes functionally dominant, while the size of the ventral dendrite under these conditions is reduced 2-3 times compared to its counterpart in mirror neuron. Earlier it has been also revealed that training optokinetic stimulation induces adaptation, a substantial resistance of both fish motor asymmetry and morphofunctional state of Mauthner neurons against prolonged optokinetic stimulation. The aim of this work was to study the cellular mechanisms of the effect of an unusual visual afferent input on goldfish motor asymmetry and Mauthner neuron function in norm and under adaptation. It was shown that serotonin applied onto Mauthner neurons greatly reduces their activity whereas its antagonist ondansetron increases it. Against the background of visual stimulation, serotonin strengthens functional asymmetry between neurons whereas ondansetron smoothes it. Taken together these data suggest the involvement of serotonergic excitatory synaptic transmission in the regulation of Mauthner neurons by vision. Ultrastructural study of the ventral dendrites after prolonged optokinetic stimulation has revealed depletions of numeral axo-axonal synapses with specific morphology, identified by means of immunogold label as serotonergic ones. These latter in turn are situated mainly on shaft boutons, which according to specific ultrastructural features are assigned to axo-dendritic inhibitory synapses. Thus, the excitatory serotonergic synapses seem to affect Mauthner neuron indirectly through inhibitory synapses. Further, it was morphometrically established that adaptation is accompanied by the significant decrease of active zones dimensions in both serotonergic and inhibitory synapses. Finally, it was determined in model experiments that the interaction of globular actin with glycine, a main inhibitory neurotransmitter supposedly directly and chronically affecting the ventral dendrite, results in actin filaments formation. It is assumed that glycine-induced cytosolic actin polymerization is a cause of reduction in the ventral dendrite size under stimulation. Thus, it was established that a rather small group of synapses situated on an individual dendrite of the neuron determines the execution of the important form of animal behavior.

The effects of training with adaptive vestibular stimulation on the function and three-dimensional structure of Mauthner neurons (MN) were studied in goldfish with experimental amyloidosis induced by application of aggregated β-amyloid protein (Aβ25–35). In comparison with controls, adapted MN acquired significant resistance to Aβ25–35. Considering the key role of dopamine in the adaptation of MN to sensory stimuli, its actions on the development of an amyloidosis model were studied; the results showed that application of dopamine to MN, like increases in the dopamine concentration induced by L-DOPA, was followed by protection of MN structure and function from the pathogenic actions of Aβ25–35. Electron microscopic studies showed that the protective action of dopamine on neurons can be explained in terms of its ability to dissociate β-amyloid polymers into short inactive fragments.

Previous studies have shown that contralateral (to the preferred turning side) optokinetic stimulation and ipsilateral enucleation of the eye lead to significant (by a factor of 2–4) decreases in the volume of the ventral dendrite (VD) in one of the two Mauthner neurons (MN) of the goldfish, which becomes functionally more active. We report here our studies of MN ultrastructure after these unilateral influences from the visual system. In both cases, the whole length of the shrunken VD showed emptying of synapses and compaction of its cytoskeleton as compared with the cytoskeleton of the VD of the contralateral MN and the cytoskeleton of the lateral dendrites and bodies of both neurons. It is suggested that emptied synapses are part of the excitatory visual input and that the control of the functional activity of MN via VD involves both cytoskeletal and synaptic mechanisms.

Three-dimensional reconstruction was used to study the structural correlates of significant increases in the activity of Mauthner neurons (MN) deafferented after unilateral enucleation of the eye evidenced by an irreversible shift in motor asymmetry in goldfish towards the “blind” side. The results showed that in some cases, the dominance of the MN correlated significantly with a decrease in the volume of its ventral dendrite, while in others, it correlated with an increase in the sizes of the body and the lateral dendrite. Both structural signs appeared to result from local redistribution of the neurotransmitter balance due to the tension of the undamaged sensory inputs. Overall, the results demonstrated that prolonged adaptive changes in the behavior of the fish may be regulated by specific morphological rearrangements of MN at the level of individual dendrites acting via feedforward and feedback mechanisms.

We studied the effects of unilateral enucleation of the eye on the motor asymmetry of goldfish fries and morphometric characteristics of their Mauthner neurons, MNs (data of 3D reconstruction using serial slices). Enucleation of the right or left eye in ambidextral fishes resulted in stable preference of turnings during swimming toward the side of visual deafferentation and in a shift of the initial motor asymmetry coefficient (MAC) by 25%, on average. Ipsilateral enucleation of the eye in dextral and sinistral fishes intensified the initial motor asymmetry by 20%. Contralateral enucleation of the eye in dextral and sinistral fishes induced inversion of the motor asymmetry with a decrease in the MAC by 50%, on average. All operated fishes stably (within 3 months or more) preferred to turn toward the side of the enucleated eye. Morphological measurements showed that the size of the ventral dendrite of the MN contralateral with respect to the side of enucleation noticeably decreased. At the same time, this neuron (according to a shift in the motor asymmetry of the fish) became the functionally dominant unit. These data agree with the earlier supposition on a reciprocal relation between the level of functional activity of the MN and the size of its ventral dendrite. Selective changes in the dimension of the ventral dendrite of the MN receiving visual inputs probably resulted from the action of some endogenous trophic factor. The effect of this factor was enhanced after enucleation of the eye and the corresponding dysfunction of the contralateral visual input. A specific local change in the balance of neurotransmitter influences upon the MN ventral dendrite can play the role of such a factor. From the neurophysiological aspect, a decrease in the size of the ventral MN dendrite is a primary link in the chain of events resulting in modification of behavior; it leads to intensification of the integral functional activity of the MN and a shift of the motor asymmetry of the fish compensating, in such a way, the effect of unilateral visual deprivation.

Adaptation as a memory model appears, at the cellular level, as an increase in the resistivity of neurons to fatigue under the influence of repetitive natural training stimulation. Selective induction of adaptational changes in separate compartments of one and the same neuron can also serve as an important instrument for identification of the roles of these compartments in the integrative function of the individual neuron. Mauthner neurons (MNs) of fishes (the goldfish in particular) possess a clearly differentiated soma and two dendrites, lateral and ventral ones. The soma and lateral dendrite of each MN receive afferentation from the ipsilateral vestibular apparatus; at present, the functional and morphological aspects of selective adaptational modifications induced in these compartments by adequate vestibular stimulation have been examined in detail. As to the ventral MN dendrite receiving visual afferentation from the contralateral eye via the ipsilateral tectum, it remained impossible until now to realize the respective approach. We found that training sessions of visual optokinetic stimulation performed in certain modes provide selective activation of one MN through its ventral dendrite and increase the resistivity of this cell to fatiguing stimulation. Therefore, we first demonstrated the possibility of adaptational changes in an individual ventral dendrite of the MN. If fishes were preliminarily adapted with respect to vestibular stimulation, and the resistivity of the soma and lateral dendrite was selectively increased, the resistivity to fatiguing visual test stimulation also increased. On the other hand, if fishes were preliminarily adapted with respect to visual stimulation, the resistivity to fatiguing vestibular stimulation also increased. The observed increase in the resistivity of MNs of fishes adapted due to sensory stimulation of one afferent input with respect to sensory stimulation of other sensory input, as well as an increase in the resistivity to sensory stimulation of one modality, probably show that the mechanism of increase in the resistivity is the same in both cases.

In goldfishes, we studied (i) manifestations of functional activity of Mauthner neurons (MNs) reflected in motor behavior and (ii) changes in 3-D morphometry (ratio of volumes) and ultrastructure of MNs after applications of an actin-polymerizing peptide obtained from scorpion venom and after vestibular rotational stimulations (trainings) inducing natural modification of functions of the MNs (adaptation). In MNs subjected to application of the peptide, the increase in the functional resistance and morphological stability caused by long-lasting stimulation directly depended on the dose of the applied peptide or on the effectiveness of trainings, whereas in intact and control MNs such stimulation resulted in significant decreases in the activity and volumes of these cells. At the ultrastructure level, both applications of the peptide and trainings caused the formation of extensive bundles of actin filaments (“stress-fibers”) in the cytoplasm of MNs and led to an increase in the dimension of desmosome-like contacts (DLCs) in afferent synapses. At chemical synapses, the effect looked like a reciprocal decrease in the length of the active zones (a structural sign of long-term depression, LTD), while at mixed synapses this was manifested in an increase in the number of fibrillar bridges in the gaps of DLCs (a structural sign of long-term potentiation, LTP). The data obtained allow us to hypothesize that LTD of the efficacy of transmission through chemical synapses is involved in the formation of the adaptation state of the MNs and that polymerization of actin in the cytoplasm and DLCs underlies the mechanism of LTD and adaptation. The development of ultrastructural manifestations of LTP at mixed synapses after polymerization of actin by the peptide, which is related to a reciprocal increase in the efficacy of “mixed” afferent inputs, explains the maintenance of a high integral level of activity of the MNs, despite a drop in the functional activity of “ chemical” afferent inputs. Therefore, the actin cytoskeleton plays a clearly significant role in the maintenance of the balance of excitation at the neuronal level.

In the goldfish, we studied the effects of intramedullar applications of glutamate (Glu), dopamine (DA), and of long-lasting rotational stimulation on the functional activity, dimensional characteristics, and ultrastructure of Mauthner neurons (MNs). Applications of Glu, especially when combined with rotational stimulation, were found to result in suppression of the function of MNs, in a decrease in their dimensions and lengths of desmosome-like contacts (DLCs, whose structure is determined by filamentous actin) in afferent mixed and chemical synapses, and in destruction of actin microfilaments in the cytoskeleton of MNs. Applications of DA, vice versa, induced an increase in the resistance to the effects of long-lasting stimulation and stabilized the dimensions of MNs; the length of DLCs increased in afferent synapses of both the above types, and the number of fibrillar actin bridges in the DLC cleft of mixed synapses also increased. Bundles of the actin filaments, which were preserved after stimulation, appeared in the cytoskeleton of MNs. Testing of the action of neurotransmitters on actin preparations in vitro showed that Glu entirely depolymerizes filamentous actin, while DA, vice versa, polymerizes monomeric actin. Thus, the Glu-and DA-induced reactions are similar in their types and are of a reciprocal nature both in the actin cytoskeleton of MNs in situ and in purified actin in vitro; these effects correlate with suppression of the functional state of MNs under the influence of Glu and with stabilization of this state under the influence of DA. These results agree with the concept on the roles of depolymerization and polymerization of actin in changes of the morphofunctional state of MNs and show that actin of the cytoskeleton of MNs is a cellular target for the actions of Glu and DA. The similarity between the effects of tested neurotransmitters on actin in MNs in situ and in cell-free preparations in vitro allows us to hypothesize that these transmitters can penetrate into the neuron.

We examined the morphological peculiarities of Mauthner neurons, MNs, in goldfishes with a phenotypically different or an experimentally modified preference to perform rightward vs leftward turnings in the course of motor behavior; this preference was characterized by values of the motor asymmetry coefficient (MAC). 3D reconstruction of MNs was performed based on several histological sections; volumes of the soma, lateral and ventral dendrites (LD and VD, respectively), initial segment of the axon, as well as full volumes of the right and left neurons, were calculated. Differences between the above parameters were expressed as structural asymmetry coefficients (SACs). It was shown that clear orientation asymmetry of motor behavior of the fish is accompanied by differences in the dimensions of MNs and their compartments; MNs localized contralaterally with respect to the preferred turning side were considerably bigger than ipsilateral neurons. Experimental influences inducing inversion of the motor asymmetry of fishes inverted structural asymmetry of their MNs. In fishes with no phenotypical preference of the turning side and in individuals whose motor asymmetry was smoothed due to experimental influences (rotational stimulations), structural asymmetry of the MNs was also smoothed. Changes of the structural proportions developed, as a rule, due to decreases in the dimensions of one or both MNs and their compartments. The MAC value was in direct correlation with the value of SAC of the MNs and with values of this coefficient for the soma and the sum soma + LD. At the same time, reciprocal relations were found for the MAC and structural asymmetry of the VD; the decrease in the volume of VD was related to an increase in the preference of the contralateral turning side by the fish, and vice versa. In general, the results of our study demonstrate that both morphological and functional peculiarities of MNs correlate to a significant extent with such a form of motor behavior of fishes as realization of spontaneous turnings.

We studied changes in the motor asymmetry of the goldfish induced by single-session long-lasting vestibular stimulations (clockwise and counter clockwise rotations around the rostro-caudal body axis) and repetitive everyday short sessions of such stimulation (training); the latter mode led to the development of adaptation (resistance to fatigue). Rotational stimulation of different durations and directions elicited effects of different patterns and intensities. Such stimulation enhanced or, vice versa, smoothed the motor asymmetry in “dextral” and “ sinistral” fishes, up to full symmetry or even a change of the preferred turning direction. Adaptation to unilateral rotational stimulation allows an experimenter to selectively and gradually induce the resistivity of the left-or right-ward asymmetry to fatigue effects. Earlier, we found that the motor asymmetry in the goldfish, which is determined by the functional asymmetry of the brain, correlates with the morphological asymmetry of Mauthner neurons localized in the medulla in a mirror manner and playing a crucial role in the control of turnings in the course of locomotion (swimming). Experimental rotational stimulation-induced gradual modification of the motor asymmetry in the goldfish can serve as a physiological model for more detailed studies of the structural base of the functional brain asymmetry and some mechanisms of adaptation on the level of single neurons.

We studied swimming of goldfish fries about 3 cm long in a narrow channel by calculating the numbers of spontaneous turns on different sides. The ratio of fishes preferring to turn to the right vs to the left was 1.5:1.0, respectively; two-thirds of the fishes demonstrated an ambilateral behavior. Experiments with compulsory 10-min-long rotation of the fishes (clockwise around the longitudinal body axis for fishes preferring right-side turns and anticlockwise for fishes preferring left-side turns) showed that the behavioral asymmetry smoothed somewhat after such a procedure, and a greater number of the fishes became ambilateral in their preference to turn to one side or another. After a one- or two-day-long test, the initial asymmetry of motor behavior completely recovered. Compulsory rotation of similar fishes in the opposite direction exerted no influence on the asymmetry in the choice of the turning direction. Adaptation-induced training of the fishes (using fatiguing long-lasting vestibular stimulation) resulted in some smoothing of motor asymmetry but did not change its general pattern. Thus, our findings allow us to believe that a noticeable proportion of the goldfish individuals (similarly to other animals and humans) is characterized by an innate asymmetry of the motor function with a clear preference for either right- or left-side turnings. These relations can be smoothed under experimental influences but are recovered later on, i.e., they are stable and are not fundamentally transformed. We assume that the asymmetry of motor behavior of fishes in a narrow channel can be an adequate pre-requisite for further examination of the asymmetry of the brain and motor centers controlling changes in locomotion (body turnings)

The structural mechanisms that control the neuronal functional activity maintaining the brain functional asymmetry were studied using the relationship between the function and structure of goldfish Mauthner neurons (MNs) responsible for fish motor asymmetry as a model. It was shown for the first time that the dominant activity in one of the two counter neurons symmetrically situated in the medulla oblongata directly correlates with changes in its integral volume and is inversely regulated by the size of its ventral dendrite. It is known that the variability of the neuron dimensions is due to changes in the actin component of the cytoskeleton. The experimental data presented are discussed in terms of the involvement of cytosol actin in the control of the volume of somata and the main dendrites of MNs with the participation of dopamine and glutamate, two major neurotransmitters that are known to regulate the function of MNs.

The effects of applying aggregated beta-amyloid peptide fragment 25-35 on the three-dimensional structure and volume of Mauthner neurons (MN) and on motor asymmetry were assessed in goldfish using reconstructions based on serial histological sections. These experiments showed that the motor asymmetry of the fish was stable in the intact state and in controls and correlated tightly with structural asymmetry of neurons. beta-Amyloid produced large changes or inversion in motor asymmetry, which did not coincide with or even contradicted the structural asymmetry of MN. This occurred as a result of marked dystrophy or, conversely, hypertrophy of individual neurons and their individual dendrites, with changes in their proportions. It is suggested that the harmful action of beta-amyloid on MN structure and the discordant ("incorrect") behavior of the fish may result from mechanical deformation evoked by its tape-like fibrils. Overall, the results lead to the conclusion that MN provide a suitable system for studying the structural aspects of amyloidosis.

We have previously shown that contralateral optokinetic (visual) stimulation (COS) evokes inversion of motor asymmetry in goldfish and three-fold reductions in the volume of the ventral dendrite of the ipsilateral Mauthner neuron (MN). A training regime consisting of repeated daily sessions of COS induced resistance of the motor behavior of the fish to this treatment. We report here our studies of the effects of training sessions of COS on the structure of MN and their components. Daily visual training was found to stabilize the sizes of the dorsal dendrites of MN, significantly increasing their resistance to single prolonged sessions of COS. Thus, repeated stimulation of an individual dendrite induces an adaptive morphological state in the dendrite and in the neuron as a whole. This allows more detailed studies of the role of the individual dendrite in modifying the functional activity of the whole neuron in the mechanisms of adaptation and memory at the cellular level to be performed.

Recent studies have established that following an optomotor drum rotating in the direction contralateral to that spontaneously preferred by goldfish fry inverts their motor asymmetry. Studies of the structure of Mauthner neurons (MN) using the histological technique of three-dimensional reconstruction along with measurement of the volumes of the right and left MN in these fish showed that the ipsilateral MN underwent a three-fold reduction in the volume of the ventral dendrite (VD), which was in inverse proportion to the functional activity of the MN. The total volume of the contralateral MN was 25% larger than the volume of the ipsilateral MN, the situation typical of intact fish. It is suggested that the decreases in the size of the VD receiving afferentation from the contralateral eye, which follows the moving band of the optomotor drum, results from the specific contralateral visual stimulation, and is the first evidence of the possible natural stimulation of the MN via the VD.

Three-dimensional computer reconstruction working from serial histological sections was used to study the morphology of the right and left Mauthner neurons (MN) in goldfish fry showing marked preferences to turn stably to the right or left in a narrow water channel or showing no asymmetry in their choice of side during turns. Visually, fish with left-sided motor asymmetry had larger MN on the right side, while fish with right-sided motor asymmetry had larger MN on the left side. Fish with symmetrical turns to the right and left showed no differences in MN size. Quantitative assessment of the MN of fish with preferences for turns to one side or the other revealed significant differences in the sizes of the somatic part, the axon hillock, and the axons of neurons located on the contralateral side of the medulla oblongata. Analysis of the statistical relationships between the functional (motor) asymmetry of fish and the morphological asymmetry of the somatic parts of MN in the same fish revealed a stable correlation (0.69) between these measures. Given that MN initiate unilateral turns of the body in free movement, the data obtained here lead to the conclusion that the larger neuron is more frequently activated in natural conditions as compared with the smaller, contralateral, neuron.