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PubMed1998

A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant synapse.

Sec1-related proteins are essential for membrane fusion at distinct stages of the constitutive and regulated secretory pathways in eukaryotic cells. Studies of neuronal isoforms of the Sec1 protein family have yielded evidence for both positive and negative regulatory functions of these proteins in neurotransmitter release. Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and examined its function in neurotransmitter release at the squid giant synapse. Microinjection of s-Sec1 into the presynaptic terminal of the giant synapse inhibited evoked neurotransmitter release, but this effect was prevented by coinjecting the cytoplasmic domain of squid syntaxin (s-syntaxin), one of the binding partners of s-Sec1. A 24 amino acid peptide fragment of s-Sec1, which inhibited the binding of s-Sec1 to s-syntaxin in vitro, completely blocked release, suggesting an essential function of the s-Sec1/s-syntaxin interaction in transmitter release. Electron microscopy showed that injection of s-Sec1 did not change the spatial distribution of synaptic vesicles at presynaptic release sites ("active zones"), whereas the inhibitory peptide increased the number of docked vesicles. These distinct morphological effects lead us to conclude that Sec1 proteins function at different stages of synaptic vesicle exocytosis, and that an interaction of s-Sec1 with syntaxin-at a stage blocked by the peptide-is necessary for docked vesicles to fuse.

Animals↗
PubMed1997

PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease.

PET and: markers for the pre- and postsynaptic neurons were used to study the dopamine system in vivo in Huntington's disease. The radioligands used were [11C]SCH 23390 for D1-receptors, [11C]raclopride for D2-receptors and [11C]beta-CIT for dopamine transporters. Five patients with Huntington's disease and five matched controls were recruited. Brain anatomy was examined by MRI. The findings in patients were as follows. Postsynaptic D1- and D2-receptor densities were similarly reduced in the striatum. A reduction in D1-receptor density was shown in the temporal cortex; it draws attention to the cortical degeneration in relation to the cognitive deficits observed in Huntington's disease. The reduction of D1- and D2-receptor binding potentials in the striatum correlated significantly with increasing duration of illness. The correlation between the duration of illness and decline of D1- and D2-receptors make these receptors valuable as quantitative markers for the Huntington's disease degenerative process. Besides postsynaptic changes, a significant 50% decrease of [11C]beta-CIT binding to the dopamine transporter was found in the striatum. A reduced striatal blood flow in Huntington's disease cannot be excluded and could account for a small part of the decrease in [11C]beta-CIT binding. We suggest that the finding reflects a loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease.

Adult↗
PubMed1990

[Changes in the processes of vesicular recycling in the hippocampal presynapses during the modelling of glutamate neurotoxicity].

In order to test directly morphofunctional changes in presynaptic terminals (PTs) of hippocampal slice preparations (28 day-old rats, Ca 1 neurons), their ultrastructure was studied electron-microscopically under 0.5 h exposure of 500 mumol/l. glutamate added into the incubation medium. The morphometrical and statistical stereological approach has demonstrated a sufficient rise in the mean number of exo/endocytosis caveolae per a PT (up to 13), an increase of PTs surface area (from 2.23 to 3.15 microns, on the average), whereas the mean PTs volume was practically unchanged as compared to the controls. These quantitative data have allowed estimating changes in physical and chemical presynaptic membrane parameters, correlating with the observed plastic alterations under increased extracellular glutamate concentration. It has been shown that the studied effects can take place during earlier stages of the long-term potentiation development.

Animals↗
PubMed1997

Positron emission tomography studies of healthy volunteers--no effects on the dopamine terminals and synthesis after short-term exposure to toluene.

Despite extensive research, the mechanisms for the effects of organic solvents on the central nervous system are still unknown. One mechanism proposed is that solvents interfere with the synthesis of neurotransmitters. In the present study 11 male healthy volunteers were exposed during 15 min to 100 p.p.m. toluene at light physical exercise, and the dopamine decarboxylase activity and number of terminals in putamen were measured before and after exposure by positron emission tomography. Two different tracers were used [beta-11C]L-DOPA for decarboxylase activity during the in vivo synthesis of dopamine, and [11C]nomifensine to estimate the number of terminals. Although there was a slight increase in the rate of dopamine synthesis in the putamen after the exposure, this difference was not statistically significant (P = 0.4). No effect was observed with regard to the uptake of nomifensine. There was no significant relationship between the dose of toluene and rate of dopamine synthesis, and no significant correlation between the time from end of exposure to start of the PET-camera and DOPA. Our findings indicate that short term exposure to 100 p.p.m. of toluene does not affect the rate of dopamine synthesis or the number of presynaptic terminals.

Adult↗
PubMed2006

Activity-independent prespecification of synaptic partners in the visual map of Drosophila.

Specifying synaptic partners and regulating synaptic numbers are at least partly activity-dependent processes during visual map formation in all systems investigated to date . In Drosophila, six photoreceptors that view the same point in visual space have to be sorted into synaptic modules called cartridges in order to form a visuotopically correct map . Synapse numbers per photoreceptor terminal and cartridge are both precisely regulated . However, it is unknown whether an activity-dependent mechanism or a genetically encoded developmental program regulates synapse numbers. We performed a large-scale quantitative ultrastructural analysis of photoreceptor synapses in mutants affecting the generation of electrical potentials (norpA, trp;trpl), neurotransmitter release (hdc, syt), vesicle endocytosis (synj), the trafficking of specific guidance molecules during photoreceptor targeting (sec15), a specific guidance receptor required for visual map formation (Dlar), and 57 other novel synaptic mutants affecting 43 genes. Remarkably, in all these mutants, individual photoreceptors form the correct number of synapses per presynaptic terminal independently of cartridge composition. Hence, our data show that each photoreceptor forms a precise and constant number of afferent synapses independently of neuronal activity and partner accuracy. Our data suggest cell-autonomous control of synapse numbers as part of a developmental program of activity-independent steps that lead to a "hard-wired" visual map in the fly brain.

Animals↗
PubMed2000

Long-term potentiation of primary afferent neurotransmission at trigeminal synapses of juvenile rats.

Primary afferent monosynaptic and polysynaptic excitatory postsynaptic currents (EPSCs) were recorded from brainstem trigeminal neurons by stimulation of the mandibular nerve attached to the brainstem preparation of juvenile rats. A high-frequency conditioning stimulus induced long-term potentiation (LTP) of high-threshold EPSCs in the majority of trigeminal caudal neurons in substantia gelatinosa, where both A- and C-fibres terminate. However, the same conditioning stimulus did not potentiate low-threshold EPSCs in caudal neurons or EPSCs recorded from neurons in the middle part of trigeminal interpolar nucleus, where C-fibres rarely terminate. LTP in caudal neurons could be induced after blocking N-methyl-D-aspartate (NMDA) receptors with D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 microM), after postsynaptic loading of the Ca2+ chelator BAPTA (10 mM), or even after completely blocking excitatory transmission with kynurenic acid during conditioning. However, LTP was blocked by the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (1 mM). We suggest that LTP of the trigeminal primary afferent EPSCs is induced preferentially in the C-fibre inputs and that the induction mechanism involves metabotropic glutamate receptors, possibly at the presynaptic terminals.

2-Amino-5-phosphonovalerate↗
PubMed1999

Synucleins in synaptic plasticity and neurodegenerative disorders.

Synucleins are small highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched at presynaptic terminals. Three genes in humans produce closely related synuclein proteins, all of which share a large amphipathic domain capable of reversible binding to lipid vesicles. Alpha synuclein has been specifically implicated in neurodegenerative disease. Two point mutations are genetically linked to familial Parkinson's disease, and alpha synuclein appears to form the major fibrillary component of Lewy bodies. Alpha synuclein also contributes to the intracellular inclusions of multiple system atrophy, and a fragment has been found in senile plaques in Alzheimer's disease. Although their normal cellular functions are unknown, several observations suggest the synucleins may serve to integrate presynaptic signaling and membrane trafficking. Alpha synuclein has been identified as a potent and selective inhibitor of phospholipase D2, which produces phosphatidic acid (to which synuclein binds) and is believed to function in the partitioning of membranes between the cell surface and intracellular stores. We outline a hypothesis whereby synuclein supports localized, experience-dependent turnover of synaptic membranes. Such a process may be important for lifelong learning and memory functions and may be especially vulnerable to disruption in aging-associated neurodegenerative diseases.

Animals↗
PubMed1988

Immunoglobulins from amyotrophic lateral sclerosis patients enhance spontaneous transmitter release from motor-nerve terminals.

Amyotrophic lateral sclerosis (ALS) is an incapacitating neuromuscular disease of unknown etiology. Although laboratory evidence is lacking, circumstantial evidence supports the importance of immune factors in the pathogenesis of ALS. In the present study immunoglobulins from 4 of 8 ALS patients induced a significant increase in spontaneous quantal transmitter release as monitored by miniature end-plate potential (MEPP) frequency in mouse phrenic nerve-diaphragm preparations at 23 degrees C, whereas immunoglobulins from normal individuals and from patients with other neuromuscular diseases had no effect. At 32 degrees C neither normal nor disease control immunoglobulins influenced MEPP frequency, but 8 of 11 ALS immunoglobulin samples produced a significant increase in spontaneous quantal transmitter release. The enhancing effect could be prevented by 10 mM Mg2+. No effects were noted on MEPP amplitude and muscle resting potential. These findings suggest that the presynaptic terminal of the motor neuron may be an early target and that immunological factors may play an important role in the disease process.

Amyotrophic Lateral Sclerosis↗
PubMed1983

Structural and functional analysis of synaptic transmission between identified leech neurones in culture.

The fine structure and physiological properties of chemical synapses that develop between identified leech neurones in culture have been studied by electron microscopy and by quantal analysis. Earlier work has shown that the transmitter liberated by isolated Retzius cells, serotonin, evokes chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s) in P sensory cells, and also in Retzius cells. When pairs of Retzius cells or Retzius and P sensory cells were placed in close apposition in culture for a few days, their somata extended numerous fine processes which came into contact and interdigitated. In the region of interdigitation, only narrow spaces, approximately 20-25 nm wide separated the membranes. The appearance of the cytoplasm of the two neurones was distinctive: in particular, Retzius cells contained agranular vesicles, as well as abundant dense core vesicles which were not as prevalent in P cells. Structures resembling synapses developed by 4 days, with characteristic vesicles clustered in terminals of the Retzius cell apposed to the post-synaptic membrane. In the presence of raised Mg or lowered Ca in the culture medium, the i.p.s.p. in the P cell evoked by an impulse in the Retzius cell became diminished in amplitude. The time-to-peak and half-time of decay were unchanged. Under these conditions, with repeated stimulation, quantal fluctuations of these post-synaptic potentials and failures were observed. In addition, there occurred spontaneous events which resembled miniature synaptic potentials and had amplitudes and time courses similar to those of the unitary events evoked by presynaptic impulses. The amplitudes of evoked synaptic potentials in raised Mg were distributed in accord with the Poisson equation. The agreement was good when either the spontaneous miniature potentials or the failures of evoked release were used to calculate m, the mean number of quanta per trial. With larger values of m the results were distributed as predicted by the binomial equation. These morphological and electrophysiological experiments together indicate that the inhibitory potentials observed in P cells result from quantal units of transmitter released by presynaptic terminals of the Retzius cell which are in close apposition to the post-synaptic membrane.

Action Potentials↗
PubMed1986

Voltage dependence of 5-hydroxytryptamine release at a synapse between identified leech neurones in culture.

The release of 5-hydroxytryptamine (5-HT) from presynaptic terminals has been studied by the voltage-clamp technique at synapses made by isolated Retzius and pressure (P) sensory neurones dissected from the leech C.N.S. and maintained in tissue culture. At these synapses facilitation, depression and modulation of release occur with action potentials and with voltage-clamp pulses. Depolarization of Retzius cells from a constant holding potential by steps of varying amplitude (5 ms in duration) caused graded release of 5-HT. The steep transfer function for release using these short test pulses resembled that seen at the giant synapse of the squid: synaptic potentials increased markedly with presynaptic depolarizations beyond -25 mV and decreased with large depolarizing pulses beyond +40 mV. When the steady holding potential of voltage-clamped Retzius cells was suddenly displaced to a new value within the range of -40 mV to -85 mV, there followed a slow but smaller change of the post-synaptic P-cell membrane potential in the same direction. After an initial delay of about 40 ms, the post-synaptic potential reached its new level with an exponential time course and a time constant of 0.7 s. Since Retzius and P cells are not electrically coupled, these effects can be accounted for by alterations in tonic release of transmitter. Changes of presynaptic holding potential to a more depolarized level resulted in an increase in voltage noise recorded in the P cell. Conversely, hyperpolarization from a depolarized level reduced noise. Noise analysis showed that these changes could be accounted for by quantal events with a mean amplitude of about 0.15 mV. This value is similar to that for spontaneous miniature potentials and quantal fluctuations observed at synapses between Retzius and P cells. Changes in steady holding potential also had marked effects upon the transfer function observed with brief depolarizing pulses of the Retzius cell. The post-synaptic responses evoked by depolarizations to 0 mV with pulses of 5 ms duration were reduced in amplitude as the holding potential of the Retzius cell was increased from the resting value of -45 to -75 mV. For example, depolarization to 0 mV starting from -45 mV evoked synaptic potentials as much as ten times larger than those evoked by depolarizations to 0 mV starting from -75 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMedDate not supplied

Microwave radiation, in the absence of hyperthermia, has no detectable effect on synapsin I levels or phosphorylation.

Recent reports have indicated that microwave radiation can produce effects on a variety of cell types in vitro. To determine whether microwave radiation might be neurotoxic, the effects of microwave radiation on synapsin I have been examined. Synapsin I is a neuron-specific phosphoprotein that is present in all neurons, where it is localized to the presynaptic terminal and is associated with synaptic vesicles. O'Callaghan and Miller have demonstrated that studies of such neuron-specific proteins can provide reliable indices of neurotoxicity. We have used a radioimmunoassay for synapsin I to determine whether microwave irradiation has any effect on the levels of synapsin I. Neither acute nor chronic exposure to microwave irradiation had any detectable effect on synapsin I levels. We have also examined the calcium-dependent phosphorylation of synapsin I in synaptosomes isolated from rats that had been subjected to microwave radiation. The phosphorylation of synapsin I in synaptosomes reflects numerous components of the presynaptic aspect of neuronal transmission. At intensities below that required to produce mild hyperthermia, no effects of microwave irradiation were seen on synapsin I phosphorylation.

Animals↗
PubMed1996

Effects of subchronic clozapine and haloperidol on striatal glutamatergic synapses.

Subchronic treatment with haloperidol increases the number of asymmetric glutamate synapses associated with a perforated postsynaptic density in the striatum. To characterize these synaptic changes further, the effects of subchronic (28 days) administration of an atypical antipsychotic, clozapine (30 mg/kg, s.c.), or a typical antipsychotic, haloperidol (0.5 mg/kg, s.c.), on the binding of [3H] MK-801 to the NMDA receptor-linked ion channel complex and on the in situ hybridization of riboprobes for NMDAR2A and 2B subunits and splice variants of the NMDAR1 subunit were examined in striatal preparations from rats. The density of striatal glutamate immunogold labeling associated with nerve terminals of all asymmetric synapses and the immunoreactivity of those asymmetric synapses associated with a perforated postsynaptic density were also examined by electron microscopy. Subchronic neuroleptic administration had no effect on [3H] MK-801 binding to striatal membrane preparations. Both drugs increased glutamate immunogold labeling in nerve terminals of all asymmetric synapses, but only haloperidol increased the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated postsynaptic density. Whereas subchronic administration of clozapine, but not haloperidol, resulted in a significant increase in the hybridization of a riboprobe that labels all splice variants of the NMDAR1 subunit, both drugs significantly decreased the abundance of NMDAR1 subunit mRNA containing a 63-base insert. Neither drug altered mRNA for the 2A subunit, but clozapine significantly increased hybridization of a probe for the 2B subunit. The data suggest that some neuroleptic effects may be mediated by glutamatergic systems and that typical and atypical antipsychotics can have varying effects on the density of glutamate in presynaptic terminals and on the expression of specific NMDA receptor splice variant mRNAs. Alternatively, NMDAR1 subunit splice variants may differentially respond to interactions with glutamate.

Alternative Splicing↗
PubMed2005

Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass spectrometry.

Synaptosomes are isolated synapses produced by subcellular fractionation of brain tissue. They contain the complete presynaptic terminal, including mitochondria and synaptic vesicles, and portions of the postsynaptic side, including the postsynaptic membrane and the postsynaptic density (PSyD). A proteomic characterisation of synaptosomes isolated from mouse brain was performed employing the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS/MS). After isotopic labelling and tryptic digestion, peptides were fractionated by cation exchange chromatography and cysteine-containing peptides were isolated by affinity chromatography. The peptides were identified by microcapillary liquid chromatography-electrospray ionisation MS/MS (muLC-ESI MS/MS). In two experiments, peptides representing a total of 1131 database entries were identified. They are involved in different presynaptic and postsynaptic functions, including synaptic vesicle exocytosis for neurotransmitter release, vesicle endocytosis for synaptic vesicle recycling, as well as postsynaptic receptors and proteins constituting the PSyD. Moreover, a large number of soluble and membrane-bound molecules serving functions in synaptic signal transduction and metabolism were detected. The results provide an inventory of the synaptic proteome and confirm the suitability of the ICAT method for the assessment of synaptic structure, function and plasticity.

Animals↗
PubMed1996

Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors.

1. Whole cell recordings of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the reticular formation were made from visualized hypoglossal motoneurons (HMs) in rat brain stem slices. 2. Carbachol, muscarine, or physostigmine reduced EPSC amplitude to 50 +/- 3%, 37 +/- 3%, and 54 +/- 7% (mean +/- SE) of control, respectively; effects of carbachol and physostigmine were antagonized by atropine (1-2 microM). EPSC depression was most effectively antagonized by methoctramine, an M2 muscarinic acetylcholine receptor (mAChR) antagonist with a high affinity constant (pKB) of 8.07 for the receptor mediating this response, whereas pirenzepine, an M1 mAChR antagonist, had a pKB of < 7.0, showing that EPSC depression was mediated by the M2 mAChR. 3. Postsynaptic properties of HMs (holding current and input resistance), EPSCs (reversal potential, rise time, half-width, and decay time constant), and postsynaptic glutamate-gated currents (amplitude and waveform) were not altered by carbachol or muscarine. 4. Muscarine did not decrease presynaptic neuron excitability, because the frequency of spontaneous EPSCs in HMs in the absence of tetrodotoxin (TTX) was either unchanged or increased. Leak and action currents of reticular formation neurons were not significantly altered by muscarine. In contrast, with TTX present, the frequency of spontaneous miniature glutamatergic EPSCs in HMs was decreased by both carbachol (mean change = 203 +/- 46%) and muscarine (mean change = 185 +/- 26%), with no change in miniature EPSC amplitude distribution. 5. Muscarinic depression of excitatory transmission to HMs thus occurs at the presynaptic terminal, most probably affecting release mechanisms downstream from calcium entry, and is likely to be significant during rapid eye movement sleep, possibly underlying the loss of tongue tone and inspiratory activity during this state.

Animals↗
PubMed1989

Localisation of chromogranin A and B, met-enkephalin-arg6-gly7-leu8 and PGP9.5-like immunoreactivity in the developing and adult rat adrenal medulla and extra-adrenal chromaffin tissue.

The localisation of chromogranins A and B, met-enkephalin-arg6-gly7-leu8 (met-enk 8) and protein gene product 9.5 (PGP 9.5) in the adrenal medulla and extra-adrenal chromaffin tissue has been studied in the developing rat by immunogold-silver staining. In the adult rat adrenal the cytoplasm of all medullary chromaffin cells showed a positive response with chromogranin A and B; in each case occasional groups of cells with a low reactivity that may have been NA cells were seen. Chromogranin A was first detected in adrenal medullary and extra-adrenal chromaffin cells at 18 days of gestation whilst chromogranin B was not detected in animals younger than 7 days. In 15 days old animals the adrenal medullary response to A and B was of the same intensity as that seen in the adult. Less than 1% of adult medullary chromaffin cells were responsive to met-enk 8 staining and medullary cells were unreactive in the fetus, with only extra-adrenal chromaffin tissue responding prenatally. During the first postnatal week immunoreactive cells appeared in the adrenal medulla in considerably greater proportions than in the adult gland. In contrast, positively stained nerve terminals associated with chromaffin cells and abundant in the adult adrenal were not detected during the first week of life. Immunoreactive nerve terminals were first seen early in the second week of life at a time when positive chromaffin cells were becoming less common. PGP 9.5 was located in all chromaffin cells of the adult adrenal and was readily detected in chromaffin cells in the adrenal and in extra-adrenal locations of the earliest stage examined (E16). Our findings suggest that the ontogenesis of the chromogranin-like immunostaining reflects the maturation of chromaffin granules and the PGP 9.5 immunostaining detected a protein common to cells of neuronal origin and expressed at an early stage of differentiation. The reciprocal relationship between the presence of enkephalins in chromaffin cells and in their presynaptic terminals merits further investigation.

Adrenal Medulla↗
PubMed1997

Differential distribution and subcellular localization of ryanodine receptor isoforms in the chicken cerebellum during development.

The distribution of ryanodine receptor (RyR) isoforms was examined using isoform-specific monoclonal antibodies in the developing chicken brain, from E18 through adulthood, using light and electron microscopic immunocytochemistry. Monoclonal antibody 110F is specific for the alpha-skeletal muscle form of RyR, while monoclonal antibody 110E recognizes both the beta-skeletal muscle and cardiac isoforms, but does not distinguish between the two. Significant differences in the distribution of the alpha- and beta/cardiac forms were observed. Labeling for the alpha-form was restricted to cerebellar Purkinje neurons while the beta/cardiac form was observed in neurons throughout the brain. A major finding was the presence of labeling for the beta/cardiac in presynaptic terminals of the parallel fibers in the molecular layer and the mossy fiber terminals in the granular layer glomeruli in late development and during adulthood. Labeling for the beta/cardiac, but not the alpha-form, underwent a major redistribution in the cerebellum during the course of development. At 1 day of age, beta/cardiac labeling was present mainly in Purkinje neurons. From 1 day to 4 weeks, immunolabeling for the beta/cardiac form gradually disappeared from Purkinje neurons, but increased in granule cells. Within the molecular layer, the labeling pattern changed from being primarily within Purkinje dendrites to a more diffuse pattern. Electron microscopic examination of the cerebellar molecular layer of 2-week-old chicks revealed that beta/cardiac-labeling was mainly present in the axons and presynaptic processes of the parallel fibers. No developmental changes were observed in other brain regions. This study represents the first demonstration of ryanodine receptor immunoreactivity in presynaptic boutons and suggests that the ryanodine receptor may modulate neurotransmitter release through local regulation of intracellular calcium in the parallel fiber synapse.

Animals↗
PubMed2001

Porocytosis: a new approach to synaptic function.

We propose a new approach to address the question of how a single quantum of neurotransmitter is secreted from a presynaptic terminal whose clustered secretory vesicles are locally bathed in high levels of calcium ions [Proceedings of the Symposium on Bioelectrogenesis (1961) 297-309; The Physiology of Synapses (1964) Chapters 1, 4, 5, 6; How the Self Controls its Brain (1994) Chapters 1, 4, 5, 6; Science 256 (1992) 677-679]. This hypothesis, which we term 'porocytosis', posits that the post-synaptic quantal response results from transmitter secreted through an array of docked vesicle/secretory pore complexes. The transient increase in calcium ions, which results from the voltage activated calcium channels, stimulates the array of secretory pores to simultaneously flicker open to pulse transmitter. Porocytosis is consistent with the quantal nature of presynaptic secretion and transmission, and with available biochemical, morphological and physiological evidence. It explains the frequency dependency of quantal size as a function of the secretion process. It permits a signature amount of transmitter release for different frequencies allowing a given synapse to be employed in different behavioral responses. The porocytosis hypothesis permits fidelity of secretion and the seemingly apposed characteristic of synaptic plasticity. The dynamics inherent in an array insure a constant quantal size as a function of the number of units within the array. In this hypothesis, plasticity is a consequence of concurrent pre- and post-synaptic changes due to a change in array size. Changes in the number of docked vesicle-secretory pore complexes composing the array can explain facilitation, depletion, graded excitation-secretion and long term plasticity.

Animals↗
PubMed2000

Reciprocal communication systems between astrocytes and neurones.

Over the past decade, a growing body of evidence has emerged on the existence in the brain of a close bidirectional communication system between neurones and astrocytes. This article reviews recent advances in understanding the rules governing these interactions and describes putative, novel functions attributable to astrocytes in neuronal transmission. Astrocytes can respond to the neurotransmitter released from active synaptic terminals, with cytosolic Ca(2+) oscillations whose frequency is under the dynamic control of neuronal activity. In response to these neuronal signals, astrocytes can signal back to neurones by releasing various neurone active compounds, such as the excitatory neurotransmitter glutamate. Interestingly, there is accumulating evidence that glutamate is released via a Ca(2+)-dependent mechanism which may share common properties with neurotransmitter exocytosis in neurones. This bidirectional communication system between neurones and astrocytes may lead to profound changes in neuronal excitability and synaptic transmission. While there clearly is an enormous amount of experimental and theoretical work yet to figure out, a coherent view is now emerging which incorporates the astrocyte, with the presynaptic terminal and the postsynaptic target neurone, as a possible third functional element of the synapse.

Animals↗