Number Of Axodendritic Synapses Research Articles

Morphological changes in motoneurons of the oculomotor nucleus of mice after a 30-day space flight and through a 7-day period of readaptation to earth gravity.

The cellular mechanisms of neuroplastic changes in the structure of motoneurons and neuropils of the oculomotor (III) nuclei in mice after a 30-day space flight and 7 days after landing were studied. The results showed that microgravity caused degenerative phenomena in neurons: a decrease in the number of terminal dendritic branches was found both after flight and after readaptation to Earth's gravity. In mice after the flight, the number of axodendritic synapses was less than in the control, and their number was not restored after the readaptation. The number of mitochondria in the motoneurons of animals after the flight also decreased and after the readaptation reached only the control value. In addition, a significant number of dark motorneurons were found in mice after readaptation, which indicates that degeneration was caused not only by microgravity, but also by a reaction to the landing of the biosatellite. On the contrary, in the trochlear nucleus, as we showed earlier (Mikheeva et al. in Brain Res 15(1795):148077. https://doi.org/10.1016/j.brainres.2022.148077 , 2022), after readaptation, the dendrites and synaptic contacts were restored, and mitogenesis is significantly enhanced. It has been suggested that morphological changes in the oculomotor nucleus may be the main cause of microgravity-induced nystagmus.

Studying the structure of the nucleus of the trochlear nerve in mice through 7 days of readaptation to earth gravity after spaceflight

The negative effect of hypogravity on the human organism is manifested to a greater extent after the astronauts return to the conditions of habitual gravity. In this work, to elucidate the causes underlying atypical nystagmus, arising after the flight, we studied structural changes in the motoneurons of the trochlear nerve after a 7-day readaptation of mice to the conditions of Earth's gravity. It is known, that motoneurons of the trochlear nerve innervate the muscle that controls the movement of the eyes in the vertical direction. We showed that the number of axodendritic synapses and some other morphological parameters of motoneurons changed by microgravity can return to their original state in 7 days. However, according to some parameters, motoneurons retain a “memory” of the action of microgravity and do not completely restore the structure. The volume of the soma, the shape of the nuclei, the number and orientation of dendrites do not return to pre-flight parameters. The number of dendrites after 7 days of adaptation remained increased, and the proportion of dendrites in the ventrolateral direction became 2.5 times greater than in motoneurons after space flight. The increased number of mitochondria after space flight became even more significant after readaptation. Microgravity-induced plastic changes retain to some extent “memory traces” after readaptation to Earth's gravity. It can be assumed that the restoration of the function of the trochlear nuclei (overcoming nystagmus) is carried out not only by reversible restoration of the structure of neurons, but partially using those mechanisms that are formed in weightlessness.

Ultrastructural Dendritic Changes Underlying Diaschisis After Capsular Infarct

Diaschisis has been described as functional depression distant to the lesion. A variety of neuroscientific approaches have been used to investigate the mechanisms underlying diaschisis. However, few studies have examined the pathological changes in diaschisis at ultrastructural level. Here, we used a rat model of capsular infarct that consistently produces diaschisis in ipsilesional and contralesional motor and sensory cortices. To verify the occurrence of diaschisis and monitor time-dependent changes in diaschisis, we performed longitudinal 2-deoxy-2-[18F]-fluoro-d-glucose microPET (FDG-microPET) study. We also used light and electron microscopy to identify the microscopic and ultrastructural changes at the diaschisis site at 7, 14, and 21 days after capsular infarct modeling (CIM). FDG-microPET showed the occurrence of diaschisis after CIM. Light microscopic examinations revealed no significant histopathological changes at the diaschisis site except a mild degree of reactive astrogliosis. However, electron microscopy revealed swollen, hydropic degeneration of axial dendrites and axodendritic synapses, although the neuronal soma (including nuclear chromatin and cytoplasmic organelles) and myelinated axons were relatively well preserved up to 21 days after injury. Furthermore, number of axodendritic synapses was significantly decreased after CIM. These data indicate that a circumscribed subcortical white-matter lesion produces ultrastructural pathological changes related to the pathogenesis of diaschisis.

Structure of Interneuronal Contacts in the Neuropil of the Oculomotor Nuclei in Mouse Brain under Conditions of Long-Term Microgravity

Ultrastructure of the neuropil of the brain oculomotor nuclei was studied in mice after 30-day exposure to microgravity on Bion-M1 biosatellite and after 13-h exposure to Earth gravity. The number of axo-dendritic synapses in the neuropil of the oculomotor nucleus significantly decreased after the flight. Degenerated axon terminals containing conglomerates of presynaptic vesicles appeared. The number of synapses with high functional activity increased and the length of active zones of the axo-dendritic synapses significantly increased. The observed ultrastructural changes of the neuropil of the oculomotor nuclei of mice exposed to microgravity reflect the development of long-term deafferentation of the analyzed brain structures. These changes in the neuropil ultrastructure can determine the disturbances in the oculomotor system, e.g. development of atypical nystagmus under conditions of microgravity.

Synaptic Competition Sculpts the Development of GABAergic Axo-Dendritic but Not Perisomatic Synapses

The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated mice (“γ2 knockdown mice”) with an engineered allele of the GABAAR γ2 subunit gene which produced a mosaic expression of synaptic GABAARs in neighboring neurons, causing a strong imbalance in synaptic inhibition. Deletion of the γ2 subunit did not abolish synapse formation or the targeting of NL2 to distinct types of perisomatic and axo-dendritic contacts. Thus synaptic localization of NL2 does not require synaptic GABAARs. However, loss of the γ2 subunit caused a selective decrease in the number of axo-dendritic synapses on cerebellar Purkinje cells and cortical pyramidal neurons, whereas perisomatic synapses were not significantly affected. Notably, γ2-positive cells had increased axo-dendritic innervation compared with both γ2-negative and wild-type counterparts. Moreover heterologous synapses on spines, that are found after total deletion of GABAARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABAARs in regulating synapse development in distinct subcellular compartments, and support the hypothesis that the refinement of axo-dendritic synapses is regulated by activity-dependent competition between neighboring neurons.

Stereological and allometric studies on neurons and axo-dendritic synapses in the superior cervical ganglia of rats, capybaras and horses

The superior cervical ganglion (SCG) in mammals varies in structure according to developmental age, body size, gender, lateral asymmetry, the size and nuclear content of neurons and the complexity and synaptic coverage of their dendritic trees. In small and medium-sized mammals, neuron number and size increase from birth to adulthood and, in phylogenetic studies, vary with body size. However, recent studies on larger animals suggest that body weight does not, in general, accurately predict neuron number. We have applied design-based stereological tools at the light-microscopic level to assess the volumetric composition of ganglia and to estimate the numbers and sizes of neurons in SCGs from rats, capybaras and horses. Using transmission electron microscopy, we have obtained design-based estimates of the surface coverage of dendrites by postsynaptic apposition zones and model-based estimates of the numbers and sizes of synaptophysin-labelled axo-dendritic synaptic disks. Linear regression analysis of log-transformed data has been undertaken in order to establish the nature of the relationships between numbers and SCG volume (V(scg)). For SCGs (five per species), the allometric relationship for neuron number (N) is N=35,067xV (scg) (0.781) and that for synapses is N=20,095,000xV (scg) (1.328) , the former being a good predictor and the latter a poor predictor of synapse number. Our findings thus reveal the nature of SCG growth in terms of its main ingredients (neurons, neuropil, blood vessels) and show that larger mammals have SCG neurons exhibiting more complex arborizations and greater numbers of axo-dendritic synapses.

Synaptic loss following depletion of noradrenaline and/or serotonin in the rat visual cortex: a quantitative electron microscopic study

Biogenic amines have a trophic-like role for the formation and the maintenance of synapses in the CNS. We examined the changes in the number of synaptic profiles in the developing and adult rat visual cortex following selective depletion of noradrenaline and/or serotonin. By the drug-induced decreases in levels of noradrenaline or serotonin between 1 and 2 weeks after birth, the number of synaptic profiles was decreased by 29–55% compared with that of control animals. The magnitude of reduction in the number of synaptic profiles was virtually the same following simultaneous depletion of both noradrenaline and serotonin compared with the depletion of noradrenaline or serotonin alone. Later in the developmental period, the function of noradrenaline and serotonin in facilitating synapse formation and maintenance became less prominent than that in younger animals. In the control animals, the number of axosomatic synapses was the highest at around 2 weeks after birth, and decreased with development. The number of axodendritic synapses was the highest between 2 and 7 weeks after birth, and decreased to 50% at 11 weeks after birth. These data demonstrate that synapses in the rat visual cortex are overproduced during the early developmental period. We suggest that both serotonin and noradrenaline are necessary for synapse formation during the early stages of development of the rat visual cortex.

Ultrastructural characteristics and conduction velocity of olfactory receptor neuron axons in the olfactory marker protein-null mouse

Olfactory receptor neuron (ORN) axon diameters and the conduction velocity of the compound action potential along ORN axons were studied in olfactory marker protein (OMP)-null mice and genotypically matched controls. The compound action potential was distinguished from postsynaptic field potentials by its shorter latency, its persistence following application of cobalt or kynurenic acid that blocked postsynaptic responses, and its ability to follow paired-pulse stimulation at 300 Hz. Blockade of the postsynaptic field responses by kynurenic acid indicates that in the mouse, as in the rat, glutamate is the olfactory nerve transmitter. The mean conduction velocity of ORNs in wild-type control mice was 0.47±0.19 (S.E.M.) m/s ( n=5), similar to the conduction velocity reported for other mammals. The mean diameter of ORN axons in control mice was 0.202±0.005 and 0.261±0.006 μm in the OMP-null mice. This increase in fiber diameter in the OMP-nulls predicts an increase in impulse conduction velocity. However, the mean conduction velocity of OMP-null mice, 0.38±0.03 m/s ( n=6), was not significantly different from control ( P>0.1). The conduction velocity predicted by the increase in fiber diameter in OMP-null mice was within the 95% confidence interval of the measured value. Thus, OMP-null ORNs are normal with respect to the conduction velocity of their axons. The number of axodendritic synapses in the glomeruli of OMP-null mice is higher than in congenic wild-type mice.

Early ontogeny of the vagus nerve: An analysis of the medulla oblongata and cervical spinal cord of the postnatal rat

Retrograde transport of cholera toxin conjugated with horseradish peroxidase in the postnatal rat has revealed remarkable features of dendritic fields of vagal motor neurons in the medulla oblongata and cervical spinal cord during the period of early development (0–10 days). At birth, vagal motor neurons in the dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus retroambigualis, nucleus dorsomedials and the spinal nucleus of the accessory nerve are small with relatively few, unbranched processes. The span of the dendritic tree is much smaller than that found in adult animals. By the postnatal Day 2 there are marked changes in the soma as well as in the dendritic tree of these neurons. There is dispersion of the cell bodies within the neuropil as well as an expansion of the total area of the brain stem occupied by these motor neurons and their dendritic processes which show extensive growth and branching. By postnatal Day 3 the most extensive proliferation of these neurons is seen and appears to represent the peak of dendritic growth of vagal motor neurons such that the area occupied by the dendritic tree of a single neuron is three times that seen in an adult rat. This proliferation gradually decreased during the subsequent seven days of early development (i.e. Days 4–10) so that by Day 10 the dendritic span of vagal motor neurons was reduced to about twice the adult size. This growth progressively decreased from Days 10 to 30 at which time adult levels were reached. Ultrastructural examination of these horseradish peroxidase labeled dendrites showed a positive correlation between the number of dendritic processes and the number of axo-dendritic synapses. This was accompanied by an increase in the number of identifiable synaptic junctions. These morphological complexities observed during the period of early development of vagal motor neurons indicate that the vagus nerve undergoes dramatic changes during the period of early development including the establishment of numerous synaptic contacts between vagal afferents and efferents in the brainstem. A number of these changes occur in developing dendritic fields of vagal motor neurons during the first three days of neonatal life. It is reasonable to assume that developmental abnormalities during this “critical period” could produce significant functional changes in the pattern of respiration as well as in the control of airway smooth muscle.

Estrogen increases axodendritic synapses in the VMN of rats after ovariectomy

Low doses of estrogen (E) were given to ovariectomized (OVX) rats and the ventromedial hypothalamic nucleus (VMN) was examined at the ultrastructural level. Administration of 10 micrograms of E for two consecutive days resulted in an increase in the number of axodendritic synapses in the VMN in comparison to OVX rats treated with oil. The percentage of axospine and multiple synapses and the length of the postsynaptic density were unchanged by E treatment. These results provide further support for the ability of low doses of E to alter neuronal morphology.

Intrinsic synapses in the ventromedial nucleus of the hypothalamus: an ultrastructural study.

To test the ideas that neurons intrinsic to a hypothalamic region might participate in steroid hormone effects and that intrinsic synapses might have unusual morphological features, we deafferented the ventromedial nucleus of the hypothalamus (VMH) in ovariectomized female rats with a Halasz knife. Some rats were given estrogen; others were endocrine controls. The main result of this study was that a large number of synapses in VMH survived the circumscribing cut. In fact, they comprised between one-half and two-thirds the number counted in unoperated controls. These were apparently from neuron cell bodies intrinsic to the medial basal hypothalamic island. Their morphology was not clearly different from that expected from unoperated controls or from other brain regions. A significant estrogen effect, an increase in the number of axodendritic synapses per unit area as seen in animals without surgical transections, was not present in the deafferented groups. This suggests that the hormone effect is due to synapses on VMH neurons from cell groups outside the medial basal hypothalamic island. If functional effects of estrogen mediated through VMH do not rely on intrinsic neurons, they must use estrogen-concentrating neurons that project to other brain regions.

Synaptic plasticity to estrogen in the lateral septum of the adult male and female rats

There is no sex difference in the number of axodendritic synapses in the lateral septum of adult rats. However, the treatment of adult females with estradiol (E 2) for 4 weeks increases significantly the number of synapses, whereas E 2 treatment fails to increase the synaptic number in males, suggesting a possible sexually dimorphic synaptic response to estrogen.

Synaptic remodelling in arcuate nucleus after injection of estradiol valerate in adult female rats

Adult female rats were injected with a single dose (20 mg/kg) of estradiol valerate (EV). The number of synapses was evaluated in thin sections of arcuate nucleus fixed 3, 8, 16 and 32 weeks after EV treatment and compared with the values obtained in the arcuate nucleus of uninjected proestrus control rats. By 8 weeks after EV treatment a significant ( P < 0.001) decrease was found in the number of axo-somatic and axo-dentritic synapses on dendritic shafts, but not in the number of axo-dendritic synapses on dendritic spines. However, by 32 weeks postinjection, the number of axo-somatic and axo-dendritic synapses had returned to control values. This transient decrease in the number of synapses was preceded by a massive appearance of neuronal degenerative images by 3 weeks after EV injection. These results are interpreted as reflecting a process of circuitry remodelling in the arcuate nucleus after a neuronal lesion induced by estrogen.