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Results for “Synaptic Transmission”

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At least 55 records · Page 3Linked to original sources

PubMed1999

Enhanced synaptic transmission and reduced threshold for LTP induction in fyn-transgenic mice.

To elucidate the physiological role of Fyn, we analysed the properties of synaptic transmission and synaptic plasticity in hippocampal slices of mice overexpressing either wild-type Fyn (w-Fyn) or its constitutively active mutant (m-Fyn). These fyn-transgenes were driven by the calcium/calmodulin-dependent protein kinase II alpha promoter which turned on in the forebrain neurons including hippocampal pyramidal cells and in late neural development. In the hippocampal slices expressing m-Fyn the paired-pulse facilitation was reduced and the basal synaptic transmission was enhanced. A weak theta-burst stimulation, which was subthreshold for the induction of long-term potentiation (LTP) in control slices, elicited LTP in CA1 region of the slices expressing m-Fyn. When a relatively strong stimulation was applied, the magnitude of LTP in m-Fyn slices was similar to that in control slices. By contrast, the basal synaptic transmission and the threshold for the induction of LTP were not altered in the slices overexpressing wild-type Fyn. To examine the effect of expression of m-Fyn on GABAergic inhibitory system, we applied bicuculline, a GABAA receptor blocker, to the hippocampal slices. The ability of bicuculline to enhance excitatory postsynaptic potentials was attenuated in slices expressing m-Fyn, suggesting that the overexpression of m-Fyn reduced the GABAergic inhibition. The enhancement of synaptic transmission and the reduction of GABAergic inhibition may contribute to the enhanced seizure susceptibility in the mice expressing m-Fyn. Thus, these results suggest that regulation of Fyn tyrosine kinase activity is important for both synaptic transmission and plasticity.

Animals↗

PubMed2006

CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission.

The genes encoding several synaptic proteins, including acetylcholine receptors, acetylcholinesterase, and the muscle-specific kinase, MuSK, are expressed selectively by a small number of myofiber nuclei positioned near the synaptic site. Genetic analysis of mutant mice suggests that additional genes, expressed selectively by synaptic nuclei, might encode muscle-derived retrograde signals that regulate the differentiation of motor axon terminals. To identify candidate retrograde signals, we used a microarray screen to identify genes that are preferentially expressed in the synaptic region of muscle, and we analyzed one such gene, CD24, further. We show that CD24, which encodes a small, variably and highly glycosylated, glycosylphosphatidylinositol (GPI)-linked protein, is expressed preferentially by myofiber synaptic nuclei in embryonic and adult muscle, and that CD24 expression is restricted to the central region of muscle independent of innervation. Moreover, we show that CD24 has a role in presynaptic differentiation, because synaptic transmission is depressed and fails entirely, in a cyclical manner, after repetitive stimulation of motor axons in CD24 mutant mice. These deficits in synaptic transmission, which are accompanied by aberrant stimulus-dependent uptake of AM1-43 from axons, indicate that CD24 is required for normal presynaptic maturation and function. Because CD24 is also expressed in some neurons, additional experiments will be required to determine whether pre- or postsynaptic CD24 mediates these effects on presynaptic development and function.

Animals↗

PubMed2005

Plasticity of synaptic transmission in autonomic ganglia.

Synaptic plasticity is a term that describes long-lasting changes in the efficacy of synaptic transmission resulting from certain patterned activities of the presynaptic nerve. One form of synaptic plasticity, long-term potentiation (LTP), is an activity-dependent marked increase in synaptic efficacy that has been extensively studied in various regions of the central nervous system, particularly the hippocampus, where LTP is widely believed to be a cellular correlate of learning and memory. A similar phenomenon has been identified in sympathetic ganglia even before Bliss and Lomo coined the term LTP in 1973. Ganglionic LTP (gLTP) of the nicotinic pathway is a similarly long-lasting increase in synaptic effectiveness that can be induced in ganglia following a brief train of relatively high frequency stimulation (HFS) of the preganglionic nerve. Remarkably similar to the LTP of the hippocampus, gLTP has been demonstrated in autonomic ganglia from a number of vertebrates including mammalian, amphibian and avian species. Several other forms of long-lasting increases in synaptic effectiveness have been demonstrated in sympathetic ganglia following exposure to adrenergic agonists, neuroactive peptides and cyclic nucleotides and even after a challenge by an antigen. The main emphasis of this review, however, will be on the activity-dependent gLTP of the mammalian sympathetic ganglia, in particular the superior cervical ganglion of the rat. Since the last, excellent and comprehensive review of this ganglionic function by Briggs in 1995, important discoveries about the mechanisms of induction and maintenance of gLTP have been reported, including the finding that the response is uniquely dependent on serotonin for both the induction phase and maintenance phase. These new advances will be discussed in depth in this review.

Animals↗

PubMed1994

An evaluation of causes for unreliability of synaptic transmission.

Transmission at individual synaptic contacts on CA1 hippocampal pyramidal neurons has been found to be very unreliable, with greater than half of the arriving presynaptic nerve impulses failing to evoke a postsynaptic response. This conclusion has been reached using the method of minimal stimulation of Schaffer collaterals and whole cell recording in hippocampal slices; with minimal stimulation only one or a few synapses are activated on the target neuron and the behavior of individual synapses can be examined. Four sources for the unreliability of synaptic transmission have been investigated: (i) the fluctuation of axon thresholds at the site of stimulation causing the failure to generate a nerve impulse in the appropriate Schaffer collaterals, (ii) the failure of nerve impulses generated at the site of stimulation to arrive at the synapse because of conduction failures at axon branch points, (iii) an artifactual synaptic unreliability due to performing experiments in vitro at temperatures well below the normal mammalian body temperature, and (iv) transmission failures due to probabilistic release mechanisms at synapses with a very low capacity to release transmitter. We eliminate the first three causes as significant contributions and conclude that probabilistic release mechanisms at low capacity synapses are the main cause of unreliability of synaptic transmission.

Animals↗

PubMed2004

Age-dependence in the homeostatic upregulation of hippocampal dendritic spine number during blocked synaptic transmission.

Homeostatic regulation of spine number in mature hippocampal neurons results in more dendritic spines when synaptic transmission is blocked, providing a mechanism to compensate for diminished synaptic input. It is unsettled whether blockade of synaptic transmission also elevates spine number during development. To address this question, synaptic transmission was blocked in rat hippocampal slices during critical developmental stages of spine formation at postnatal days (P) 6-P22 and compared to adults. CA1 pyramidal cells were labeled with DiI and maintained for 5 h in one of three conditions, control artificial cerebrospinal fluid (ACSF), block media containing synaptic transmission antagonists in ACSF, or block media containing synaptic transmission antagonists in a nominally calcium-free ACSF with high magnesium. Slices were fixed in mixed aldehydes, sectioned, and the lateral dendrites were imaged in stratum radiatum with confocal microscopy. Dendritic spine density was quantified per unit length of dendrite. At P6-7 there were only a few protrusions emerging from the dendrites, which were predominantly filopodia-like in appearance. At both P11-12 and P15-16 there was a mixture of dendritic spines and filopodia-like structures. By P20-22 dendritic spines predominated and spine density was about 82% of the adult level. Dendritic spine density increased during blocked synaptic transmission at P20-22 as in adults, but was unchanged during blockade at younger ages. When extracellular calcium was nominally zero, dendritic spine density further increased on P20-22 dendrites as in adults. In contrast, spine density decreased along P11-12 dendrites under the nominally zero calcium condition. Under control conditions, dendritic protrusions were longer at P6-7 than at all other ages, which did not differ from one another. When synaptic transmission was blocked, dendritic protrusions further elongated at P6-7 only. Under the nominally zero calcium condition with blocked synaptic transmission, dendritic protrusions shortened at P11-12 only. These findings reveal age-dependent changes in the manifestation of homeostatic control of dendritic spines that could be mediated by maturational changes in mechanisms regulating postsynaptic calcium.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2003

Variance-mean analysis: a simple and reliable approach for investigating synaptic transmission and modulation.

The mechanisms underlying synaptic plasticity can be investigated by analyzing synaptic amplitude fluctuations before and after a synaptic modulation. However, many older fluctuation analysis techniques rely on models of synaptic transmission that incorporate unrealistic simplifying assumptions or have too many free parameters. As a result, these techniques have sometimes produced counterintuitive or contradictory results. In contrast, the variance-mean (V-M) technique requires fewer assumptions and is more robust than previous approaches. It achieves these improvements by focusing on two key parameters of synaptic transmission, the average probability that a vesicle is released from a synaptic terminal following a presynaptic stimulus (Pav), and the average amplitude of the postsynaptic response to a vesicle of transmitter (Qav). To apply V-M analysis, a fluctuating postsynaptic current (PSC) is recorded at several different extracellular Ca2+ or Cd2+ concentrations. The variance of the PSC amplitude is plotted against the mean amplitude at each concentration, forming a parabola. The degree of parabolic curvature estimates Pav, and the limiting slope under low release conditions estimates Qav. The shape of the V-M parabola changes in characteristic ways following each of the three standard forms of synaptic modulation: a change in Qav (postsynaptic), a change in Pav (presynaptic), or a change in the number of terminals (N). The approach does not require specialized software, and can even be implemented as a purely graphical technique. V-M analysis has been used to investigate the site of expression of long-term potentiation and the mechanisms underlying paired-pulse depression. This report presents a detailed mathematical development of the technique, and explores the limiting conditions under which it can confidently be applied. V-M analysis requires fewer than 100 PSC amplitude measurements to accurately estimate Pav and Qav, and it can reliably identify whether a synaptic modulation occurs at a pre- or postsynaptic site. In contrast to other techniques, V-M analysis is largely insensitive to recording noise, nonuniform modulation and intrinsic variability of the unitary synaptic amplitude.

Algorithms↗

PubMed2005

Delta(9)-Tetrahydrocannabinol-induced desensitization of cannabinoid-mediated inhibition of synaptic transmission between hippocampal neurons in culture.

Prolonged exposure to cannabinoids results in desensitization of cannabinoid receptors. Here, we compared the desensitization produced by the partial agonist, Delta(9)-tetrahydrocannabinol (THC) to that produced by the full agonist Win55,212-2 on cannabinoid-mediated inhibition of glutamatergic synaptic transmission. Synaptic activity between rat hippocampal neurons was determined from network-driven increases in the intracellular Ca(2+) concentration ([Ca(2+)](i) spikes). To assess the effects of prolonged treatment, cultures were incubated with cannabinoids, washed in 0.5% fatty-acid-free bovine serum albumin to ensure the removal of the lipophilic drug and then tested for inhibition of [Ca(2+)](i) spiking by Win55,212-2. In control experiments, 0.1 microM Win55,212-2 inhibited [Ca(2+)](i) spiking by 93 +/- 5%. Win55,212-2 produced significantly less inhibition of [Ca(2+)](i) spiking following 18-24h treatment with 1 microM THC (48 +/- 5%) or treatment with 1 microM Win55,212-2 (29 +/- 6%). Thus, THC produced significantly less functional desensitization than Win55,212-2. The desensitization produced by THC was maximal at 0.3 microM, remained stable between 1 and 7 days of preincubation and shifted the EC(50) of acute inhibition by Win55,212-2 from 27 to 251 nM. Differences in the long-term effects of cannabinoid receptor agonists on synaptic transmission may prove important for evaluating their therapeutic and abuse potential.

Animals↗

PubMed2000

Presynaptic inhibitory receptors mediate the depression of synaptic transmission upon hypoxia in rat hippocampal slices.

Hypoxia markedly depresses synaptic transmission in hippocampal slices of the rat. This depression is attributed to presynaptic inhibition of glutamate release and is largely mediated by adenosine released during hypoxia acting through presynaptic adenosine A(1) receptors. Paired pulse facilitation studies allowed us to confirm the presynaptic nature of the depression of synaptic transmission during hypoxia. We tested the hypothesis that activation of heterosynaptic inhibitory receptors localized in glutamatergic presynaptic terminals in the hippocampus, namely gamma-aminobutyric acid subtype B (GABA(B)) receptors, alpha(2)-adrenergic receptors, and muscarinic receptors might contribute to the hypoxia-induced depression of synaptic transmission. Field excitatory postsynaptic potentials were recorded in the CA1 area of hippocampal slices from young adult (5-6 weeks) Wistar rats. Neither the selective antagonist for alpha(2)-adrenergic receptors, rauwolscine (10 microM), nor the antagonist for the GABA(B) receptors, CGP 55845 (10 microM), modified the response to hypoxia. The selective adenosine A(1) receptor antagonist, DPCPX (50 nM), reduced the hypoxia-induced depression of synaptic transmission to 59.2+/-9.6%, and the muscarinic receptor antagonist, atropine (10 microM), in the presence of DPCPX (50 nM), further attenuated the depression of synaptic transmission to 49.4+/-8.0%. In the same experimental conditions, in the presence of DPCPX (50 nM), the muscarinic M(2) receptor antagonist AF-DX 116 (10 microM), but not the M(1) receptor antagonist pirenzepine (1 microM), also attenuated the hypoxia-induced depression to 41.6+/-6.6%. Activation of muscarinic M(2) receptors contributes to the depression of synaptic transmission upon hypoxia. This effect should assume particular relevance during prolonged periods of hypoxia when other mechanisms may become less efficient.

Animals↗

PubMed1998

Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent to the broadening effect of lithium on the action potential.

Action Potentials↗

PubMed2003

Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain.

Synaptic activation is associated with rapid changes in intracellular Ca(2+), while the extracellular Ca(2+) level is generally assumed to be constant. Here, using a novel optical method to measure changes in extracellular Ca(2+) at high spatial and temporal resolution, we find that brief trains of synaptic transmission in hippocampal area CA1 induce transient depletion of extracellular Ca(2+). We show that this depletion, which depends on postsynaptic NMDA receptor activation, decreases the Ca(2+) available to enter individual presynaptic boutons of CA3 pyramidal cells. This in turn reduces the probability of consecutive synaptic releases at CA3-CA1 synapses and therefore contributes to short-term paired-pulse depression of minimal responses. This activity-dependent depletion of extracellular Ca(2+) represents a novel form of fast retrograde synaptic signaling that can modulate glutamatergic information transfer in the brain.

Animals↗

PubMed2005

Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.

Adaptor Protein Complex 2↗

PubMed2001

The effects of the bacterial endotoxin lipopolysaccharide on synaptic transmission and plasticity in the CA1-subiculum pathway in vivo.

Lipopolysaccharide is derived from the cell wall of gram-negative bacteria and is a potent endotoxin which causes the release of cytokines in the CNS. We examined the effect of lipopolysaccharide on synaptic transmission and synaptic plasticity in the hippocampal area CA1-subicular pathway in vivo. We found that lipopolysaccharide did not affect baseline synaptic transmission in this pathway; it did, however, reduce the magnitude of paired-pulse facilitation, a form of short-term plasticity thought to be primarily presynaptic in origin. We then examined the interaction between lipopolysaccharide and two common models for the biological basis of memory: high-frequency stimulation induced long-term potentiation and low-frequency stimulation induced long-term depression of synaptic transmission. We found that lipopolysaccharide blocked long-term potentiation following high-frequency stimulation and also induced potentiation of synaptic transmission after low-frequency stimulation. Lipolysaccharide blocked paired-pulse facilitation selectively at short rather than longer interstimulus intervals. Thus, lipopolysaccharide has different effects on synaptic transmission in this pathway depending on the frequency and length of stimulation. These results provide new insights into the action of lipopolysaccharide on various forms of plasticity in the hippocampus, an area known to play a vital role in learning and memory.

Animals↗

PubMed2006

Spike-mediated and graded inhibitory synaptic transmission between leech interneurons: evidence for shared release sites.

Inhibitory synaptic transmission between leech heart interneurons consist of two components: graded, gated by Ca2+ entering by low-threshold [low-voltage-activated (LVA)] Ca channels and spike-mediated, gated by Ca2+ entering by high-threshold [high-voltage-activated (HVA)] Ca channels. Changes in presynaptic background Ca2+ produced by Ca2+ influx through LVA channels modulate spike-mediated transmission, suggesting LVA channels have access to release sites controlled by HVA channels. Here we explore whether spike-mediated and graded transmission can use the same release sites and thus how Ca2+ influx by HVA and LVA Ca channels might interact to evoke neurotransmitter release. We recorded pre- and postsynaptic currents from voltage-clamped heart interneurons bathed in 0 mM Na+/5 mM Ca2+ saline. Using different stimulating paradigms and inorganic Ca channel blockers, we show that strong graded synaptic transmission can occlude high-threshold/spike-mediated synaptic transmission when evoked simultaneously. Suppression of LVA Ca currents diminishes graded release and concomitantly increases the ability of Ca2+ entering by HVA channels to release transmitter. Uncaging of Ca chelator corroborates that graded release occludes spike-mediated transmission. Our results indicate that both graded and spike-mediated synaptic transmission depend on the same readily releasable pool of synaptic vesicles. Thus Ca2+, entering cells through different Ca channels (LVA and HVA), acts to gate release of the same synaptic vesicles. The data argue for a closer location of HVA Ca channels to release sites than LVA Ca channels. The results are summarized in a conceptual model of a heart interneuron release site.

Action Potentials↗

PubMed2004

Adrenoceptor subtype-specific acceleration of the hypoxic depression of excitatory synaptic transmission in area CA1 of the rat hippocampus.

The depression of excitatory synaptic transmission by hypoxia in area CA1 of the hippocampus is largely dependent upon the activation of adenosine A(1) receptors on presynaptic glutamatergic terminals. As well as adenosine, norepinephrine levels increase in the hypoxic/ischemic hippocampus. We sought to determine the influence of alpha- and beta-adrenoceptor (AR) activation on the hypoxic depression of synaptic transmission utilizing electrophysiological, pharmacological and adenosine sensor techniques. Norepinephrine depressed synaptic transmission and significantly accelerated the hypoxic depression of synaptic transmission. The alpha-AR agonist 6-fluoronorepinephrine mimicked both of these effects whilst the alpha(2)-AR antagonist yohimbine, but not the alpha(1)-AR antagonist urapidil, prevented the actions of 6-fluoronorepinephrine. In contrast, the beta-AR agonist isoproterenol enhanced synaptic transmission and only accelerated the hypoxic depression of transmission in hypoxia-conditioned slices in which the hypoxic release of adenosine is reduced. The effects of isoproterenol were blocked by the non-selective beta-AR antagonist propranolol and the selective beta(1)-AR antagonist betaxolol. Using an enzyme-based adenosine sensor we observed that the application of the beta-AR agonist resulted in increased extracellular adenosine during repeated hypoxia. Our results suggest that alpha(2)-AR activation facilitates the hypoxic depression of synaptic transmission probably via the known alpha(2)-AR-mediated inhibition of presynaptic calcium channels whereas beta(1)-AR activation does so via increased extracellular adenosine and greater activation of inhibitory adenosine A(1) receptors.

Adenosine↗

PubMed1982

Boutons originating from the same axon do not participate equally in synaptic transmission.

Morphological changes in the synaptic boutons located on the ciliary neurons were observed following stimulation of the Edinger-Westphal nucleus (EWn). A reduction in the number of clear and dense core vesicles (DCVs) per unit area and an increased surface density of vacuoles were observed in boutons located proximal to the afferent axon. Only a slight reduction in the number of DCVs per unit area was observed on boutons located distally to the afferent axon. Several mechanisms are proposed to explain why all boutons do not participate equally in synaptic transmission.

Animals↗

PubMed2002

The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo.

Synaptotagmin is a synaptic vesicle protein that is postulated to be the Ca(2+) sensor for fast, evoked neurotransmitter release. Deleting the gene for synaptotagmin (syt(null)) strongly suppresses synaptic transmission in every species examined, showing that synaptotagmin is central in the synaptic vesicle cycle. The cytoplasmic region of synaptotagmin contains two C(2) domains, C(2)A and C(2)B. Five, highly conserved, acidic residues in both the C(2)A and C(2)B domains of synaptotagmin coordinate the binding of Ca(2+) ions, and biochemical studies have characterized several in vitro Ca(2+)-dependent interactions between synaptotagmin and other nerve terminal molecules. But there has been no direct evidence that any of the Ca(2+)-binding sites within synaptotagmin are required in vivo. Here we show that mutating two of the Ca(2+)-binding aspartate residues in the C(2)B domain (D(416,418)N in Drosophila) decreased evoked transmitter release by >95%, and decreased the apparent Ca(2+) affinity of evoked transmitter release. These studies show that the Ca(2+)-binding motif of the C(2)B domain of synaptotagmin is essential for synaptic transmission.

Amino Acid Motifs↗

PubMedDate not supplied

Perinatal nutritional iron deficiency reduces hippocampal synaptic transmission but does not impair short- or long-term synaptic plasticity.

Studies show that perinatal nutritional iron deficiency (ID) produces learning and memory impairments in humans and animals. This suggests that the functional physiology of learning and cognitive centers in the brain, such as the hippocampus, may be compromised by developmental ID. The present study used electrophysiological brain slice methods to examine multiple measures of hippocampal synaptic efficacy from rats that were subjected to perinatal ID diets or control (CN) diets. Measures of synaptic efficacy were obtained from the first and last synaptic regions of the hippocampal tri-synaptic loop (i.e. the dentate gyrus (DG) and CA1). Rats were placed on ID or CN diets on gestational day 11, and hippocampal brain slices were prepared between postnatal day 25 and 37. Results show that ID slices were not impaired in short-term (i.e. paired-pulse facilitation (PPF)) or long-term measures (i.e. long-term potentiation (LTP)) of synaptic plasticity in either the DG or CA1 areas. Input-output (IO) measures showed that synaptic transmission was reduced in both of these areas in the ID slices when compared with the CN slices. This suggests that ID-induced learning deficits may be the result of reductions in synaptic transmission throughout the hippocampus, and possibly in other learning and memory centers.

Anemia, Iron-Deficiency↗

PubMed2004

Synaptic vesicle pools and plasticity of synaptic transmission at the Drosophila synapse.

Our knowledge on the Drosophila neuromuscular synapse is rapidly expanding. Thus, this synapse offers an excellent model for studies of the molecular mechanism of synaptic transmission and synaptic plasticity. Two synaptic vesicle (SV) pools have been identified and characterized using a fluorescent styryl dye, FM1-43, to stain SVs. They are termed the exo/endo cycling pool (ECP), which corresponds to the readily releasable pool (RRP) defined electrophysiologically, and the reserve pool (RP). These two pools were identified first in a temperature-sensitive paralytic mutant, shibire, and subsequently confirmed in wild-type larvae. The ECP participates in synaptic transmission during low frequency firing of presynaptic nerves and locates in the periphery of presynaptic boutons in the vicinity of release sites, while SVs in the RP spread toward the center of boutons and are recruited only during tetanic stimulation. These two pools are separately replenished by endocytosis. Cyclic AMP facilitates recruitment of SVs from the RP to the ECP. Activation of presynaptic metabotropic glutamate receptors recruits SVs from the RP and enhances SV release by elevation of the cAMP level. Memory mutants that have defects in the cAMP/PKA cascade, dunce and rutabaga, exhibit reduced levels of recruitment of synaptic SVs from the RP to the ECP and have limited short-term synaptic plasticity. SV mobilization between the two pools could be a key step for changes in synaptic efficacy. Since a variety of mutants that have distinct defects in synaptic transmission are available for detailed studies of synaptic function, this direction of approach in Drosophila seems promising.

Animals↗