-
BioMed Research International 2017Presynaptic and postsynaptic neurotoxins are proteins which act at the presynaptic and postsynaptic membrane. Correctly predicting presynaptic and postsynaptic...
Presynaptic and postsynaptic neurotoxins are proteins which act at the presynaptic and postsynaptic membrane. Correctly predicting presynaptic and postsynaptic neurotoxins will provide important clues for drug-target discovery and drug design. In this study, we developed a theoretical method to discriminate presynaptic neurotoxins from postsynaptic neurotoxins. A strict and objective benchmark dataset was constructed to train and test our proposed model. The dipeptide composition was used to formulate neurotoxin samples. The analysis of variance (ANOVA) was proposed to find out the optimal feature set which can produce the maximum accuracy. In the jackknife cross-validation test, the overall accuracy of 94.9% was achieved. We believe that the proposed model will provide important information to study neurotoxins.
Topics: Amino Acids; Computational Biology; Humans; Models, Theoretical; Neurotoxins; Presynaptic Terminals
PubMed: 28303250
DOI: 10.1155/2017/3267325 -
Annals of the New York Academy of... Mar 2013Sensory information transmitted to the spinal cord dorsal horn is modulated by a complex network of excitatory and inhibitory interneurons. The two main inhibitory... (Review)
Review
Sensory information transmitted to the spinal cord dorsal horn is modulated by a complex network of excitatory and inhibitory interneurons. The two main inhibitory transmitters, GABA and glycine, control the flow of sensory information mainly by regulating the excitability of dorsal horn neurons. A presynaptic action of GABA has also been proposed as an important modulatory mechanism of transmitter release from sensory primary afferent terminals. By inhibiting the release of glutamate from primary afferent terminals, activation of presynaptic GABA receptors could play an important role in nociceptive and tactile sensory coding, while changes in their expression or function could be involved in pathological pain conditions, such as allodynia.
Topics: Animals; Glycine; Humans; Inhibitory Postsynaptic Potentials; Models, Biological; Neural Inhibition; Posterior Horn Cells; Presynaptic Terminals; Receptors, Presynaptic; Spinal Cord; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 23531006
DOI: 10.1111/nyas.12056 -
Alcoholism, Clinical and Experimental... Aug 2006Ethanol has actions on cerebellar Purkinje neurons that can result either in a net excitation or in inhibition of neuronal activity. The present study examines the... (Comparative Study)
Comparative Study
BACKGROUND
Ethanol has actions on cerebellar Purkinje neurons that can result either in a net excitation or in inhibition of neuronal activity. The present study examines the interplay of presynaptic and postsynaptic mechanisms to determine the net effect of ethanol on the neuronal firing rate of cerebellar Purkinje neurons.
METHODS
Whole-cell voltage-clamp recording of miniature inhibitory postsynaptic currents (mIPSCs) from Purkinje neurons in cerebellar slices was used to examine the effect of ethanol on presynapticsynaptic release of gamma-aminobutyric acid (GABA) and glutamate. Extracellular recording was used to examine the net action of both presynaptic and postsynaptic effects of ethanol on the firing rate of Purkinje neurons.
RESULTS
Under whole-cell voltage clamp, the frequency of bicuculline-sensitive miniature postsynaptic currents (mIPSCs) was increased dose-dependently by 25, 50, and 100 mM ethanol without any change in amplitude or decay time. Despite this evidence of increased release of GABA by ethanol, application of 50 mM ethanol caused an increase in firing in some neurons and a decrease in firing in others with a nonrandom distribution. When both glutamatergic and GABAergic influences were removed by simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione and picrotoxin, respectively, ethanol caused only an increase in firing rate.
CONCLUSIONS
These data are consistent with a dual action of ethanol on cerebellar Purkinje neuron activity. Specifically, ethanol acts presynaptically to increase inhibition by release of GABA, while simultaneously acting postsynaptically to increase intrinsic excitatory drive.
Topics: Action Potentials; Animals; Cerebellum; Ethanol; In Vitro Techniques; Neural Inhibition; Neurons; Presynaptic Terminals; Purkinje Cells; Rats; Rats, Sprague-Dawley
PubMed: 16899043
DOI: 10.1111/j.1530-0277.2006.00167.x -
Journal of Pharmacological Sciences Jun 2003Calcium entry into nerve termini via voltage gated calcium channels is an essential step in neurotransmission. Consequently, second messenger regulation of calcium... (Review)
Review
Calcium entry into nerve termini via voltage gated calcium channels is an essential step in neurotransmission. Consequently, second messenger regulation of calcium channel activity modulates synaptic activity. It has been suggested that calcium channels must physically couple to the release machinery, and a physical interaction between a synaptic protein interaction (synprint) site contained within mammalian presynaptic calcium channels and synaptic proteins such as syntaxin 1, SNAP-25, and synaptotagmin has been demonstrated. Interestingly, synaptic calcium channels in invertebrates lack this region. In invertebrates, synaptic transmission is instead dependent on a presynaptic calcium channel splice variant that can physically associate with the adaptor proteins Mint-1 and CASK. We suggest that in the absence of a synprint region, these proteins may localize calcium channels to the synaptic release machinery. The interactions between synaptic proteins and mammalian N-type calcium channels serves to regulate calcium channel activity directly, as well as indirectly by altering second messenger regulation of the channels. This provides for a feedback mechanism that allows the fine-tuning of calcium channel activity during various steps in neurotransmitter release. This does not occur with invertebrate synaptic calcium channel homologs, suggesting that the regulation of calcium channel activity by synaptic proteins is a mechanism unique to vertebrates.
Topics: Animals; Calcium Channels; Humans; Membrane Proteins; Nerve Tissue Proteins; Presynaptic Terminals; Synaptosomal-Associated Protein 25
PubMed: 12832834
DOI: 10.1254/jphs.92.79 -
Behavioural Brain Research Aug 2011Acetylcholine release links the activity of presynaptic neurons with their postsynaptic targets and thus represents the intercellular correlate of cholinergic... (Review)
Review
Acetylcholine release links the activity of presynaptic neurons with their postsynaptic targets and thus represents the intercellular correlate of cholinergic neurotransmission. Here, we review the regulation and functional significance of acetylcholine release in the mammalian cerebral cortex, with a particular emphasis on information derived from in vivo microdialysis studies over the past three decades. This information is integrated with anatomical and behavioral data to derive conclusions regarding the role of cortical cholinergic transmission in normal behavioral and how its dysregulation may contribute to cognitive correlates of several neuropsychiatric conditions. Some unresolved issues regarding the regulation and significance of cortical acetylcholine release and the promise of new methodology for advancing our knowledge in this area are also briefly discussed.
Topics: Acetylcholine; Aging; Animals; Central Nervous System Stimulants; Cerebral Cortex; Cholinergic Fibers; Cognition; Humans; Mental Disorders; Microdialysis; Models, Neurological; Neural Pathways; Presynaptic Terminals; Prosencephalon; Synaptic Transmission
PubMed: 20170686
DOI: 10.1016/j.bbr.2010.02.022 -
Current Opinion in Neurobiology Oct 2009Axon guidance and synapse formation are important developmental events for establishing a functional neuronal circuitry. These two related cellular processes occur in a... (Review)
Review
Axon guidance and synapse formation are important developmental events for establishing a functional neuronal circuitry. These two related cellular processes occur in a coordinated fashion but previous studies from multiple model organisms seemed to suggest that axon guidance and synapse formation are mediated by distinct molecular cues. Thus, axon guidance molecules are responsible for guiding the navigating axon toward its target area, while other adhesion or ligand-receptor molecules specify the synapse formation within the target area. However, accumulative evidence has shown that axon guidance molecules can regulate the localization and formation of pre-synaptic and post-synaptic components during synapse formation. These results demonstrate a role for axon guidance molecules in synapse formation and provide insight into how axon guidance and synapse formation are coordinated at the molecular level.
Topics: Animals; Axons; Cell Movement; Models, Neurological; Presynaptic Terminals; Signal Transduction; Synapses
PubMed: 19828311
DOI: 10.1016/j.conb.2009.09.005 -
Biomolecules Apr 2020During neural development, growth cones, very motile compartments of tips of axons, lead axonal extension to the correct targets. Subsequently, presynapses, another... (Review)
Review
During neural development, growth cones, very motile compartments of tips of axons, lead axonal extension to the correct targets. Subsequently, presynapses, another axonal compartment with vigorous trafficking of synaptic vesicles, emerge to form functional synapses with postsynapses. In response to extracellular stimuli, the immediate supply of proteins by local translation within these two axonal compartments far from cell bodies confers high motility of growth cones and active vesicle trafficking in presynapses. Although local translation in growth cones and presynapses occurs at a very low level compared with cell bodies and even dendrites, recent progress in omics and visualization techniques with subcellular fractionation of these compartments has revealed the actual situation of local translation within these two axonal compartments. Here, the increasing evidence for local protein synthesis in growth cones and presynapses for axonal and synaptic functions has been reviewed. Furthermore, the mechanisms regulating local translation in these two compartments and pathophysiological conditions caused by dysregulated local translation are highlighted.
Topics: Animals; Growth Cones; Humans; Presynaptic Terminals; Protein Biosynthesis; Ribonucleoproteins
PubMed: 32344905
DOI: 10.3390/biom10050668 -
Journal of Alzheimer's Disease : JAD 2020Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially)...
BACKGROUND
Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation.
OBJECTIVE
In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans.
METHODS
We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels.
RESULTS
Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer's disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels.
CONCLUSION
In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.
Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Frontal Lobe; Humans; Male; Membrane Proteins; Presynaptic Terminals; Single-Blind Method; Surveys and Questionnaires; gamma-Tocopherol
PubMed: 32741813
DOI: 10.3233/JAD-200166 -
Journal of Neurochemistry Nov 2009Central nerve terminals release neurotransmitter in response to a wide variety of stimuli. Because maintenance of neurotransmitter release is dependent on the continual... (Review)
Review
Central nerve terminals release neurotransmitter in response to a wide variety of stimuli. Because maintenance of neurotransmitter release is dependent on the continual supply of synaptic vesicles (SVs), nerve terminals possess an array of endocytosis modes to retrieve and recycle SV membrane and proteins. During mild stimulation conditions, single SV retrieval modes such as clathrin-mediated endocytosis predominate. However, during increased neuronal activity, additional SV retrieval capacity is required, which is provided by activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mechanism during elevated neuronal activity. It is a high capacity SV retrieval mode that is immediately triggered during such stimulation conditions. This review will summarize the current knowledge regarding the molecular mechanism of ADBE, including molecules required for its triggering and subsequent steps, including SV budding from bulk endosomes. The molecular relationship between ADBE and the SV reserve pool will also be discussed. It is becoming clear that an understanding of the molecular physiology of ADBE will be of critical importance in attempts to modulate both normal and abnormal synaptic function during intense neuronal activity.
Topics: Actins; Animals; Calcineurin; Dynamin I; Endocytosis; Lipid Metabolism; Nerve Tissue Proteins; Neurons; Presynaptic Terminals; Synaptic Vesicles
PubMed: 19765184
DOI: 10.1111/j.1471-4159.2009.06384.x -
ENeuro 2018Grid cells in layer II of the medial entorhinal cortex (MEC LII) generate multiple regular firing fields in response to the position and speed of an individual within...
Grid cells in layer II of the medial entorhinal cortex (MEC LII) generate multiple regular firing fields in response to the position and speed of an individual within the environment. They exhibit a protracted postnatal development and, in the adult, show activity differences along the dorsoventral axis (DVA). Evidence suggests parvalbumin-positive (PV) interneurons, most of which are perisomatic-targeting cells, play a crucial role in generation of the hexagonal grid cell activity pattern. We therefore hypothesized that the development and organization of PV perisomatic terminals in MEC LII reflect the postnatal emergence of the hexagonal firing pattern and dorsoventral differences seen in grid cell activity. We used immuno-electron microscopy to examine the development of PV perisomatic terminals and their target somata within dorsal and ventral MEC LII in rats of postnatal day (P)10, P15, and P30. We demonstrate that in dorsal and ventral MEC LII, the cross-sectional area of somata and number and density of perisomatic PV terminals increase between P10 and P15. A simultaneous decrease was observed in cross-sectional area of PV terminals. Between P15 and P30, both MEC regions showed an increase in PV terminal size and percentage of PV terminals containing mitochondria, which may enable grid cell activity to emerge and stabilize. We also report that dorsal somata are larger and apposed by more PV terminals than ventral somata at all stages, suggesting a protracted maturation in the ventral portion and a possible gradient in soma size and PV basket innervation along the DVA in the adult.
Topics: Animals; Cell Count; Entorhinal Cortex; Male; Parvalbumins; Presynaptic Terminals; Rats, Long-Evans
PubMed: 29951577
DOI: 10.1523/ENEURO.0438-17.2018