Dopamine Improves Resistance of Dendrites of Mauthner Neurons to Destruction Induced by Sensory Stimulation and Application of Β-Amyloid.

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, ß-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.

[Ultrastructure of afferent synapses on the ventral dendrite of mauthner neurons after goldfish adaptation to optokinetic stimulation].

Using the morphometric techniques, the ultrastructural changes of the afferent synapses on the ventral dendrite of the Mauthner neurons (MNs) were studied after the adaptation of goldfish to long-term fatiguing sensory (visual) stimulation, characterized by the growth of MN resistance. It was shown that after the adaptation, the length of active zones (AZs) in the synapses located on the MN ventral dendrite was significantly reduced by 23%. At the same time, the length the AZs of the excitatory visual synapses was reduced by 29% in comparison with the control, while the length of desmosome-like contacts (DLCs) bordering AZs was increased by 71%. It was also found that the length of AZs in the inhibitory synapses was decreased by 19% after the adaptation, which is consistent with the important role of inhibitory processes in the sensory pathways during the memory formation. Taking into account the actin nature of the DLCs, the basis of the adaptation to the visual stimulation is suggested to be in the presynaptic mechanism of neurotransmitter secretion regulation by actin.

[Serotoninergic synapses on the ventral dendrite of the mauthner neuron (ultrastructural study with immunogold labeling)].

Using immunogold labeling, excitatory serotoninergic synapses of both chemical and mixed types, were found on the ventral dendrite (VD) of goldfish Mauthner neuron (MN).They are characterized by the presence of several mitochondria in the bouton and by an obligatory desmosome-like contact (DLC) besides the active zone (AZ). Their AZs were commonly found to make contact with the unlabeled chemical crested synapses, which, in turn, directly interacted with VD. These synapses were practically devoid of mitochondria and had no DLCs, thus allowing to identify them as the inhibitory ones. This "two-level" organization of excitatory serotoninergic and inhibitory synapses appears to be related to the reciprocal mechanism of the regulation of MN functional activity by visual input.

[Induction of neuron morphological resistance to beta-amyloid].

The effect of training adaptive vestibular stimulations on goldfish Mauthner neurons (MN) function and three-dimensional morphology was studied in experimental amyloidosis caused by application of aggregated beta-amyloid protein (Abeta25-35). It was found that as compared with control, adapted (trained) MN gained significant resistance to Abeta25-35. Taking into consideration the key role of dopamine in MN adaptation to sensory stimulations, its effect on the development of model amyloidosis was studied. It was shown that the application of dopamine onto MN as well as the increase of its concentration in brain by means of L-dopa protected MN structure and function against pathogenic influence of Abeta25-35. Using electron microscopy it was shown that dopamine protective action on neurons was due to its ability to dissociate polymer amyloid molecules into short inactive fragments.

[Ultrastructure of Mauthner neurons after optokinetic stimulation and eye enucleation].

It was previously shown that the contralateral (relative to preferred side of turns) optokinetic stimulation and ipsilateral eye enucleation cause a significant, 2- to 4-fold reduction of the ventral dendrite (VD) volume in one of two goldfish Mauthner neurons (MN) that becomes more active functionally. In this study, we investigated the MN ultrastructure after mentioned unilateral visual effects. In both cases, devastation of the afferent synapses was detected along the full length of the reduced VD, with simultaneous compaction of its cytoskeleton, in contrast to those of VD of the contralateral MN and of lateral dendrites and cell bodies of both neurons. It is suggested that the depleted synapses belong to the excitatory visual afferent input, and both cytoskeletal and synaptic mechanisms are involved in the regulation of MN functional activity through VD.

Morphofunctional changes in goldfish Mauthner neurons after application of beta-amyloid.

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.

Stabilization of mauthner neuron structure on adaptation of goldfish to contralateral optokinetic stimulation.

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.

[Correlation between the sizes of the individual parts of goldfish Mauthner neuron and its integral function after eye enucleation].

Using the method of 3D reconstruction, the structural correlates of significantly increased functional activity of denervated Mauthner neuron (MN) were studied after the unilateral eye enucleation, that resulted in the irreversible shift of the goldfish motor asymmetry to a "blind" side. It was established that in some cases the functional dominance of MN was significantly correlated with the reduction of the volume of its ventral dendrite, while in the other cases it was correlated with the increase in sizes of its soma and the lateral dendrite. Both structural features, probably, were caused by local redistribution of the neurotransmitters due to the stress of sensory inputs that remained undamaged. Thus, it was demonstrated that the prolonged adaptive changes in goldfish behavior could be regulated by means of specific morphological reorganizations of MN at the level of their individual dendrites by the principle of feedback or feedforward mechanisms.

[Stabilization of mauthner neuron structure in goldfish adapted to the contralateral optokinetic stimulation].

Previously we have demonstrated, that the contralateral optokinetic (visual) stimulation (COS) induces an inversion of goldfish motor asymmetry and three-fold decrease of the ventral dendrite of ipsilateral Mauthner neuron (MN) volume, whereas repetitive in training mode daily COS sessions induced a motor behavior resistance to this influence in fish. In the present investigation we have examined the effect of the training COS sessions on the structure of MN and their parts. It was found that daily visual training stabilizes the size of the ventral dendrites, significantly increasing their resistance to single prolonged COS. Thus, the adapted morpho-functional state was induced in the individual dendrite and in the whole neuron by repetitive stimulation of that dendrite. These results make it possible to investigate in more detail the role of an individual dendrite in the modification of functional activity of the whole neuron and in adaptation and memory mechanisms at the cellular level.

[Morpho-functional changes in the goldfish Mauthner neurons after beta-amyloid application].

The influence of aggregated beta-amyloid peptide fragment 25-35 application on three-dimensional structure and volume of Mauthner cells (MCs), as determined by reconstruction from serial histological sections, and on goldfish motor asymmetry was studied. It was shown that in intact and control goldfish motor asymmetry was stable and strongly correlated with structural asymmetry of neurons. But under the influence of beta-amyloid, motor asymmetry appeared to be strongly changed or inverted, did not correlate with structural asymmetry and frequently even was opposite to it. This resulted from strong dystrophy or, on the contrary, hypertrophy of individual neurons and their separate dendrites with the change in the proportions between them. It is suggested that injurious effect of beta-amyloid peptide on MCs structure, discordant with ("irregular") fish behavior, could be the result of mechanical deformation, induced by ribbon-like fibrils of amyloid peptide. These findings collectively suggest that MCs are the adequate object for the study of the structural aspects of amyloidosis.

Changes in the ventral dendrite of Mauthner neurons in goldfish after optokinetic stimulation.

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.

[Changes of the ventral dendrite of a goldfish Mauthner neurons induced by optokinetic stimulation].

It was recently demonstrated that following the optomotor drum, rotating contralaterally to the turn side, spontaneously preferred by the goldfish fry, inverted their motor asymmetry. The study of Mauthner neuron (MN) structure using the histological method of 3D reconstruction, and the measurements of right and left MN in these fishes, has detected the 3-fold decrease of the volume of the ventral dendrite (VD) of ipsilateral MN, which was reciprocally related to MN functional activity. At the same time, total volume of contralateral MN remained larger than that of ipsilateral one by one quarter, which was the case in intact fishes. It is suggested that the decrease in the size of VD, which receives the afferentation from the contralateral eye, that follows the moving stripes of the optomotor drum, is the result of a specific contralateral visual stimulation and is the first evidence of the possibility of MN natural stimulation through VD.

Correlation between the sizes of Mauthner neurons and the preference of goldfish to turn to the right or left.

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.

[Correlation of the sizes of Mauthner neurons with the preference in the goldfish to turn rightwards or leftwards].

Using the three-dimensional computer reconstruction from serial histological sections, the morphology of right and left Mauthner cells (MC) was examined in the goldfish fry which demonstrated clearly pronounced preference to turn to the right or to the left in a narrow water channel or which did not show any asymmetry in choosing the side of turning. Visually, the goldfish with left-sided motor asymmetry seemed to possess larger right MC, while in the goldfish with right-sided motor asymmetry left MC were larger. In fish with symmetric proportion of right or left turnings, the sizes of MC did not differ. Quantitative evaluation of MC in fish showing the preference of turning side has revealed significant differences in the sizes of cell bodies, axon hillock and axons of MC, located contralaterally in medulla oblongata. Analysis of a statistic relations between functional (motor) and morphological asymmetry of MC cell body in the same fish indicated the existence of a stable correlation (0,69) between them. Taking into consideration that MC initiate unilateral body turn during free swimming of fish, it may be concluded that the larger size of neuron predetermines its more frequent natural activation in comparison with the contrlateral neuron, that has smaller size.