Although the distribution of locus ceruleus terminals has been demonstrated in the fundus striati[nucleus accumbens septi] by light microscopy[Jones & Moore, 1977 ; Mason & Fibiger, 1979 ; Streit or et al., 1979 ; Groenewegen et al., 1980], the synaptic organization of its terminals was not clarified. The purpose of the present investigation was to demonstrate the direct monosynaptic connection of the locus ceruleus terminals to the neuronal elements of the fundus stirati, and to clarify the synaptic structures of its terminals by electron microscopy two days after unilateral electric coagulation of the locus ceruleus. In the ipsilateral fundus striati, many axon terminals undergone dark degeneration were observed. These degenerating terminals containing small clear vesicles have asymmetric synaptic contacts with dendritic spines. Already two days after locus ceruleus lesion, distinct features of terminal degenerations appeared in the fundus striati ; enlarged axon terminals with altered synaptic vesicles, decrease of synaptic vesicles detached from the synaptic site, multiplication of dense bodies and infiltration of floccular material. At the same time, a regressive change occurred in which astrocytic processes encircled totally degenerated synapses spiraled around the synaptic remnants. These observations indicate that monosynaptic noradrenertic afferent connections to the fungus striati are confirmed, and the locus ceruleus terminals characterized by small round vesicles might be formed asymmetrical axo-spinous synapses with spiny neurons in the fundus striati.
Animals ; Cats* ; Dendritic Spines ; Fungi ; Locus Coeruleus* ; Microscopy, Electron ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

An attempt has been made to discriminate synaptic diversity in the neostriatum of the cat with emphasis on the characteristic structures of axon terminals and postsynaptic profiles. The differentiation of the axon terminals was based on the size and shape of synaptic vesicles in the axoplasm. Three types of axon terminals could be differentiated: Type I, the terminals contained small round (45 nm in diameter) vesicles; type II, the terminals with large pleomorphic (50 nm) vesicles; and type III, the terminals contained flattened (45 x 25 nm) vesicles. The type I terminals were making asymmetrical or symmetrical synapses in contact with the somata, dendrites and dendritic spines of neurons in the neostriatum, and a few type I terminals making asymmetrical or symmetrical contact with axons were also observed. The type II and III terminals were making symmetrical contact with the somata and dendrites of neostriatal neurons. A few type II terminals formed at the node of Ranvier of myelinated nerve fibers were making symmetrical contact with large dendrites. Additionally, dendro-dendritic and serial syanpses were rarely found in the neostriatum. In the serial synapses composed of axo-dendritic and dendro-dendritic synapses, the type I terminals making asymmetrical contact and the type II making symmetrical contact were identified.
Animals ; Axons ; Cats* ; Dendrites ; Dendritic Spines ; Neostriatum* ; Nerve Fibers, Myelinated ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

OBJECTIVE: To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice. METHODS: Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons. RESULTS: RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05). CONCLUSION RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.
Animals ; Aspartic Acid/metabolism* ; Cerebral Cortex ; Dendritic Spines/metabolism* ; Mice ; Neurons/metabolism* ; Synapses ; Tryptophan/metabolism*

BACKGROUNDIt is a common phenomenon that children experience multiple general anesthesias in clinical practice, which raises the question whether repeated exposure to general anesthetics would interfere with the development of the central nervous system of children. The present study was designed to evaluate the effects of repeated treatment with ketamine or midazolam on postnatal dendrite development by examining the morphology of the dendritic spines of the pyramidal neurons in the hippocampal CA1 region in mice.

METHODSThe transgenic green fluorescent protein-M line (GFP-M) mice were used in this study. Ketamine (100 mg/kg), midazolam (50 mg/kg) or saline (10 ml/kg) was administered intraperitoneally once a day on consecutive days from postnatal day 8 (P8) to postnatal day 12 (P12). At postnatal day 13 (P13) and postnatal day 30 (P30), the density and length of the apical dendritic spines of the pyramidal neurons in the hippocampal CA1 region were examined under a confocal microscope.

RESULTSAt P13, for both the ketamine group and the midazolam group, the dendritic spines were found with a comparatively lower density and longer average length than in the control group. At P30, no significant difference in the density or average length of dendritic spines was found between the anesthetic group and control group.

CONCLUSIONSThis study indicated that repeated exposure to ketamine or midazolam in neonatal mice impaired dendritic spine maturation immediately afterwards, but this influence seemed to disappear during further postnatal development.

Animals ; Animals, Newborn ; Dendritic Spines ; drug effects ; Female ; Hippocampus ; drug effects ; Ketamine ; pharmacology ; Male ; Mice ; Microscopy, Confocal ; Midazolam ; pharmacology

To analyze the synaptic characteristics of axon terminals originated from tooth pulp in the trigeminal principal sensory nucleus, and find morphological evidence that p-endings on these terminals use GABA as neurotransmitter, labeling of tooth pulp afferents with wheat -germ agglutinin conjugated horseradish peroxidase, postembedding immunocytochemistry and morphometric analysis were performed. The results obtained were as follows. The labeled boutons contained clear and round synaptic vesicles, and the mean number of synaptic contacts was 4.21 +/- 2.58. The postsynaptic profiles were usually middle or distal dendrites and dendritic spines rather than soma or proximal dendrites. The mean number of synaptic contacts with p -endings was 2.62 +/- 2.01. The volume of labeled bouton was 4.39 +/- 3.08 micro meter 3 and highly correlated (P<.01) with surface area (r = 0.96), total apposed surface area (r = 0.84), total active zone area (r = 0.84), mitochondrial volume (r = 0.95), the number of synaptic vesicles (r = 0.92), the number of synaptic profiles (r = 0.76) and the number of synaptic p -endings (r = 0.67). The p -endings contained pleomorphic synaptic vesicles. The volume of p -ending was 0.91 +/- 0.47 micro meter 3 and highly correlated (P<.01) with surface area (r = 0.94), total apposed surface area (r = 0.76), total active zone area (r = 0.62), mitochondrial volume (r = 0.70) and the number of synaptic vesicles (r = 0.94). P -endings were GABA immunoreactive. These results suggest that tooth pulp afferent terminals in trigeminal principal sensory nucleus may be related to complex processing of sensory information and presynaptic p -endings using GABA as neurotransmitter, are important in this sensory processing. The "size principle" of Pierce and Mendel (1993) is also applicable to tooth pulp afferent terminals and presynaptic p -endings.
Carisoprodol ; Dendrites ; Dendritic Spines ; gamma-Aminobutyric Acid ; Horseradish Peroxidase ; Immunohistochemistry ; Mitochondrial Size ; Neurotransmitter Agents ; Presynaptic Terminals ; Synaptic Vesicles ; Tooth* ; Triticum

To analyze the synaptic characteristics of axon terminals originated from the tooth pulp in the trigeminal nucleus oralis, labeling of tooth pulp afferents with wheat-germ agglutinin conjugated horseradish peroxidase and morphometric analysis with electron microscopic photographs were performed. The results obtained from 23 labeled endings were as follows. All of the labeled boutons contained clear and round synaptic vesicles (dia. 45~55 nm). 3 (13.64%) out of 23 labeled endings have 20~105 dense cored vesicles and do not make synaptic contacts with p-endings. But remaining 20 labeled endings (86.36%) almost do not have dense cored vesicles and 12 of them make synaptic contacts with p-endings. The mean number of synaptic contacts was 2.61+/-2.06 and the postsynaptic profiles were usually middle or distal dendrite and dendritic spine (1.74+/-1.36) rather than soma or proximal dendrite. The mean number of synaptic contacts with pendings was 0.87+/-1.01. And the frequency of the synaptic triads were 0.39+/-0.58. The vesicle density was 993.23+/-267.41/mum(2). The volume of labeled bouton was 3.54+/-2.20 mum(3) and highly correlated (P < 0.01) with surface area (11.78+/-4.92 mum(2), r = 0.95), total apposed surface area (2.90+/-1.56 mum(2), r=0.72), total active zone area (0.61+/-0.37 mum(2), r = 0.82), mitochondrial volume (0.75+/-0.53 mum(3), r = 0.94), the number of synaptic vesicles (2621.30+/-1473.61, r= 0.91) and the number of synaptic contacts (r = 0.76). These results suggest that there are two groups of tooth pulp afferent terminals according to the presence of dense cored vesicles in the trigeminal nucleus oralis. And the sensory processing mechanism of each groups may be different. And the "size principle" of Pierce & Mendell (1993) is also applicable to these terminals.
Carisoprodol ; Dendrites ; Dendritic Spines ; Horseradish Peroxidase ; Mitochondrial Size ; Mouth* ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles ; Tooth ; Trigeminal Nuclei*

Synaptic adhesion molecules mediate synapse formation, maturation and maintenance. These proteins are localized at synaptic sites in neuronal axons and dendrites. These proteins function as a bridge of synaptic cleft via interaction with another synaptic adhesion molecules in the opposite side. They can interact with scaffold proteins via intracellular domain and recruit many synaptic proteins, signaling proteins and synaptic vesicles. Scaffold proteins function as a platform in dendritic spines or axonal terminals. Recently, many genetic studies have revealed that synaptic adhesion molecules and scaffold proteins are important in neurodevelopmental disorders, psychotic disorders, mood disorders and anxiety disorders. In this review, fundamental mechanisms of synapse formation and maturation related with synaptic adhesion molecules and scaffold proteins are introduced and their psychiatric implications addressed.
Anxiety Disorders ; Axons ; Child ; Autism Spectrum Disorder ; Dendrites ; Dendritic Spines ; Mood Disorders ; Neurons ; Proteins ; Psychotic Disorders ; Synapses ; Synaptic Vesicles

BACKGROUND: Adult neural stem cells have the potential for self-renewal and differentiation into multiple cell lineages via symmetric or asymmetric cell division. Preso1 is a recently identified protein involved in the formation of dendritic spines and the promotion of axonal growth in developing neurons. Preso1 can also bind to cell polarity proteins, suggesting a potential role for Preso1 in asymmetric cell division. METHODS: To investigate the distribution of Preso1, we performed immunohistochemistry with adult mouse brain slice. Also, polarized distribution of Preso1 was assessed by immunocytochemistry in cultured neural stem cells. RESULTS: Immunoreactivity for Preso1 (Preso1-IR) was strong in the rostral migratory stream and subventricular zone, where proliferating transit-amplifying cells and neuroblasts are prevalent. In cultured neural stem cells, Preso1-IR was unequally distributed in the cell cytosol. We also observed the distribution of Preso1 in the subgranular zone of the hippocampal dentate gyrus, another neurogenic region in the adult brain. Interestingly, Preso1-IR was transiently observed in the nuclei of doublecortin-expressing neuroblasts immediately after asymmetric cell division. CONCLUSION: Our study demonstrated that Preso1 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, and may play a significant role in cell differentiation via association with cell polarity machinery.
Adult* ; Animals ; Asymmetric Cell Division ; Axons ; Brain ; Cell Differentiation ; Cell Lineage ; Cell Polarity ; Cytosol ; Dendritic Spines ; Dentate Gyrus ; Humans ; Immunohistochemistry ; Mice ; Neural Stem Cells ; Neurons ; Rivers

Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca2+. The Rolling mouse Nagoya (Cacna1a(tg-rol) ) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human neurological diseases such as autosomal dominant cerebellar ataxia (SCA6), familial hemiplegic migraine and episodic ataxia type-2. Morphology of Purkinje cell (PC) dendritic spine is suggested to be regulated by signal molecules such as Ca2+ and by interactions with afferent inputs. The amplitude of excitatory postsynaptic current was decreased in parallel fiber (PF) to PC synapses, whereas apparently increased in climbing fiber (CF) to PC synapses in rolling mice Nagoya. We have studied synaptic morphology changes in cerebella of this mutant strain. We previously found altered synapses between PF varicosity and PC dendritic spines. To study dendritic spine plasticity of PC in the condition of insufficient P/Q type VDCC function, we used high voltage electron microscopy (HVEM). We measured the density and length of PC dendritic spines at tertiary braches. We observed statistically a significant decrease in spine density as well as shorter spine length in rolling mice compared to wild type mice at tertiary dendritic braches. In proximal PC dendrites, however, there were more numerous dendritic spines in rolling mice Nagoya. The differential regulation of rolling PC spines at tertiary and proximal dendrites in rolling mice Nagoya suggests that two major excitatory afferent systems may be regulated reciprocally in the cerebellum of rolling mouse Nagoya.
Animals ; Ataxia ; Calcium ; Calcium Channels ; Cerebellar Ataxia ; Cerebellum ; Dendrites ; Dendritic Spines ; Excitatory Postsynaptic Potentials ; Humans ; Mice ; Microscopy, Electron ; Migraine with Aura ; Models, Animal ; Neurons ; Plastics ; Spine ; Sprains and Strains ; Synapses

GIT1, a multifunctional signaling adaptor protein, is implicated in the development of dendritic spines and neuronal synapses. GIT1 forms a signaling complex with PIX, RAC, and PAK proteins that is known to play important roles in brain development. Here we found that Git1-knockout (Git1-/-) mice show a microcephaly-like small brain phenotype, which appears to be caused by reduced neuronal size rather than number. Git1-/- mice also show decreased dendritic spine number without morphological alterations in the hippocampus. Behaviorally, Git1-/- mice show impaired motor coordination and learning and memory. In addition, adult dGit Drosophila mutants show decreased brain size and abnormal morphology of the mushroom body. These results suggest that GIT1 is important for brain development in both rodents and flies.
Adult ; Animals ; Brain* ; Dendritic Spines ; Diptera ; Drosophila ; Hippocampus ; Humans ; Invertebrates* ; Learning ; Memory ; Mice ; Microcephaly ; Mushroom Bodies ; Neurons ; Phenotype ; Rodentia ; Synapses ; Vertebrates*