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Current Opinion in Neurobiology Oct 2007There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity... (Review)
Review
There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2>9 months) and dynamic (t1/2 5-20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.
Topics: Animals; Brain; Neuronal Plasticity; Neurons; Presynaptic Terminals
PubMed: 17950593
DOI: 10.1016/j.conb.2007.09.002 -
Current Opinion in Cell Biology Apr 2006Neurotransmission requires proper organization of synaptic vesicle pools and rapid release of vesicle contents upon presynaptic depolarization. Genetic studies have... (Review)
Review
Neurotransmission requires proper organization of synaptic vesicle pools and rapid release of vesicle contents upon presynaptic depolarization. Genetic studies have begun to reveal a critical role for scaffolding proteins in such processes. Mutations in genes encoding components of the highly conserved MALS/CASK/Mint-1 complex cause presynaptic defects. In all three mutants, neurotransmitter release is reduced in a manner consistent with aberrant vesicle cycling to the readily releasable pool. Recently, liprin-alpha proteins, which define active zone size and morphology, were found to associate with MALS/CASK, suggesting that this complex links the presynaptic release machinery to the active zone, thereby regulating neurotransmitter release.
Topics: Adaptor Proteins, Signal Transducing; Animals; Calcium-Calmodulin-Dependent Protein Kinases; Guanylate Kinases; Humans; Membrane Proteins; Models, Biological; Nerve Tissue Proteins; Presynaptic Terminals; Synaptic Transmission
PubMed: 16504495
DOI: 10.1016/j.ceb.2006.02.010 -
Current Opinion in Neurobiology Oct 2010The classical roles of α(2)δ proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane... (Review)
Review
The classical roles of α(2)δ proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane topology, but we find that they can form GPI-anchored proteins. Moreover α(2)δ-1 and α(2)δ-3 have been shown to have novel functions in synaptogenesis, independent of their effect on calcium channels. In neurons, the α(2)δ-1 subunits are present mainly in presynaptic terminals. Peripheral sensory nerve injury results in the up-regulation of α(2)δ-1 in dorsal root ganglion (DRG) neurons, and there is a consequent increase in trafficking of α(2)δ-1 to their terminals. Furthermore, gabapentinoid drugs, which bind to α(2)δ-1 and α(2)δ-2, not only impair their trafficking, but also affect α(2)δ-1-dependent synaptogenesis. These drugs may interfere with α(2)δ function at several different levels.
Topics: Amino Acid Sequence; Animals; Calcium Channels; Ganglia, Spinal; Humans; Molecular Sequence Data; Presynaptic Terminals; Protein Transport; Sensory Receptor Cells; Synaptic Transmission; Up-Regulation
PubMed: 20579869
DOI: 10.1016/j.conb.2010.05.007 -
Journal of Cerebral Blood Flow and... Nov 2018Acute mismatch between metabolic requirements of neurons and nutrients/growth factors availability characterizes several neurological conditions such as traumatic brain...
Acute mismatch between metabolic requirements of neurons and nutrients/growth factors availability characterizes several neurological conditions such as traumatic brain injury, stroke and hypoglycemia. Although the effects of this mismatch have been investigated at cell biological level, the effects on synaptic structure and function are less clear. Since synaptic activity is the most energy-demanding neuronal function and it is directly linked to neuronal networks functionality, we have explored whether nutrient limitation (NL) affects the ultrastructure, function and composition of pre and postsynaptic terminals. We show that upon NL, presynaptic terminals show disorganized vesicle pools and reduced levels of the active zone protein Bassoon (but not of Piccolo). Moreover, NL triggers an impaired vesicle release, which is reversed by re-administration of glucose but not by the blockade of autophagic or proteasomal protein degradation. This reveals a dissociable correlation between presynaptic architecture and vesicle release, since restoring vesicle fusion does not necessarily depend from the rescue of Bassoon levels. Thus, our data show that the presynaptic compartment is highly sensitive to NL and the rescue of presynaptic function requires re-establishment of the metabolic supply rather than preventing local protein degradation.
Topics: Animals; Autophagy; Cells, Cultured; Exocytosis; Nerve Tissue Proteins; Nutrients; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Synaptic Vesicles
PubMed: 29972341
DOI: 10.1177/0271678X18786356 -
The Neuroscientist : a Review Journal... Aug 2015Synaptic vesicle (SV) retrieval from the presynaptic plasma membrane occurs via a variety of different and complementary modes. The dominant retrieval mode during... (Review)
Review
Synaptic vesicle (SV) retrieval from the presynaptic plasma membrane occurs via a variety of different and complementary modes. The dominant retrieval mode during high-intensity stimulation is activity-dependent bulk endocytosis (ADBE). ADBE involves the generation of endosomes direct from the plasma membrane which then donate membrane and cargo to form SVs that replenish the reserve SV pool. Recent evidence has suggested that ADBE may involve an additional endosomal processing step to produce a mature, functional SV. This suggests that ADBE may utilize key molecules or indeed whole pathways from classical endocytic recycling routes that are ubiquitous across all cell types. This review will assess the current evidence for a contribution of endocytic recycling to the SV life cycle, with a particular focus on ADBE. In doing so it highlights points where both routes may either converge or exploit existing mechanisms to ensure efficient generation of SVs during high-intensity stimulation.
Topics: Animals; Brain; Endocytosis; Endosomes; Humans; Presynaptic Terminals; Protein Transport; Synaptic Vesicles
PubMed: 25027635
DOI: 10.1177/1073858414542251 -
Seminars in Cell Biology Aug 1994Synaptic terminals are key elements in the functional and structural organization of the nervous system. Release of neurotransmitters, i.e. the activity specifically... (Review)
Review
Synaptic terminals are key elements in the functional and structural organization of the nervous system. Release of neurotransmitters, i.e. the activity specifically localized at the terminals, not only sustains the transfer of information among adjacent cells, but also contributes significantly to directing the non-random distribution of macromolecules in the plasmalemma of postsynaptic neurons, with major consequences in their general architecture (assembly of postsynaptic densities, dendritic spines, etc.). In order for these specific functions to be carried out, synaptic terminals need to be specialized in a variety of aspects with respect to the rest of the neuron. This minireview is specifically focused on two such aspects, the generation of transduction signals and their mechanism of action on intraterminal targets. In either aspect nerve terminals are by no means fully homogeneous, yet they certainly share a number of common features. These include the predominant role of Ca2+, collaborating however with other second messengers (cAMP, IP3, diacylglycerol) in the control of processes such as transmitter release and its modulation.
Topics: Animals; Calcium; Calcium Channels; Endocytosis; Exocytosis; Humans; Presynaptic Terminals; Receptors, Presynaptic; Second Messenger Systems; Signal Transduction
PubMed: 7994005
DOI: 10.1006/scel.1994.1027 -
Journal of Chemical Neuroanatomy Oct 2016All animals have to find the right balance between investing resources into their reproductive cycle and protecting their tissues from age-related damage. In higher... (Review)
Review
All animals have to find the right balance between investing resources into their reproductive cycle and protecting their tissues from age-related damage. In higher order organisms the brain is particularly vulnerable to ageing, as the great majority of post-mitotic neurons are there to stay for an entire life. While ageing is unavoidable, it may progress at different rates in different individuals of the same species depending on a variety of genetic and environmental factors. Inevitably though, ageing results in a cognitive and sensory-motor decline caused by changes in neuronal structure and function. Besides normal ageing, age-related pathological conditions can develop in a sizeable proportion of the population. While this wide array of diseases are considerably different compared to physiological ageing, the two processes share many similarities and are likely to interact. At the subcellular level, two key structures are involved in brain ageing: axons and their synapses. Here I highlight how the ageing process affects these structures in normal and neurodegenerative states in different brain areas.
Topics: Aging; Animals; Axons; Humans; Nervous System; Presynaptic Terminals
PubMed: 26698224
DOI: 10.1016/j.jchemneu.2015.12.005 -
Journal of Psychopharmacology (Oxford,... Jan 2021The therapeutic effects of antipsychotic drugs (APDs) are mainly attributed to their postsynaptic inhibitory functions on the dopamine D2 receptor, which, however,...
BACKGROUND
The therapeutic effects of antipsychotic drugs (APDs) are mainly attributed to their postsynaptic inhibitory functions on the dopamine D2 receptor, which, however, cannot explain the delayed onset of full therapeutic efficacy. It was previously shown that APDs accumulate in presynaptic vesicles during chronic treatment and are released like neurotransmitters in an activity-dependent manner triggering an auto-inhibitory feedback mechanism. Although closely mirroring therapeutic action onset, the functional consequence of the APD accumulation process remained unclear.
AIMS
Here we tested whether the accumulation of the APD haloperidol (HAL) is required for full therapeutic action in psychotic-like rats.
METHODS
We designed a HAL analog compound (HAL-F), which lacks the accumulation property of HAL, but retains its postsynaptic inhibitory action on dopamine D2 receptors.
RESULTS/OUTCOMES
By perfusing LysoTracker fluorophore-stained cultured hippocampal neurons, we confirmed the accumulation of HAL and the non-accumulation of HAL-F. In an amphetamine hypersensitization psychosis-like model in rats, we found that subchronic intracerebroventricularly delivered HAL (0.1 mg/kg/day), but not HAL-F (0.3-1.5 mg/kg/day), attenuates psychotic-like behavior in rats.
CONCLUSIONS/INTERPRETATION
These findings suggest the presynaptic accumulation of HAL may serve as an essential prerequisite for its full antipsychotic action and may explain the time course of APD action. Targeting accumulation properties of APDs may, thus, become a new strategy to improve APD action.
Topics: Animals; Antipsychotic Agents; Cells, Cultured; Dopamine D2 Receptor Antagonists; Drug Delivery Systems; Haloperidol; Hippocampus; Inhibitory Postsynaptic Potentials; Presynaptic Terminals; Psychotic Disorders; Rats; Receptors, Dopamine D2; Synaptic Vesicles
PubMed: 33274688
DOI: 10.1177/0269881120965908 -
Annual Review of Neuroscience 2001alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is a large... (Review)
Review
alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell-surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion. Binding of alpha-latrotoxin to these receptors does not in itself trigger exocytosis but serves to recruit the toxin to the synapse. Receptor-bound alpha-latrotoxin then inserts into the presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter-specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA, acetylcholine) is induced in a calcium-independent manner by a direct intracellular action of alpha-latrotoxin, while exocytosis of catecholamines requires extracellular calcium. Elucidation of precisely how alpha-latrotoxin works is likely to provide major insight into how synaptic vesicle exocytosis is regulated, and how the release machineries of classical and catecholaminergic neurotransmitters differ.
Topics: Animals; Black Widow Spider; Humans; Nerve Tissue Proteins; Neurotransmitter Agents; Presynaptic Terminals; Receptors, Peptide; Spider Venoms; Synapses
PubMed: 11520923
DOI: 10.1146/annurev.neuro.24.1.933 -
Brain and Nerve = Shinkei Kenkyu No... Jul 2011Our higher brain functions such as learning and memory, emotion, and consciousness depend on the precise regulation of complicated neural networks in the brain. Neurons... (Review)
Review
Our higher brain functions such as learning and memory, emotion, and consciousness depend on the precise regulation of complicated neural networks in the brain. Neurons communicate with each other through the synapse, which comprise 3 regions: the presynapse, synaptic cleft, and postsynapse. The active zone (AZ) beneath the presynaptic membrane is the principal site for Ca2+ -dependent neurotransmitter release: AZ is involved in determining the site for docking and synaptic vesicle fusion. Presently, the full molecular composition of AZ is unclear, but it is known to contain several AZ-specific proteins, including cytomatrix of the active zone-associated protein (CAST)/ERC2, ELKS, RIM1, Munc13-1, Piccolo/Aczonin, and Bassoon. CAST and ELKS are novel active zone proteins that directly bind to Rab3-interacting molecules (RIMs), Bassoon, and Piccolo, and are thought to play a role in neurotransmitter release by binding these to AZ proteins. In this review, current advances in studies on AZ structure and function have been summarized, and the focus is mainly on protein-protein interactions among the AZ proteins.
Topics: Calcium Channels; Humans; Nerve Tissue Proteins; Neurotransmitter Transport Proteins; Presynaptic Terminals
PubMed: 21747133
DOI: No ID Found