Ultrastructural Changes In Synapses Research Articles

Structural aspects of the aging invertebrate brain.

Aging is characterized by a decline in neuronal function in all animal species investigated so far. Functional changes are accompanied by and may be in part caused by, structurally visible degenerative changes in neurons. In the mammalian brain, normal aging shows abnormalities in dendrites and axons, as well as ultrastructural changes in synapses, rather than global neuron loss. The analysis of the structural features of aging neurons, as well as their causal link to molecular mechanisms on the one hand, and the functional decline on the other hand is crucial in order to understand the aging process in the brain. Invertebrate model organisms like Drosophila and C. elegans offer the opportunity to apply a forward genetic approach to the analysis of aging. In the present review, we aim to summarize findings concerning abnormalities in morphology and ultrastructure in invertebrate brains during normal aging and compare them to what is known for the mammalian brain. It becomes clear that despite of their considerably shorter life span, invertebrates display several age-related changes very similar to the mammalian condition, including the retraction of dendritic and axonal branches at specific locations, changes in synaptic density and increased accumulation of presynaptic protein complexes. We anticipate that continued research efforts in invertebrate systems will significantly contribute to reveal (and possibly manipulate) the molecular/cellular pathways leading to neuronal aging in the mammalian brain.

Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies.

The correlation between dysfunction in the glutamatergic system and neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, is undisputed. Both disorders are associated with molecular and ultrastructural alterations that affect synaptic plasticity and thus the molecular and physiological basis of learning and memory. Altered synaptic plasticity, accompanied by changes in protein synthesis and trafficking of postsynaptic proteins, as well as structural modifications of excitatory synapses, are critically involved in the postnatal development of the mammalian nervous system. In this review, we summarize glutamatergic alterations and ultrastructural changes in synapses in schizophrenia and autism spectrum disorder of genetic or drug-related origin, and briefly comment on the possible reversibility of these neuropsychiatric disorders in the light of findings in regular synaptic physiology.

Synaptic degeneration in rat brain after prolonged oral exposure to silver nanoparticles

Neurotoxicity of silver nanoparticles has been confirmed in both in vitro and in vivo studies. However, the mechanisms of the toxic action have not been fully clarified. Since nanoparticles are likely to have the ability to enter the brain and significantly accumulate in this organ, it is important to investigate their neurotoxic mechanisms. Here we examine the effect of prolonged exposure of rats to small (10nm) citrate-stabilized silver nanoparticles (as opposed to the ionic silver) on synapse ultrastructure and specific proteins. Administration of both nanosilver and ionic silver over a two-week period resulted in ultrastructural changes including blurred synapse structure and strongly enhanced density of synaptic vesicles clustering in the center of the presynaptic part. Disturbed synaptic membrane leading to liberation of synaptic vesicles into neuropil, which testifies for strong synaptic degeneration, was characteristic feature observed under AgNPs exposure. Also a noteworthy finding was the presence of myelin-like structures derived from fragmented membranes and organelles which are associated with neurodegenerative processes. Additionally, we observed significantly decreased levels of the presynaptic proteins synapsin I and synaptophysin, as well as PSD-95 protein which is an indicator of postsynaptic densities. The present study demonstrates that exposure of adult rats to both forms of silver leads to ultrastructural changes in synapses. However, it seems that small AgNPs lead to more severe synaptic degeneration, mainly in the hippocampal region of brain. The observations may indicate impairment of nerve function and, in the case of hippocampus, may predict impairment of cognitive processes.

Distinct roles of dopamine D3 receptors in modulating methamphetamine‐induced behavioral sensitization and ultrastructural plasticity in the shell of the nucleus accumbens

Persistent changes in behavior and psychological function that occur as a consequence of exposure to drugs of abuse are thought to be mediated by the structural plasticity of specific neural circuits such as the brain's dopamine (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc) accompany drug-induced enduring behavioral and molecular changes, yet ultrastructural changes in synapses following repeated exposure to drugs have not been well studied. The current study examines the role of DA D3 receptors in modulating locomotor activity induced by both acute and repeated methamphetamine (METH) administration and accompanying ultrastructural plasticity in the shell of NAc in mice. We found that D3 receptor mutant (D3−/−) mice exhibited attenuated acute locomotor responses as well as the development of behavioral sensitization to METH compared with wild-type mice. In the absence of obvious neurotoxic effects, METH induced similar increases in synaptic density in the shell of NAc in both wild-type and D3−/− mice. These results suggest that D3 receptors modulate locomotor responses to both acute and repeated METH treatment. In contrast, the D3 receptor is not obviously involved in modulating baseline or METH-induced ultrastructural changes in the NAc shell.

The effects of chronic haloperidol administration on GABA‐immunoreactive. Axon terminals in rat medial prefrontal cortex

Several reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma-aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA-immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA-containing terminals were visualized with an avidin-biotin immunoperoxidase method for localizing anti-GABA antibodies. Computer-assisted image processing was employed to determine the total number of pixels representing GABA-immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug-treated animals showed a significant increase in the number of pixels representing GABA-immunoreaction product in axosomatic terminals of layers II, III, VI, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA-containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non-dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5-HT2 or sigma opiate receptors play a role.

Ultrastructural changes in synapses of cortical neurons following combined applications of glutamate and noradrenaline

The dimensions of postsynaptic densities (PSD) of axodendritic synapses in the sensorimotor region of the rat neocortex were determined following multiple paired microiontophoretic applications of L-glutamate (Gl) and noradrenaline (NA) using electron microscopy. It was established that combined applications of Gl and NA induce a statistically significant increase in the thickness of the PSD. In this case, the intensity of the structural changes depends on the delay time (within the range of 0–5 sec) of NA action in relation to Gl. The strongest modification in PSD was observed whenever the second neurochemical signal was received at the amount of cessation of the neuronal response to the action of the first transmitter.

Ultrastructural changes in synapses of rat cortical neurons on their functional isolation by means of EGTA ionophoresis

Ultrastructural changes in synapses of rat cortical neurons on their functional isolation by means of EGTA ionophoresis

Quantitative analysis of ultrastructural changes in synapses of the rat hippocampal field CA3 in vitro in different functional states

Transverse slices (250–350 μm) of the rat hippocampus were used for estimation of quantitative correlations between the ultrastructure and function of giant spinous synapses localized in stratum lucidum of the field CA3. Spontaneous and evoked spike discharges were used to determine the following five functional states of the neurons: (1) “control”; (2) “depletion” was achieved by long-term continuous stimulation (30–50 Hz for 1 h and longer); (3) “recovery” when the slices rested after “depletion” till the evoked response was recovered; (4) long-term potentiation I was achieved by short-term tetanic stimulation (5–15 s, 50–70 Hz); (5) long-term potentiation II was achieved by a similar tetanic stimulation as for long-term potentiation I after the “recovery”. For quantitative analysis of ultrastructural changes in the giant spinous synapses the following parameters were used: density of presynaptic vesicles determined as a ratio between the number of vesicles located within the giant bouton and the area of the latter (number of vesicles per 1 μm 2); vesicle diameter distribution; area and length of the postsynaptic densities. A correlation of these parameters with the functional state of CA3 neurons was found. The area and length of postsynaptic densities are the most statistically significant parameters of the giant spinous synapses in different functional states. In contrast to other states, an increase in the length and the area of postsynaptic densities in long-term potentiation was found. A hypothesis on postsynaptic densities' role in long-term potentiation formation is suggested. The role of presynaptic and postsynaptic ultrastructural rearrangements is discussed as a possible mechanism determining the efficiency of synaptic transmission.

Morphological and functional changes in sensomotor cortical synapses during the summation reflex in rabbits.

1. Electron-microscopic study of synapses in the rabbit sensomotor cortex during the summation reflex reveals structural changes in the pre- and postsynaptic components of axodendritic synapses, possibly as a result of increased functional activity of the synaptic apparatus. 2. The strongest response to a combination of stimuli is observed in the postsynaptic matrix, and it results in marked thickening of the postsynaptic membranes in some axo-dendritic synapses. 3. The character of ultrastructural changes in synapses in the sensomotor cortex during formation of simple forms of temporary connection makes it appear likely that the postsynaptic membrane of axo-dendritic synapses is one of the earliest sites of structural consolidation of traces of incoming information.

Ultrastructural changes in synapses of the rabbit sensomotor cortex during stimulation of the reticular formation

Ultrastructural changes were studied in synapses of the sensomotor cortex of rabbits during short-term (25 stimuli during 1 day) and long-term stimulation of RF (400 stimuli in the course of 7–8 days). 1. Short-term stimulation of RF led to the development and increased complexity of structures of the synapses, in the form of the appearance of numerous axon terminals forming several active zones with the postsynaptic neuron, and to an increase in the number of synaptic vesicles in the axon terminals. 2. During long-term stimulation of RF further transformations took place in the synapses, namely an increase in the area of the active zones and a decrease in the number of synaptic vesicles in the axon terminals. 3. The submicroscopic changes observed in the synaptic apparatus during stimulation of RF are regarded as a process of intensification of the functional activity of the synaptic apparatus of the sensomotor cortex with the bringing of new interneuronal connections into operation. 4. Structural and functional transformations in the synaptic apparatus of rabbits take place throughout the cross-section of the sensomotor cortex, but predominantly at the upper level (layers I–IV), which suggests that nonspecific afferent endings are distributed throughout all layers of the sensomotor cortex but are represented chiefly in the upper layers.

Ultrastructural changes in synapses in the dentate gyrus of the rat during development

The structural transformations in synapses and dendrites in the molecular layer of the dentate gyrus of the rat are described. The appearance of the molecular layer of an adult is distinguished by the presence of numerous complex spines which in thin sections form a ‘U’- or ‘W’-shaped contact with a presynaptic terminal or bouton en passage. The great majority of synaptic connections in the adult are made with spines, and most synaptic contacts on spines are of an asymmetric type. In the molecular layer of the 4-day-old rat complex spines are rare and synapses sparse. Synaptic contacts exist on large or small dendritic shafts and are often of teh symmetric type. Complex spines appear to develop at locations closest to the granule cell body and gradually come to occupy the entire dendritic field. At 25 days complex spines become prominent, and by adulthood complex spines and the spine apparatus are more abundant than at earlier stages examined. Thus, in contrast to synaptogenesis, whicb is essentially complete by 25 days, complex spine formation is more prolonged.