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PubMed1999

Can GAP-43 interact with brain spectrin?

The growth-associated and presynaptic protein GAP-43 is important for axonal growth during brain development, for synaptic plasticity and in axonal regeneration [Benowitz, Routtenberg, TINS 12 (1987) 527]. It has been speculated that such growth may be mediated by cytoskeletal proteins. However, the interaction of GAP-43 with proteins of the presynaptic terminals is poorly characterized. Here, we analyze GAP-43 binding to cytoskeletal proteins by two different biochemical assays, by blot overlay and sedimentation. We find that immobilized brain spectrin (BS) is able to bind GAP-43. In contrast, little binding was observed to microtubule proteins and other elements of the cytoskeleton. Since GAP-43 is located presynaptically, it may bind to the presynaptic form of BS (SpIISigma1). It is attractive to think that such an interaction would participate in the structural plasticity observed in growth cones and adult synapses.

Animals↗
PubMed1997

Effects of cocaine treatment on the nervous system of planaria (Dugesia gonocephala s. l.). Histochemical and ultrastructural observations.

Acute high dose treatment with cocaine in planaria has been shown to produce hyperkinesia followed by immobilization, thus suggesting progressive neuronal dopamine (DA) depletion. On the contrary, treatment with low doses of cocaine inhibits motor activity in planaria, without producing hyperkinesias. Here we investigated the morpho-functional changes of the DA presynaptic terminals following cocaine treatment in planaria (acute high dose and chronic low dose). Neuronal DA content was determined by means of histochemical methods, and nerve cell ultrastructure was examined by electron microscopy. The effects of cocaine were compared to those of L-dopa, reserpine (used as positive and negative controls, respectively) and normal untreated specimens. Presynaptic vesicles and DA content were significantly reduced by chronic low-dose cocaine treatment. These effects were even more robust when the drug was acutely administered at high dose. Thus, depletion of DA vesicles is produced by cocaine in planaria, as well as in mammals. The behavioral effects of chronic low-dose treatment with cocaine, however, suggest that the drug acts not only as a DA reuptake blocker, but also as a direct agonist on presynaptic DA receptors. Acute high-dose administration of cocaine also produced signs of neuronal suffering, thus providing evidence for a direct neurotoxic effect of the drug.

Animals↗
PubMed1981

Effects of ouabain and electrical stimulation on the fine structure of nerve endings in the electric organ of Torpedo marmorata.

The cycle of synaptic vesicles was studied in isolated nerve terminals and in the electric tissue of Torpedo marmorata. The synaptosomes, as used in this investigation, were a pure cholinergic subcellar fraction that captured dextran particles as an extracellular marker. This endocytotic phenomenon was enhanced by potassium depolarization. Field electrical stimulation (1 Hz and 10 Hz) of the electric organ induced the appearance of membrane foldings into presynaptic terminals. Morphometric studies showed that the number of synaptic vesicles did not decline until after at least 30 min. On the other hand, at 10 Hz these changes were accompanied by an increase in length of the membrane of the terminal. At 15 min of recovery after prolonged stimulation, there was a great increase in density of synaptic vesicles with a large number of vesicles of small diameter. This increase was accompanied by a decrease of membrane length, suggesting that reformation of vesicles is related to retrieval of membrane. Pharmacological stimulation with ouabain produced changes similar to those of long-term electrical stimulation. These changes in membrane were accompanied by a decrease of the population of synaptic vesicles and a wide variation in their diameters. It is concluded that structural changes reported here could not be correlated with kinetics of the transmitter release.

Animals↗
PubMed1989

Ultrastructural localization of choline acetyltransferase in the rat rostral ventrolateral medulla: evidence for major synaptic relations with non-catecholaminergic neurons.

Pharmacological and biochemical studies suggest that interactions between cholinergic and catecholaminergic and catecholaminergic neurons, particularly those of the C1 adrenergic cell group, in the rostral ventrolateral medulla (RVL) may be important in cardiovascular control. Ultrastructural localization of choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine, and its relation to neurons exhibiting immunoreactivity for catecholamine- (tyrosine hydroxylase; TH) or adrenaline (phenylethanolamine-N-methyltransferase; PNMT) -synthesizing enzymes were examined in the RVL using dual immunoautoradiographic and peroxidase anti-peroxidase (PAP) labeling methods. By light microscopy, the ChAT-immunoreactive neurons were located both dorsally (i.e. the nucleus ambiguus) and ventromedially to those labeled with TH or PNMT (TH/PNMT). A few ChAT-labeled processes were dispersed among TH/PNMT-containing neurons with the majority of overlap immediately ventral to the nucleus ambiguus. By electron microscopy, ChAT-immunoreactivity (ChAT-I) was detected in neuronal perikarya, dendrites, axons and axon terminals and in the vascular endothelial cells of certain blood vessels. The ChAT-labeled perikarya in the ventromedial RVL were medium-sized (15-20 microns), elongated, contained abundant cytoplasm and had had slightly indented nuclei. Synaptic junctions on ChAT-immunoreactive perikarya and dendrites were primarily symmetric with 64% (45 out of 70) of the presynaptic terminals unlabeled. The remaining terminals were immunoreactive for ChAT (30%) or TH/PNMT (6%). Terminals with ChAT-I were large (0.8-2.0 microns) and contained numerous small clear vesicles and 1-2 dense core vesicles. Seventy-seven percent (112 out of 145) of the ChAT-labeled terminals formed symmetric synapses with unlabeled perikarya and dendrites, whereas only 8% were with TH/PNMT-labeled perikarya and dendrites, and 15% were with ChAT-immunoreactive perikarya and dendrites. We conclude (1) that cholinergic neurons in the RVL principally terminate on and receive input from non-catecholaminergic neurons, and (2) that the reported sympathetic activation following application of cholinergic agents to the RVL may be mediated by cholinergic inhibition of local inhibitory interneurons. The observed synapses between ChAT and TH/PNMT-containing neurons suggests that cholinergic and adrenergic neurons additionally may exert a minor reciprocal control on each other and thus may modulate their response to the more abundant input from afferents containing other transmitters.

Animals↗
PubMed2006

The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development.

The formation and plasticity of synaptic connections rely on regulatory interactions between pre- and postsynaptic cells. We show that the Drosophila heparan sulfate proteoglycans (HSPGs) Syndecan (Sdc) and Dallylike (Dlp) are synaptic proteins necessary to control distinct aspects of synaptic biology. Sdc promotes the growth of presynaptic terminals, whereas Dlp regulates active zone form and function. Both Sdc and Dlp bind at high affinity to the protein tyrosine phosphatase LAR, a conserved receptor that controls both NMJ growth and active zone morphogenesis. These data and double mutant assays showing a requirement of LAR for actions of both HSPGs lead to a model in which presynaptic LAR is under complex control, with Sdc promoting and Dlp inhibiting LAR in order to control synapse morphogenesis and function.

Animals↗
PubMed2001

Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse.

1. Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse. 2. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA. 3. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs. 4. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA. 5. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal.

Action Potentials↗
PubMed1981

On the calcium receptor that mediates depolarization-secretion coupling at cholinergic motor nerve terminals.

1 The behaviour of the divalent cations Ca and Sr as agonists for receptors that mediate the synchronous evoked secretion of acetylcholine (ACh) was studied in the hope of determining whether the relationship between Ca binding and ACh secretion is determined only by the law of mass action or by the mathematical framework of receptor theory. Experiments were designed to evaluate the assumption that maximum effect requires occupation of all receptors by testing for the presence of spare Ca receptors on presynaptic terminals. Frog cutaneous nerve-muscle preparations were employed in conjunction with conventional electrophysiological methods.2 Curves of log [Ca] or log [Sr] against the mean number of ACh quanta released (m) were constructed to saturation. The log [Sr]-m relationship was shifted to the right and had a smaller maximum than the log [Ca]-m curve. This suggests that Ca has a higher efficacy than Sr and raises the possibility that spare binding sites are present for Ca.3 As a qualitative test for spare Ca receptors, La(3+) (>/=0.5 mum) or 2-chloroadenosine (25 mum) was employed as an irreversible antagonist of the effects of extracellular Ca on evoked ACh release. Despite the irreversible blockade of a proportion of receptors, increases in the [Ca] overcame this antagonism and produced a parallel shift in the log [Ca]-m relation to the right. This suggests an apparent receptor reserve for Ca. Antagonism of Sr-mediated ACh release by either La(3+) or 2-chloroadenosine could not be overcome by increasing the [Sr].4 As a quantitative test for spare Ca binding sites, the equilibrium affinity constant for Sr(K(Sr)) as a competitive inhibitor of Ca was determined and compared with values for K(Sr) calculated by two other methods which invoke the spare receptor assumption. All three methods produced comparable results. (K(Sr) = 0.24-0.27 mm(-1)).5 The equilibrium affinity constant for Ca (K(Ca)) was calculated by comparing reciprocal plots of the concentrations of Ca that produce equal levels of ACh release in the presence and absence of La(3+) (0.5 mum-3 mum). K(Ca) was estimated to be between 0.02 and 0.06 mm(-1).6 Efficacy (e), which is thought to reflect the ability of Ca or Sr once bound to receptors to support ACh release, was determined by the modified occupation theory of Stephenson (1956). The e(Ca) was estimated to be 9-20 and e(Sr) was 0.2-0.5.7 The experimentally determined values for K(Ca), K(Sr), e(Ca), e(Sr) along with the assumptions that spare Ca binding sites exist and that the non-linearities in the log [Ca] or log [Sr]-m curves are introduced beyond the sites of binding and efficacy were used to generate theoretical log [Me]-m curves. The theoretical relationships were similar to the experimental results.8 The results suggest that spare Ca receptors are present at motor nerve endings and that receptor theory provides an accurate quantitative description of the lumped events between Ca binding and ACh secretion. The possible physical correlates of affinity and efficacy are discussed.

Animals↗
PubMed1998

Long-term potentiation and dual-component quantal signaling in the dentate gyrus.

Long-term potentiation (LTP) of excitatory transmission is an important candidate cellular mechanism for the storage of memories in the mammalian brain. The subcellular phenomena that underlie the persistent increase in synaptic strength, however, are incompletely understood. A potentially powerful method to detect a presynaptic increase in glutamate release is to examine the effect of LTP induction on the rate at which the use-dependent blocker MK-801 attenuates successive N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic signals. This method, however, has given apparently contradictory results when applied in hippocampal CA1. The inconsistency could be explained if NMDA receptors were opened by glutamate not only released from local presynaptic terminals, but also diffusing from synapses on neighboring cells where LTP was not induced. Here we examine the effect of pairing-induced LTP on the MK-801 blocking rate in two afferent inputs to dentate granule cells. LTP in the medial perforant path is associated with a significant increase in the MK-801 blocking rate, implying a presynaptic increase in glutamate release probability. An enhanced MK-801 blocking rate is not seen, however, in the lateral perforant path. This result still could be compatible with a presynaptic contribution to LTP in the lateral perforant path if intersynaptic cross-talk occurred. In support of this hypothesis, we show that NMDA receptors consistently sense more quanta of glutamate than do alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the medial perforant path, in contrast, there is no significant difference in the number of quanta mediated by the two receptors. These results support a presynaptic contribution to LTP and imply that differences in intersynaptic cross-talk can complicate the interpretation of experiments designed to detect changes in transmitter release.

Animals↗
PubMed1994

Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex.

The cerebral cortices of macaques (ranging in age from 10 to 37 years; n = 17) were analyzed by immunocytochemistry and electron microscopy to determine the cellular and subcellular localizations of the amyloid precursor protein and beta-amyloid protein, the cellular participants in the formation of senile plaques and parenchymal deposits of the beta-amyloid protein, and the temporal/spatial development of these lesions. Amyloid precursor protein was enriched within the cytoplasm of pyramidal and nonpyramidal neuronal cell bodies in young and old monkeys. In the neuropil, amyloid precursor protein was most abundant within dendrites and dendritic spines; few axons, axonal terminals, and resting astrocytes and microglia contained the amyloid precursor protein. At synapses, amyloid precursor protein was found predominantly within postsynaptic elements and was enriched at postsynaptic densities of asymmetrical synapses. The earliest morphological change related to senile plaque formation was an age-related abnormality in the cortical neuropil characterized by the formation of dense bodies within presynaptic terminals and dendrites and an augmented localization of the amyloid precursor protein to astrocytes and microglia. In most monkeys > 26 years of age, the neocortical parenchyma exhibited neuritic pathology and plaques characterized by swollen cytoplasmic processes, interspersed somata of neurons, and reactive glia within or at the periphery of senile plaques. Neurites and reactive astrocytes and microglia within these plaques were enriched with the amyloid precursor protein. In diffuse plaques, nonfibrillar beta-amyloid protein immunoreactivity was visualized within cytoplasmic lysosomes of neuronal perikarya and dendrites and the cell bodies and processes of activated astrocytes and microglia. In mature plaques, beta-amyloid protein immunoreactivity was associated with extracellular fibrils within the parenchyma; some cytoplasmic membranes of degenerating dendrites and somata as well as processes of activated glia showed diffuse intracellular beta-amyloid protein immunoreactivity. We conclude that morphological abnormalities at synapses (including changes in both pre- and postsynaptic elements) precede the accumulation of the amyloid precursor protein within neurites and activated astrocytes and microglia as well as the deposition of extracellular fibrillar beta-amyloid protein; neuronal perikarya/dendrites and reactive glia containing the amyloid precursor protein are primary sources of the beta-amyloid protein within senile plaques; and nonfibrillar beta-amyloid protein exists intracellularly within neurons and nonneuronal cells prior to the appearance of extracellular deposits of the beta-amyloid protein and the formation of beta-pleated fibrils.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1997

Presynaptic inhibition compared with homosynaptic depression as an explanation for soleus H-reflex depression in humans.

The H-reflex is depressed for seconds if elicited following a single H-reflex or train of H-reflexes. Presynaptic inhibition from flexor afferents (tibialis anterior) onto soleus Ia afferents elicited by either single or trains of stimuli had no effect on the soleus H-reflex on a time scale of seconds. Postsynaptic inhibition was also excluded by magnetic stimulation tests that showed that the excitability of the motoneuron pool was not changed at latencies within a range of seconds. Homosynaptic depression localized at the presynaptic terminal seems to be the mechanism behind the H-reflex depression in humans.

Adult↗
PubMed1991

Localization of the inositol 1,4,5-trisphosphate receptor in synaptic terminals in the vertebrate retina.

Inositol 1,4,5-trisphosphate (InsP3) mobilizes internal Ca2+ in cells by binding to a receptor protein, which has recently been purified and molecularly cloned. To clarify those neuronal functions that are regulated by InsP3, we have localized this InsP3 receptor protein immunocytochemically in the retina, a neural tissue of well-defined structure and function. Positive staining in neurons is confined almost exclusively to the synaptic layers. Using dissociated retinal neurons, we have further localized the receptor to presynaptic terminals of photoreceptors and bipolar cells, as well as the synaptic processes of amacrine cells. The specific association of InsP3 receptors with synaptic terminals suggests a role for InsP3 in synaptic modulation, especially with respect to transmitter release.

Ambystoma↗
PubMed2000

Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation.

Two days of monocular deprivation (MD) of kittens during a critical period of development is known to produce a loss of visual responses in the primary visual cortex to stimulation of the nondeprived eye, and 7 days of deprivation results in retraction of axon branches and loss of presynaptic sites from deprived-eye geniculocortical arbors. The rapid loss of responsiveness to deprived-eye visual stimulation could be due to a decrease in intracortical excitatory input to deprived-eye ocular dominance columns (ODCs) relative to nondeprived-eye columns. Alternatively, deprived-eye visual responses could be suppressed by an increase in intracortical inhibition in deprived columns relative to nondeprived columns. We tested these hypotheses in critical period kittens by labeling ODCs in layer IV of primary visual cortex with injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into lamina A of the lateral geniculate nucleus (LGN). After either 2 or 7 days of MD, densities of intracortical excitatory presynaptic sites within deprived relative to nondeprived ODCs were estimated by measuring synaptic vesicle protein (SVP) immunoreactivity (IR). Because most of the synapses within layer IV of primary visual cortex are excitatory inputs from other cortical neurons, levels of SVP-IR provide an estimate of the amount of intracortical excitatory input. We also measured levels of immunoreactivity of the inhibitory presynaptic terminal marker glutamic acid decarboxylase (GAD)65 in deprived relative to nondeprived ODCs. Monocular deprivation (either 2 or 7 days) had no effect on the distributions of either SVP- or GAD65-IR in deprived and nondeprived columns. Therefore, the rapid loss of deprived-eye visual responsiveness following MD is due neither to a decrease in intracortical excitatory presynaptic sites nor to an increase in intracortical inhibitory presynaptic sites in layer IV of deprived-eye ODCs relative to nondeprived columns.

Animals↗
PubMed1991

Pre- and postsynaptic alpha-2 adrenoceptors as target for drug discovery.

The presynaptic terminal autoreceptors which modulate the release of noradrenaline through a negative feed-back mechanism correspond to the alpha 2-subtype of adrenoceptors. These receptors are also present post-synaptically in the pancreatic islets were they mediate inhibition of the glucose-induced release of insulin. The sympathetic innervation of the pancreatic islets involves alpha 2-adrenoceptors both presynaptically as well as postsynaptically. SL 84.0418 is a novel alpha 2-adrenoceptor antagonist with preferential effects in the periphery and with at least a 10-fold higher selectivity ratio between alpha 2 and alpha 1-adrenoceptors when compared with idazoxan. SL 84.0418 antagonizes the hyperglycemia and the inhibition of insulin release induced by the alpha 2-adrenoceptor agonist UK 14304. The administration of SL 84.0418 significantly reduces the glucose evoked hyperglycemia in several species including man. It is proposed that SL 84.0418 may represent a useful and novel hypoglycemic drug in the treatment of type II diabetes.

Adrenergic alpha-Agonists↗
PubMed2004

Nitric oxide synthase inhibition during synaptic maturation decreases synapsin I immunoreactivity in rat brain.

During the development of the brain, nitric oxide and synapsins, the latter being phosphoproteins associated to presynaptic membrane vesicles, are abundant in presynaptic terminals and play important and similar roles in neurotransmitter release, morphogenesis, synaptogenesis, and synaptic plasticity. These mechanisms are fundamental for neuronal development and plasticity and constitute important factors for the formation of neuroanatomical structures. Neural nitric oxide synthase (nNOS), synapsin I, and nNOS adapter protein (CAPON) constitute a ternary complex necessary for specific NO and synapsin functions at a presynaptic level. It is not known whether NO absence may affect the presence and/or activity of synapsins during brain development. To understand the role of NO in synaptogenesis, we studied the effects of NOS inhibition on synapsin I expression at a postnatal stage. Rat pups were treated with a competitive NOS antagonist, N-nitro-L-arginine methyl ester, from postnatal days 3 to 23. Control pups received exclusively an equivalent volume of saline solution. Histochemical and immunochemical techniques for NADPH-d and synapsin I, respectively, were carried out. NOS inhibition elicited a significant reduction in synapsin I immunoreactive density and NADPH-d activity in the brain in the analyzed areas-prefrontal cortex, hippocampus, and dorsal thalamus. These data show that the alterations originated by NO and synapsin deficiencies produce a diminution in synaptic density. Thus, functions that depend on the formation of synaptic connections such as learning and memory could be affected by NO deficiency.

Animals↗
PubMed2003

Modulation of foregut synaptic activity controls resorption of molting fluid during larval molts of the moth Manduca sexta.

We examined the role of the foregut in the resorption of molting fluid (MF) from the exuvial space during the last larval-larval molt of the moth Manduca sexta. In intermolt larvae, the activity of the foregut is characterized by robust peristaltic contractions. With the onset of the molt, MF is secreted into the exuvial space where it digests and weakens the old cuticle. The appearance of MF in the exuvial space is accompanied by a dramatic reduction in the amplitude of the foregut contractions. Foregut peristalsis returned about halfway through the molt, followed shortly by the appearance of MF in the gut. These observations suggested that larvae use their foreguts to remove MF from the exuvial space. Animals whose foreguts were surgically inactivated did not resorb their MF and most failed to successfully shed their old cuticles. The reduction in foregut motility at the onset of the molt was correlated with a sharp decline in the amplitude of the excitatory junctional potentials. With the onset of the molt there was also a decline in the number of presynaptic terminals on the foregut that loaded with the activity-dependent dye FM1-43. In the second half of the molt, the appearance of MF in the foregut and the return of foregut motility was correlated with an increase in FM1-43 loading. These data reveal that during a larval-larval molt, vesicle release and/or recycling of the presynaptic endings on the foregut muscles is modulated to assure the proper timing of MF resorption.

Animals↗
PubMed2001

Multiple G-protein-coupled receptors mediate presynaptic inhibition at single excitatory synapses in the rat visual cortex.

Modulation of excitatory synaptic transmission by agonists for several neurotransmitter receptors was investigated at intrinsic cortical synapses derived from single presynaptic neurons. Excitatory postsynaptic currents (EPSCs) were recorded from layer 5 pyramidal neurons in the rat visual cortex in response to minimal stimulation within the same layer. 5-hydroxytryptamine, adenosine, baclofen, carbachol and DCG-IV all suppressed EPSCs with an increase in paired-pulse ratio. These agonists reduced the frequency of miniature EPSCs without significantly affecting their amplitude distribution. These results suggest that glutamatergic excitatory transmission in the neocortex is under the control of presynaptic inhibition mediated by multiple neuromodulator receptors co-expressed in single presynaptic terminals.

Adenosine↗
PubMed2006

Expression and function of SNAP-25 as a universal SNARE component in GABAergic neurons.

Intracellular vesicular trafficking and membrane fusion are important processes for nervous system development and for the function of neural circuits. Synaptosomal-associated protein 25 kDa (SNAP-25) is a component of neural soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complexes that mediate the exocytotic release of neurotransmitters at chemical synapses. Previous results from mouse mutant models and pharmacological/neurotoxin blockades have demonstrated a critical role for SNAP-25-containing SNARE complexes in action potential (AP)-dependent release at cholinergic and glutamatergic synapses and for calcium-triggered catecholamine release from chromaffin cells. To examine whether SNAP-25 participates in the evoked release of other neurotransmitters, we investigated the expression and function of SNAP-25 in GABAergic terminals. Patch-clamp recordings in fetal Snap25-null mutant cortex demonstrated that ablation of SNAP-25 eliminated evoked GABA(A) receptor-mediated postsynaptic responses while leaving a low level of spontaneous AP-independent events intact, supporting the involvement of SNAP-25 in the regulated synaptic transmission of early developing GABAergic neurons. In hippocampal cell cultures of wild-type mice, punctate staining of SNAP-25 colocalized with both GABAergic and glutamatergic synaptic markers, whereas stimulus-evoked vesicular recycling was abolished at terminals of both transmitter phenotypes in Snap25-/- neurons. Moreover, immunohistochemistry and fluorescence in situ hybridization revealed coexpression of SNAP-25, VGAT (vesicular GABA transporter), and GAD65/67 (glutamic acid decarboxylase 65/67) in interneurons within several regions of the adult brain. Our results thus provide evidence that SNAP-25 is critical for evoked GABA release during development and is expressed in the presynaptic terminals of mature GABAergic neurons, consistent with its function as a component of a fundamental core SNARE complex required for stimulus-driven neurotransmission.

Animals↗
PubMed1995

Role of calcium channel subtypes in calcium transients in hippocampal CA3 neurons.

Multiple subtypes of voltage-gated calcium channels are differentially localized in brain neurons suggesting that they serve distinct roles in neuronal excitation and signaling. In organotypic hippocampal slice cultures, class D (L-type) calcium channels are predominantly located in the cell bodies of CA3 neurons while class B (N-type) and class A (P or Q-type) are localized in dendrites and associated presynaptic terminals with relatively low somal expression. Using specific antagonists to inhibit calcium transients recorded in CA3 neuronal cell bodies, we found that L-type calcium channels have a predominant role in somal calcium transients elicited by trains of strong stimuli applied to either the soma or the distal apical dendrite while class A calcium channels make a smaller contribution. Presynaptic class B (N-type) and class A (P- and/or Q-type) calcium channels are critical for glutamate-mediated synaptic transmission onto the dendrites of CA3 neurons. Postsynaptic class A and B calcium channels detected on the dendritic shaft by immunocytochemistry were not found to contribute substantially to somal calcium transients during repetitive stimulation of distal dendrites, but sodium channels were required for calcium transients elicited by somatic or dendritic stimulation. Our results show that the different calcium channel subtypes serve distinct roles in cellular activation and transmission of signals in CA3 neurons, consistent with their differential subcellular localization.

Animals↗