scholarly journals Everyone on Their Own! Individualization of Synaptic Boutons

Neuron ◽  
2020 ◽  
Vol 106 (6) ◽  
pp. 875-878
Author(s):  
Ahmed A.M. Mohamed ◽  
Silke Sachse
Keyword(s):  
Synaptic Boutons

scholarly journals Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

2017 ◽  
Vol 114 (9) ◽  
pp. 2395-2400 ◽  
Author(s):  
Umesh Vivekananda ◽  
Pavel Novak ◽  
Oscar D. Bello ◽  
Yuri E. Korchev ◽  
Shyam S. Krishnakumar ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Calcium Influx ◽  
Digital Transmission ◽  
Ion Conductance ◽  
Scanning Ion Conductance Microscopy ◽  
Spike Shape ◽  
Presynaptic Spike ◽  
Synaptic Boutons ◽  
Episodic Ataxia Type

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.

scholarly journals Activity-Dependent Modulation of Neurotransmitter Innervation to Vasopressin Neurons of the Supraoptic Nucleus

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 348-354 ◽  
Author(s):  
Nancy K. Mueller ◽  
Shi Di ◽  
Charles M. Paden ◽  
James P. Herman
Keyword(s):  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Supraoptic Nucleus ◽  
Glutamate Transporter ◽  
Acid Decarboxylase ◽  
Vesicular Glutamate Transporter ◽  
Salt Loading ◽  
Synaptic Boutons ◽  
Vasopressin Neurons ◽  
Activity Dependent

Confocal microscopy was used to assess activity-dependent neuroplasticity in neurotransmitter innervation of vasopressin immunoreactive magnocellular neurons in the supraoptic nucleus (SON). Vesicular glutamate transporter 2, glutamic acid decarboxylase, and dopamine β-hydroxylase (DBH) synaptic boutons were visualized in apposition to vasopressin neurons in the SON. A decrease in DBH synaptic boutons per cell was seen upon salt loading, indicating diminished noradrenergic/adrenergic innervation. Loss of DBH appositions to vasopressin neurons was associated with a general loss of DBH immunoreactivity in the SON. In contrast, the number of vesicular glutamate transporter 2 synaptic boutons per neuron increased with salt loading, consistent with increased glutamatergic drive of magnocellular SON neurons. Salt loading also caused an increase in the total number of glutamic acid decarboxylase synaptic boutons on vasopressinergic neurons, suggesting enhanced inhibitory innervation as well. These studies indicate that synaptic plasticity compensates for increased secretory demand and may indeed underlie increased secretion, perhaps via neurotransmitter-specific, activity-related changes in synaptic contacts on vasopressinergic magnocellular neurons in the SON.

Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog

1971 ◽  
Vol 177 (1049) ◽  
pp. 509-539 ◽  
Keyword(s):  
Synaptic Transmission ◽  
Ganglion Cells ◽  
Postsynaptic Membrane ◽  
Equilibrium Potential ◽  
Neuronal Membrane ◽  
Excitatory Postsynaptic Potential ◽  
Parasympathetic Nerve ◽  
Iontophoretic Application ◽  
Synaptic Boutons ◽  
Synaptic Transmitter

Synaptic transmission has been analysed in parasympathetic nerve cells that lie in the transparent interatrial septum of the heart of the frog. Using Nomarski interference optics, one can see much cellular detail, including synaptic boutons in living preparations. 1. On each ganglion cell, the 10 to 20 synaptic boutons are usually derived from a single vagal nerve fibre. These fibres branch extensively to innervate a number of septal ganglion cells. 2. The chemical transmitter, acetylcholine (ACh), liberated by a presynaptic impulse survives for up to 40 ms, setting up an excitatory postsynaptic potential (e.p.s.p.) which triggers one and sometimes two action potentials in the postsynaptic cell. The e.p.s.p. is made up of quantal components, as at the neuromuscular junction. 3. Nerve-evoked e.p.s.p.s can be well matched in amplitude and time course by iontophoretic application of ACh to selected areas of the neuronal membrane. In particular, the miniature e.p.s.p., which is due to the focal release of a small quantity of transmitter, was accurately mimicked by iontophoretic application of ACh. By grading the amount of ACh released from an electrode one could also duplicate the wide variety of nerve-evoked postsynaptic discharges of ganglion cells. 4. The permeability changes initiated in the postsynaptic membrane by applied ACh and the synaptic transmitter appear identical, since the ionic fluxes for both responses have the same equilibrium potential. Also, the receptors which react with the synaptic transmitter are desensitized by applied ACh. 5. Cholinesterase inhibitors (Tensilon and Eserine) have a variable action on different cells, with respect both to nerve-evoked and Ach evoked potentials. The reasons for this variation are unclear, and need further study. 6. Miniature e.p.s.p.s resemble analogous potentials at nerve-muscle junctions and other synapses. A significant proportion of the min e.p.s.p.s is released as multiple units. This proportion is increased in high Ca2+, while single units alone occur in a low Ca2+-high Mg2+ environment. 7. The experiments provide information about the release of ACh from nerve terminals and its action on the postsynaptic membrane of neurons. They are in good agreement with analogous studies on skeletal neuromuscular junctions

scholarly journals DrosophilaTorsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Phuong Nguyen ◽  
Jong Bok Seo ◽  
Hyo-Min Ahn ◽  
Young Ho Koh
Keyword(s):  
Mental Retardation ◽  
Protein Complexes ◽  
Fragile X ◽  
Stress Sensitivity ◽  
Altered Expression ◽  
Fragile X Mental Retardation ◽  
Evolutionarily Conserved ◽  
Mental Retardation Protein ◽  
Synaptic Boutons

We investigated unknownin vivofunctions of Torsin by usingDrosophilaas a model. Downregulation ofDrosophilaTorsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported inDrosophilaFragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies ofdfmrpnull mutants anddfmrpmutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.

Ultrastructural Analysis of Ectopic Synaptic Boutons Arising From Peripherally Regenerated Primary Afferent Fibers

1999 ◽  
Vol 81 (4) ◽  
pp. 1636-1644 ◽  
Author(s):  
H. Richard Koerber ◽  
Karoly Mirnics ◽  
Anahid M. Kavookjian ◽  
Alan R. Light
Keyword(s):  
Dorsal Horn ◽  
Sensory Neurons ◽  
Ultrastructural Analysis ◽  
Peripheral Stimulus ◽  
Primary Sensory Neurons ◽  
Superficial Dorsal Horn ◽  
Primary Afferent ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Synaptic Boutons

Ultrastructural analysis of ectopic synaptic boutons arising from peripherally regenerated primary afferent fibers. The central axons of peripherally regenerated Aβ primary sensory neurons were impaled in the dorsal columns of α-chloralose-anesthetized cats 9–12 mo after axotomy. The adequate peripheral stimulus was determined, and the afferent fibers intracellularly stimulated while simultaneously recording the resulting cord dorsum potentials (CDPs). Fibers that successfully had reinnervated the skin responded to light tactile stimulation, and evoked CDPs that suggested dorsally located boutons were stained intracellularly with horseradish peroxidase (HRP). Two HRP-stained regenerated Aβ afferent fibers were recovered that supported large numbers of axon collaterals and swellings in laminae I, IIo, and IIi. Sections containing the ectopic collateral fibers and terminals in the superficial dorsal horn were embedded in plastic. Analyses of serial ultrathin sections revealed that ectopic projections from both regenerated fibers supported numerous synaptic boutons filled with clear round vesicles, a few large dense core vesicles (LDCVs) and several mitochondria (>3). All profiles examined in serial sections (19) formed one to three asymmetric axo-dendritic contacts. Unmyelinated portions of ectopic fibers giving rise to en passant and terminal boutons often contained numerous clear round vesicles. Several boutons (47%) received asymmetric contacts from axon terminals containing pleomorphic vesicles. These results strongly suggest that regenerated Aβ fibers activated by light tactile stimuli support functional connections in the superficial dorsal horn that have distinct ultrastructural features. In addition, the appearance of LDCVs suggests that primary sensory neurons are capable of changing their neurochemical phenotype.

scholarly journals Proteolytic maturation of α2δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ivan Kadurin ◽  
Laurent Ferron ◽  
Simon W Rothwell ◽  
James O Meyer ◽  
Leon R Douglas ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Proteolytic Cleavage ◽  
Proteolytic Processing ◽  
Calcium Currents ◽  
Cleavage Sites ◽  
Voltage Dependent ◽  
Neuronal Processes ◽  
Associated Proteins ◽  
Synaptic Boutons

The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes.

scholarly journals Investigations into modifications of neuromuscular physiology by axonal transport disruptions in Drosophila SOD1 mutants

2020 ◽  
Author(s):  
Tristan C. D. G. O’Harrow ◽  
Atsushi Ueda ◽  
Xiaomin Xing ◽  
Chun-Fang Wu
Keyword(s):  
Axonal Transport ◽  
Vital Staining ◽  
Neuronal Membrane ◽  
Adult Lifespan ◽  
Conserved Sequence ◽  
Excitatory Junction Potentials ◽  
Synaptic Boutons ◽  
And Function ◽  
Als Patients

AbstractCu/Zn superoxide dismutase (SOD1) is a cytoplasmic antioxidant enzyme, which, when mutant in humans, is linked to familial cases of the motor neurodegenerative disease amyotrophic lateral sclerosis (ALS). The Drosophila SOD1 gene (Sod) shares a highly conserved sequence with the human homolog, and this study includes examinations of the established hypomorphic n108 allele (Sodn108), alongside a knock-in construct of the G85R allele found in human ALS patients (SodG85R). In addition to previously documented decreased adult lifespan and attenuated motor function, we show that Sod mutant Drosophila can display significant mortality during larval and pupal development. Immunostaining of neuronal membrane at neuromuscular synapses in Sod mutant larvae revealed presynaptic terminals of abnormal morphology, with incompletely segregated and enlarged synaptic boutons along the motor terminal branches, in which vital staining indicated mitochondrial aggregation. We demonstrate strong genetic interactions between SodG85R and the axon transport-linked Pk mutants PkPk and PkSple in larval NMJ morphology and neuromuscular transmission. Intracellular recordings of larval excitatory junction potentials (EJPs) demonstrate enhanced EJP size in the double-mutant of PkPk and SodG85R. To examine synaptic terminal excitability, maintained by Ca2+ channel action and independent of Na+ channel function, we used the NaV blocker TTX, along with the KV1 blocker 4-aminopyridine (4-AP) and the commonly used broad-spectrum K+ channel blocker tetraethylammonium (TEA). We were able to induce prolonged “plateau-like” EJPs, which were further extended in Pk mutants and Pk;Sod double-mutants. These observations were corroborated with focal EJP recording from individual boutons. Altogether, this study highlights alterations in synaptic morphology and function at a developmental stage prior to neurodegeneration and death of Sod mutant organisms, along with a potential role of axonal transport in the maintenance of neuronal health.

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