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PubMed1990

Selective alterations in presynaptic cytomatrix protein organization induced by calcium and other divalent cations that modulate exocytosis.

Rises in intracellular calcium cause several events of physiological significance, including the regulated release of neuronal transmitters. In this study, the effects of divalent cations on the structural organization of cytomatrix in presynaptic terminals was examined. [35S]Methionine-radiolabeled guinea pig retinal ganglion cell cytomatrix proteins were axonally transported [in slow component b (SCb) of axonal transport] to the neuron terminals in the superior colliculus. When the peak of radiolabeled cytomatrix proteins reached the terminals, synaptosomes containing the radiolabeled cytomatrix proteins were prepared. Approximately 40% of each SCb protein was soluble after hypoosmotic lysis of the radiolabeled synaptosomes in the presence of divalent cation chelators. Lysis of synaptosomes in the presence of calcium ions over a range of concentrations, however, caused a dramatic decrease in solubility of the presynaptic SCb proteins. The cytoplasmic effects may result from a calcium-dependent condensation of cytoplasm around presynaptic terminal membrane systems. There are two major presynaptic SCb proteins (at 60 and 35 kDa), that exhibited exceptional behavior: they remained as soluble in the presence of calcium as under control conditions, suggesting that they were relatively unaffected by the mechanism causing the decrease in SCb protein solubility. Also examined were the effects of other alkaline earth and transition metal divalent cations on the presynaptic SCb proteins.

Animals↗
PubMed1981

[Ultrastructural of the neurons and synaptic architectonics of the central nucleus of the inferior colliculi in the cat brain].

In the central nucleus of the cat's brain inferior colliculus, three classes of neurons were observed. 1. Large relay neurons were distinguished by the abundance of cytoplasmic organelles. A considerable part of their perikaryon was covered by presynaptic terminals. 2. Medium sized lucent neurons having small amount of organelles. 3. Dark cells of rare occurrence in the central nucleus, which according to the number of axo-somatic synapses may be placed between type I and II neurons. In the central nucleus four type of profiles containing synaptic vesicles were distinguished. Large polymorphic endings of specific afferent fibers (type I) and small neurons (type II) contained round synaptic vesicles, while type III irregular axon terminals contained flattened and polymorphic ones. Type I, II and III terminals always appeared to be presynaptic components of synapses. Type IV terminals were found to be rare and except the polymorphic synaptic vesicles contained profiles of endoplasmic reticulum, ribosomes, microtubules, that enables them to be attributed to dendrites. Type IV terminals may be either presynaptic, or postsynaptic components of synapses.

Animals↗
PubMed2001

[Calcium dependent forms of synaptic plasticity in cerebellar Purkinje cells].

Elevation of intracellular calcium concentration ([Ca(2+)](i)) induces several forms of long-term synaptic plasticity in cerebellar Purkinje cells (PCs). These include (1) long-term depression (LTD) at parallel fiber (PF) to PC synapses, (2) LTD at climbing fiber (CF) to PC synapses, (3) long-term potentiation (LTP) at synapses from inhibitory interneurons (rebound potentiation). The current knowledge about calcium dependency for these forms of synaptic plasticity is described in this chapter. (1) Induction of PF-LTD is dependent on elevation of [Ca(2+)](i), that derives from two distinct sources. One is through voltage-dependent calcium channel (VDCC). A CF stimulation leads to elevation of [Ca(2+)](i) due to activation of VDCCs. The other is from the internal calcium store. PFs stimulation activates metabotropic glutamate receptor subtype 1 (mGluR1). It leads to production of inositol-1,4,5-triphosphate (IP(3)) and diacylglycerol (DG) which cause calcium release from internal stores and activation of protein kinase C, respectively. The conjunctive activation of PF and CF inputs is necessary for PF-LTD. (2) LTD at CF to PC synapses (CF-LTD) is induced by the mechanisms similar to those involved in PF-LTD. CF-LTD requires elevation of [Ca(2+)](i) and activation of the mGluR1 to PKC cascade. (3) Rebound potentiation is induced by transient elevation of [Ca(2+)](i) due to activation of VDCCs or IP3-mediated calcium release from internal stores. Elevation of [Ca(2+)](i) activates calcium/ calmodulin-dependent protein kinase II and leads to persistent up-regulation of postsynaptic GABAA receptor function. At the three types of synapses described above, elevation of [Ca(2+)](i) also causes short-term depression of neurotransmitter release from presynaptic terminals. Recent studies demonstrate that transient elevation of [Ca(2+)](i) produces endocannabinoids in PCs that act retrogradely onto presynaptic terminals and suppress neurotransmitter release.

English Abstract↗
PubMed1981

Synaptic junctions in the cat spinal ganglion.

The cervical dorsal root ganglia (C5-C8) of the cat were examined in vivo with an electron microscope. Cell processes of unknown origin were observed to invade the area between the satellite cell sheaths and the ganglion cells, and their terminals were found to be in synaptic contact with the soma of the ganglion cells. Like chemical synapses, these synapses are numerous, containing small and round vesicles and mitochondria in the presynaptic terminals and the asymmetrical membrane thickening. The postsynaptic membrane was thicker than the presynaptic one. These presynaptic terminals were surrounded by the satellite cell sheaths. The present study strongly suggested the presence of at least a few chemical synapses, especially axosomatic synapses, in the cat spinal ganglion.

Animals↗
PubMed1990

Synaptic morphometry and synapse-to-neuron ratios in the superior colliculus of albino rats.

The superior colliculus of mammals is generally divided into seven layers on the basis of the distribution of myelinated fibers, which are densely packed in layers III, V, and VII but sparse in the other layers. The laminar distribution of afferents and efferents allows, in addition, for the distinction of a superficial visual zone (layers I-III) and a deeper multimodal and premotor zone (layers IV-VII). Collicular neurons, however, do not show a lamination pattern, but are rather homogeneously distributed with only gradual transitions (Albers et al.: J. Comp. Neurol. 274:357-370, '88). The present study analyses whether the distribution of collicular synapses is correlated with the laminar organization of collicular axons or rather with the more homogeneous distribution of collicular neurons. For this purpose, the size and density of synaptic terminals and contacts as well as synapse-to-neuron ratios were determined in all collicular layers of albino rats by means of quantitative analysis of electron microscopic pictures. The size of presynaptic terminals and contacts does not differ significantly between individual collicular layers. On average, presynaptic terminal diameter is 1,079 nm, and synaptic contact size 338 nm, while 23% of all contacts are of the symmetrical type with pleiomorphic vesicles. The average numerical synaptic density is 422 million per mm3. This value is significantly higher in layers I and II (on average 670 million per mm3) than in layers III-VII (on average 370 million per mm3). The synapse-to-neuron (S/N) ratios calculated show that collicular neurons have on average 6,120 synaptic contacts on their receptive surface. The S/N ratio is lowest in layer III (4,330), while this ratio is highest in layers I and VII (i.e., 8,970 and 8,560 respectively). Layer II has a significantly higher S/N ratio than layer III (i.e., 8,060 and 4,330, respectively). Our results show that the size of synaptic terminals and contacts is not correlated with the different connectivity patterns of the distinct collicular layers. However, the density of synapses as well as the synapse-to-neuron ratios show a certain degree of laminar differentiation. In particular the superficial visual zone appears to be inhomogeneous in this respect, since layers I and II have a significantly higher density of synapses and higher S/N ratios than layer III. The deeper collicular zone is more homogeneously organized with synaptic densities similar to that of layer III and gradually increasing synapse-to-neuron ratios from layer IV to layer VII.

Animals↗
PubMed2000

Ultrastructural localization of mint1 at synapses in mouse hippocampus.

Mint1 and mint2 were isolated in the course of seeking the protein ligands to munc18-1, a neuronal protein essential for synaptic vesicle exocytosis. The mint family of proteins has been highly conserved in the course of evolution, being retained from C. elegans to mammals. Several lines of biochemical and genetic evidence have suggested that mint1 and LIN-10, its homologue in C. elegans, function at synapses in the brain. Because the precise subcellular location of mint1 is incompletely known, we used immunostaining to examine the distribution of mint1 in the mouse brain including ultrastructural localization in synapses. Strong, finely punctate mint1 immunolabeling was detected throughout the brain, including cerebral cortex, striatum, hippocampus, thalamus, basal ganglia and cerebellum. At the most synapses in the molecular layer, mint1 was particularly abundant at the active zone and to a lesser extent in association with synaptic vesicles in the presynaptic terminals. In contrast, a very few synapses showed mint1 immunoreactivity in the postsynaptic density and there was no synapse double-positive in presynaptic and postsynaptic terminals. Mint1 distribution within presynaptic terminals overlapped that of munc18-1. These localization results are consistent with previously demonstrated biochemical interactions and strongly support functions of mint1 in synaptic vesicle exocytosis and synaptic organization in the central nervous system.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Long-term blockade of serotonin reuptake affects synaptotagmin phosphorylation in the hippocampus.

Synaptic vesicle trafficking and transmitter release from presynaptic terminals are precisely regulated by a complex array of protein/protein interactions. Several of these proteins are substrates of endogenous protein kinases present in presynaptic terminals. The activity of Ca2+/calmodulin-dependent protein kinase II(CaMKII), one of the kinases involved in the modulation of transmitter release, was previously shown to increase in the hippocampus after long-term blockade of 5-hydroxytryptamine (5-HT) reuptake (a treatment known to elicit an increase in 5-HT release in this area). To investigate the changes induced in presynaptic protein phosphorylation by 5-HT reuptake blockade and concomitant CaMKII up-regulation, we analyzed two major CaMKII presynaptic substrates (synapsin I and synaptotagmin). All 5-HT reuptake blockers that we used, which induce an increase in CaMKII activity and autophosphorylation, also caused a large (2-3-fold) increase in the Ca2+/calmodulin-dependent post hoc phosphorylation of synaptotagmin. Conversely, the phosphorylation of synapsin I is much less affected. The change in synaptotagmin phosphorylation, as determined through immunoprecipitation and quantitative immunoblot analysis after fluvoxamine treatment, is due exclusively to increased phosphate incorporation (presumably caused by the increased kinase activity) and not to a change in the level of substrate protein after the treatment. Thus, drugs known to induce an increase in 5-HT release simultaneously induce an increase in the activity of presynaptic CaMKII and in the phosphate incorporation (post hoc) by a major CaMKII substrate in synaptic vesicles (synaptotagmin). This finding establishes a link between the facilitation of transmitter release induced by antidepressant drugs and the phosphorylation of synaptotagmin by CaMKII.

Animals↗
PubMed1997

Molecular biology of glycinergic neurotransmission.

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem of vertebrates. Glycine is accumulated into synaptic vesicles by a proton-coupled transport system and released to the synaptic cleft after depolarization of the presynaptic terminal. The inhibitory action of glycine is mediated by pentameric glycine receptors (GlyR) that belong to the ligand-gated ion channel superfamily. The synaptic action of glycine is terminated by two sodium- and chloride-coupled transporters, GLYT1 and GLYT2, located in the glial plasma membrane and in the presynaptic terminals, respectively. Dysfunction of inhibitory glycinergic neurotransmission is associated with several forms of inherited mammalian myoclonus. In addition, glycine could participate in excitatory neurotransmission by modulating the activity of the NMDA subtype of glutamate receptor. In this article, we discuss recent progress in our understanding of the molecular mechanisms that underlie the physiology and pathology of glycinergic neurotransmission.

Amino Acid Transport Systems, Neutral↗
PubMed1999

An immunohistochemical study of Purkinje cells in a case of hereditary cerebellar cortical atrophy.

We report an immunohistochemical study of Purkinje cells located in the molecular layer (ectopic Purkinje cells) and in the Purkinje cell layer (orthotopic Purkinje cells) of a patient who died young and had been diagnosed with hereditary cerebellar cortical atrophy from both clinical and neuropathological findings. All the ectopic and orthotopic Purkinje cells were immunoreactive with an anti-calbindin-D antibody, confirming that these stained cells were Purkinje cells. The perikarya of some ectopic and orthotopic Purkinje cells were stained by an antibody to phosphorylated neurofilament. In contrast, Purkinje cells of three normal controls did not react with this antibody. This finding of an abnormal accumulation of phosphorylated neurofilaments in the perikarya may be due to abnormal phosphorylation. Moreover, the regions around the cell bodies of some ectopic and orthotopic Purkinje cells were intensely immunoreactive with an antibody to synaptophysin, which suggests an abnormal increase in presynaptic terminals. It is suggested that ectopia of Purkinje cells, accumulation of phosphorylated neurofilament in the perikarya and an abnormal increase in presynaptic terminals around the soma of the Purkinje cells may be relevant to the pathophysiology of Purkinje cell degeneration in this case. In addition, the relationship between phosphorylated neurofilament and synaptophysin reactivity is discussed.

Adult↗
PubMed2004

Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling.

The cholinergic system in the CNS plays important roles in higher brain functions, primarily through muscarinic acetylcholine receptors. At cellular levels, muscarinic activation produces various effects including modulation of synaptic transmission. Here we report that muscarinic activation suppresses hippocampal inhibitory transmission through two distinct mechanisms, namely a cannabinoid-dependent and cannabinoid-independent mechanism. We made paired whole-cell recordings from cultured hippocampal neurons of rats and mice, and monitored inhibitory postsynaptic currents (IPSCs). When cannabinoid receptor type 1 (CB1) was blocked, oxotremorine M (oxo-M), a muscarinic agonist, suppressed IPSCs in a subset of neuron pairs. This suppression was associated with an increase in paired-pulse ratio, blocked by the M(2)-preferring antagonist gallamine, and was totally absent in neuron pairs from M(2)-knockout mice. When CB1 receptors were not blocked, oxo-M suppressed IPSCs in a gallamine-resistant manner in cannabinoid-sensitive pairs. This suppression was associated with an increase in paired-pulse ratio, blocked by the CB1 antagonist AM281, and was completely eliminated in neuron pairs from M(1)/M(3)-compound-knockout mice. Our immunohistochemical examination showed that M(2) and CB1 receptors were present at inhibitory presynaptic terminals of mostly different origins. These results indicate that two distinct mechanisms mediate the muscarinic suppression. In a subset of synapses, activation of M(2) receptors at presynaptic terminals suppresses GABA release directly. In contrast, in a different subset of synapses, activation of M(1)/M(3) receptors causes endocannabinoid production and subsequent suppression of GABA release by activating presynaptic CB1 receptors. Thus, the muscarinic system can influence hippocampal functions by controlling different subsets of inhibitory synapses through the two distinct mechanisms.

Animals↗
PubMed1979

Inhibitory effects of cholinergic agents on the release of transmitter at the frog neuromuscular junction.

1. The cholinesterase inhibitors neostigmine, edrophonium and eserine (7 x 10(-7) M) reduced m.e.p.p. frequency by some 50% at the frog neuromuscular junction. Neostigmine also produced a small reduction in quantal content. 2. Tetraisopropylpyrophosphoramide, with a high specificity for non-specific cholinesterase, has a similar effect on m.e.p.p. frequency but ambenonium, with a high specificity for acetylcholinesterase, was markedly less effective in this respect. 3. Carbachol (10(-5) M) and the muscarinic agonists muscarine and metacholine (7 x 10(-7) M) also reduced the rate of spontaneous release. 4. The action of neostigmine was antagonized by atropine, but not by D-tubocurarine. Muscarine did not have any further effect when m.e.p.p. frequency was reduced with neostigmine. 5. Experiments with reduced extracellular Ca2+ concentration suggest that the cholinergic agents reduce Ca2+ permeability directly at the presynaptic terminals and that they do not act via a change in PNa or PK. It is suggested that the consequent reduction in Ca2+ entry causes a fall in both evoked release and in intracellular Ca2+ concentration, thereby reducing m.e.p.p. frequency. 6. It is concluded that non-specific cholinesterases present on the presynaptic terminals can act as inhibitory muscarinic cholinergic receptors. This form of presynaptic inhibition at the amphibian neuromuscular junction contrasts with that described in the mammalian preparation in which the sites are blocked by D-tubocurarine and are excitatory.

Acetylcholine↗
PubMed1993

Preferential inhibition of omega-conotoxin-sensitive presynaptic Ca2+ channels by adenosine autoreceptors.

Adenosine is a potent modulator of transmitter release at a variety of synapses. The adenosine A1 receptor is assumed to reside in presynaptic terminals and to function as a negative autoreceptor. How adenosine reduces transmitter release is uncertain; it may reduce the calcium influx during nerve terminal depolarization by either activating K+ currents or inhibiting Ca2+ currents, although other mechanisms have been proposed. We have directly measured intracellular Ca2+ concentrations of giant pre-synaptic terminals in the chick ciliary ganglion. We report here that adenosine inhibited the nerve-evoked Ca2+ influx in the terminal by activating A1 receptors. Reduced Ca2+ influx was due largely to inhibition of omega-conotoxin GVIA-sensitive Ca2+ channels in the presynaptic terminal.

Adenosine↗
PubMed1985

Cytochemical analysis of oligosaccharide processing in frog photoreceptors.

Lectin cytochemistry, together with exoglycosidase enzyme digestion, has been used to characterize partially glycoconjugates of several intracellular compartments in frog photoreceptors. In order to obtain uniform access of reagents to all intracellular compartments, the experiments were performed directly on semi-thin sections of Xenopus laevis retinal tissue embedded in a hydrophilic plastic resin. In the rod, the major photoreceptor intracellular binding sites for wheat germ agglutinin (WGA) are the outer segment, the Golgi complex, and other inner segment organelles which are probably involved in the transport of glycoconjugates from the Golgi complex to the outer segment. In addition, shed outer segment tips (phagosomes) are uniformly labelled with WGA. The WGA-binding sites of the outer segment and of the presumed transport organelles are resistant to neuraminidase digestion. This is consistent with the possibility that glycoconjugates (primarily opsin) are transported from the Golgi complex to the outer segment without further oligosaccharide processing. Specific staining of rod outer segments and of phagosomes is also obtained with the N-acetylglucosamine-specific lectin, succinyl-WGA (S-WGA). Outer segments and phagosomes stain the same with WGA, S-WGA and a variety of other lectins tested suggesting that no major post-Golgi oligosaccharide processing accompanies the shedding-phagocytosis event. Concanavalin A (Con A) staining of intracellular sites in rod inner segments reveals a striking difference compared to WGA staining in that the Con A binding sites are concentrated in the photoreceptor axon and presynaptic terminal. These results, and results from previous studies, indicate that the photoreceptor may utilize different mechanisms of oligosaccharide processing from the level of a single Golgi complex to the opposite ends of this cell. Furthermore, those glycoconjugates destined for the presynaptic terminal may undergo post-Golgi processing at or near their sites of insertion into the presynaptic plasma membrane.

Animals↗
PubMed2003

Opioid receptor activation attenuates nicotinic enhancement of spontaneous GABA release in lateral spiriform nucleus of the chick.

We examined the effects of opioids on the nicotinic enhancement of spontaneous GABA release from presynaptic terminals in the lateral spiriform nucleus (SpL) of the chick. Whole cell recordings from SpL neurons in brain slices were used to monitor spontaneous GABA release. Nicotine (1 microM) produced an 8-fold increase in the frequency of GABA events without changing their amplitude, consistent with an increase of GABA release from presynaptic terminals. L-enkephalin (1 microM) blocked these effects of nicotine on presynaptic GABA release, and the opioid antagonist naloxone (100 nM) antagonized the actions of L-enkephalin. The selective mu agonist DAMGO (300 nM) also attenuated the nicotine-mediated enhancement of GABA release, and the mu selective antagonist CTOP (1 microM) blocked the actions of DAMGO. In contrast, the kappa opioid agonist U50488 (3 microM) and the delta opioid agonist DPDPE (1 microM) had no effect. The results demonstrate that presynaptic release of GABA in the SpL can be regulated by both nicotinic agonists and mu opioids. While mu opioids have little effect on GABA release by themselves, they are able to block the marked enhancement of GABA release normally produced by nicotine. Since both cholinergic and enkephalinergic nerves are present in the SpL, the interactions of these two neurotransmitter systems may serve to precisely regulate GABA release in this brain region.

Animals↗
PubMed1991

Noradrenaline release from streptolysin O-permeated rat cortical synaptosomes: effects of calcium, phorbol esters, protein kinase inhibitors, and antibodies to the neuron-specific protein kinase C substrate B-50 (GAP-43).

We studied the molecular mechanism of noradrenaline release from the presynaptic terminal and the involvement of the protein kinase C substrate B-50 (GAP-43) in this process. To gain access to the interior of the presynaptic terminal, we searched for conditions to permeate rat brain synaptosomes by the bacterial toxin streptolysin O. A crude synaptosomal/mitochondrial preparation was preloaded with [3H]noradrenaline. After permeation with 0.8 IU/ml streptolysin O, noradrenaline efflux could be induced in a concentration-dependent manner by elevating the free Ca2+ concentration from 10(-8) to 10(-5) M. Efflux of the cytosolic marker protein lactate dehydrogenase was not affected by this increase in Ca2+. Ca2(+)-induced efflux of noradrenaline was largely dependent on the presence of exogenous ATP. Changing the Na+/K+ ratio in the buffer did not affect Ca2(+)-induced noradrenaline release. Release of noradrenaline could also be evoked by phorbol esters, indicating the involvement of protein kinase C. Ca2(+)- and phorbol ester-induced release were not additive at higher phorbol ester concentrations (greater than 10(-7) M). We compared the sensitivities of Ca2(+)- and phorbol ester-induced release of noradrenaline to the protein kinase inhibitors H-7 and polymyxin B and to antibodies raised against synaptic protein kinase C substrate B-50. Ca2(+)-induced release was inhibited by B-50 antibodies and polymyxin B, but not by H-7; phorbol ester-induced release was inhibited by polymyxin B and by H-7, but only marginally by antibodies to B-50.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Differential expression of synapsins I and II among rat retinal synapses.

The synapsins are a family of synaptic vesicle-associated phosphoproteins thought to regulate the availability of vesicles for neurotransmitter release. In order to assess variability of synapsin isoform expression, we compared the localization of synapsins Ia, Ib, IIa, and IIb in the inner plexiform layer of the rat retina. Double labeling in conjunction with confocal fluorescence and electron microscopy allowed imaging of synapsin I and II immunoreactivity within single presynaptic terminals. No qualitative differences were observed between expression of the a and b isoforms of synapsin I in individual terminals; likewise, the a and b isoforms of synapsin II were identically distributed. In contrast, marked differences were seen upon comparison of synapsin I and synapsin II expression in single terminals. Our results indicate the existence of three classes of presumed amacrine cell synaptic terminals: synapsin I+/synapsin II-, synapsin I-/synapsin II+, and synapsin I+/synapsin II+. Each class of synapse has a different distribution among five IPL sublayers, suggesting that they represent different subpopulations of amacrine cells. Double labeling with an antibody to choline acetyltransferase indicates that synapsin I-/II+ terminals may be those of cholinergic amacrine cells. Furthermore, all synapsin II+ terminals appear to be distinct from those expressing the GABA synthetic enzyme glutamic acid decarboxylase. The observed variations in synapsin content suggest the existence of presynaptic terminal heterogeneity that is not apparent from conventional morphological studies.

Animals↗
PubMed2001

Adenosine A1 receptors reduce release from excitatory but not inhibitory synaptic inputs onto lateral horn neurons.

Although adenosine is an important neuromodulator in the CNS, its role in modulating sympathetic outflow at the level of the spinal cord has not been studied. Because very little is known about adenosine A1 receptors (A1Rs) in the spinal cord, we determined their location and role with particular reference to the control of sympathetic preganglionic activity and interneuronal activity in the rat. High levels of immunoreactivity for A1Rs were observed throughout the spinal cord. Immunostaining was dense in the intermediolateral cell column (IML) and intercalated nucleus, regions containing retrogradely labeled sympathetic preganglionic neurons (SPNs). Electron microscopy revealed A1R immunoreactivity (A1R-IR) within presynaptic terminals and (to a lesser extent) postsynaptic structures in the IML, as well as the luminal membrane of endothelial cells lining capillaries. Using double-labeling techniques, some presynaptic terminals were observed to synapse onto SPNs. To investigate the effects of activating these A1Rs, visualized whole-cell patch-clamp recordings were made from electrophysiologically and morphologically identified SPNs and interneurons. Applications of the A1R agonist cyclopentyladenosine (CPA) reduced the amplitude of EPSPs elicited by stimulation of the lateral funiculus, an effect blocked by the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine. These effects were attributable to adenosine acting at a presynaptic site because CPA application increased the paired-pulse ratio. CPA did not affect evoked IPSPs. These data show that activating A1Rs reduces fast excitatory, but not inhibitory, transmission onto SPNs and interneurons in the IML and that A1Rs may play a protective role on neurons involved in the control of sympathetic outflow.

Adenosine↗
PubMed1994

Ontogenetic effects of EEDQ on amphetamine-induced behaviors of rats: role of presynaptic processes.

Previous research has shown that the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) affects dopamine (DA) synthesis and metabolism in both preweanling and adult rats. In the present study, we attempted to determine the behavioral relevance of EEDQ's presynaptic actions. To that end, 17- and 90-day-old rats were injected with either EEDQ (7.5 mg/kg, IP) or its vehicle 30 min after half the rats were pretreated with the selective DA antagonists SCH 23390 and sulpiride. (SCH 23390/sulpiride pretreatment was used to protect D1 and D2 receptors from EEDQ-induced inactivation.) The behavioral effects of amphetamine (0, 0.1, 0.3 or 1.0 mg/kg, IP) were then assessed 1, 2, 4, and 8 days after EEDQ treatment. Amphetamine-induced behaviors were used to assess EEDQ's presynaptic actions, because amphetamine does not directly bind to the DA receptor, but rather releases DA from the presynaptic terminal. Further, since half of the EEDQ-treated rats had a full complement of DA receptors (i.e., those rats pretreated with SCH 23390/sulpiride), EEDQ's actions in the presynaptic terminal could be dissociated from actions at pre- and postsynaptic receptors. In general, the results showed that EEDQ blocked most of the amphetamine-induced behaviors of both 17- and 90-day-old rats. Surprisingly, pretreatment with SCH 23390 and sulpiride only protected the amphetamine-induced behaviors of adult rats, but not the behaviors of 17-day-old rat pups. When considered together, these results suggest that EEDQ's presynaptic effects are not behaviorally relevant to the adult rat, but may be responsible for eliminating amphetamine-induced behaviors in the 17-day-old rat pup.

Aging↗