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At least 1,531 records · Page 85Linked to original sources
PubMed1996

Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries.

Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic receptors in rat cortical capillaries was approached by way of immunocytochemistry at the ultrastructural level using monoclonal antibody M35 against muscarinic receptor protein. Binding of this antibody in the microvascular domain was found in 5% of the capillaries studied and was exclusively present in perivascular astroglia, and never in endothelium or pericytes. Combined with reported data on presynaptic cholinergic innervation the results indicate a cholinergic innervation pattern of non-directed presynaptic terminal structures in apposition to cholinoceptive perivascular astroglia with muscarinic receptor positive endfeet embracing the capillary basement membrane. The possible functional significance of such a cholinergic vascular innervation pattern is discussed with respect to capillary dynamics and barrier function.

Acetylcholine↗
PubMed1996

Nerve growth factor induced modification of presynaptic elements in adult visual cortex in vivo.

Nerve growth factor (NGF) has been shown to play important roles in neuronal survival, growth and differentiation. Recently, we have found that intracortical infusion of NGF into adult cat visual cortex can recreate ocular dominance plasticity, suggesting that NGF is also involved in activity-dependent modification of synaptic connectivity in the adult brain. To further explore the mechanisms of NGF-induced plasticity in adult visual cortex, we studied two presynaptic markers: GAP-43 and synaptophysin. Immunocytochemical staining showed that NGF-treatment of adult visual cortex selectively increased the level of the phosphorylated form of GAP-43, while the total level of GAP-43 was not changed. These results demonstrate that NGF-treatment stimulates phosphorylation processes of GAP-43 in vivo. In addition, NGF-treatment of adult visual cortex increased the level of synaptophysin immunoreactivity. Since the phosphorylated form of GAP-43 is known to be enriched in the membrane skeleton of growth cones and of developing synapses, and the phosphorylation of GAP-43 has been linked with events that underlie synaptic plasticity, and since synaptophysin is a major component of presynaptic vesicles, our results suggest that NGF-treatment of adult visual cortex modulates presynaptic terminals, possibly by inducing axonal sprouting and formation of new synapses, and that these changes may play a role in the NGF-induced functional plasticity.

Animals↗
PubMed1988

Immunocytochemical localization of protein kinase C in developing brain tissue and in primary neuronal cultures.

Antisera to protein kinase C (PKC) have been used to examine the presence and distribution of the enzyme in developing cerebellar cortex of postnatal rat and in cultures of rat sympathetic ganglia. In the cerebellar cortex of 2-,4-, and 6-day old rats, immunostaining was observed in areas of early-forming presynaptic terminals and growth cones. No staining was evident in the cortical proliferative zone. Beginning at 10 days postnatal, nuclear staining, not apparent at earlier stages, was prominent in Purkinje cells. In neuronal cultures of dissociated rat sympathetic ganglia, PKC was immunolocalized in cell bodies and bundles of neuronal processes. Immunoreactivity was particularly striking in growth cones of extending neurites and in axonal varicosities. These results suggest a role for PKC in neuronal growth following cell proliferation and in synaptic function. The appearance of nuclear staining in later developmental stages suggests that the enzyme may be involved in the promotion and maintenance of the differentiated state of neurons.

Animals↗
PubMed1976

Dantrolene and the neuromuscular junction: evidence for intracellular calcium stores.

Dantrolene sodium (DaNa) markedly depressed the frequency of spontaneous miniature potentials at the frog neuromuscular junction. Its action is still observed at low [Ca2+]o and is little affected by temperature; its effect is not readily reversible. Theophylline antagonises the action of DaNa. DaNa prevents the stimulatory effect of the ionophore A23187 at 25 degrees C, but is ineffective in antagonising the action of X537A. DaNa and theophylline do not affect the functioning and integrity of mitochondria in vitro and it is suggested that DaNa acts at intracellular Ca2+ stores (other than the mitochondria) in the presynaptic terminals.

Animals↗
PubMed1976

Effect of decentralization and glucose withdrawal on the potassium-induced cAMP increase in the rabbit superior cervical ganglion.

The concentration of cAMP in the isolated rabbit superior cervical ganglion (SCG) increases when the tissue is exposed to high potassium media for short periods. The increase was found not to be affected by agents that are known to potentiate or to antagonize the postsynaptic effects of acetylcholine. Pretreatment of the rabbits with various sympaticolytic substances did not appear to affect the cAMP increase in the isolated SCG. It was found that the K+-induced cAMP synthesis occurred neither in ganglia which had been decentralized 3 days before isolation nor in intact ganglia preincubated in a glucose-free medium. Under both these conditions the effect of potassium declines with a time course which is characteristic for the degeneration of the presynaptic terminals. These terminals therefore, appear to be the most likely site for the cAMP increase.

Animals↗
PubMed1978

Effect of erabutoxin B on acetylcholine release and root potentials of the frog spinal cord.

Erabutoxin b (ETX), a sea snake neurotoxin with neuromuscular blocking properties, slightly reduced resting ACh release from the isolated fron spinal cord. ETX did not affect ACh release evoked by antidromic stimulation of ventral roots but reduced the ventral-dorsal root potential and prolonged the dorsal-ventral root potential. The latter effect was associated with a reduction in the orthodromically evoked ACh release. It is suggested that ETX did not affect the presynaptic terminals of the motor axon collaterals and that its effects occurred at postsynaptic sites.

Acetylcholine↗
PubMed1979

The action of verapamil on the rate of spontaneous release of transmitter at the frog neuromuscular junction.

Verapamil is known to reduce Ca2+ entry in a variety of cells. At 10(-5) M it produces a small reduction in MEPP frequency at the frog neuromuscular junction, whereas the rate of spontaneous release rises following treatment at a concentration of 10(-4) M. This latter effect is augmented by raising [Ca2+]0 to 9 mM or, more especially, by raising the temperature from 17 to 23 degrees C. It is argued that both these opposing effects are related to the action of verapamil in modifying [Ca2+]i at the presynaptic terminals and it is suggested that the drug can affect both inward Ca2+ flux (so reducing the steady-state position of [Ca2+]i) and also, at higher concentration, either inhibit the membrane Ca2+ pump or cause the release of Ca2+ from intracellular Ca2+ stores (so raising [Ca2+]i).

Action Potentials↗
PubMed1985

DMI, Wy-45,030, Wy-45,881 and ciramadol inhibit locus coeruleus neuronal activity.

Wy-45,030 and Wy-45,881 block the uptake of norepinephrine and serotonin in rat brain synaptosomal preparations and share several in vivo and in vitro effects with known tricyclic antidepressants. To further characterize their activity, these compounds were compared to desipramine and ciramadol in electrophysiological studies of their acute effects on noradrenergic neuronal activity. All four compounds inhibited locus coeruleus neuronal activity with a rank order of potency of desipramine greater than Wy-45,881 greater than Wy-45,030 greater than ciramadol. Administration of the alpha-adrenergic blocking drug, piperoxane, increased locus coeruleus firing rate after desipramine, Wy-45,030 and Wy-45-881. Pretreatment with naloxone prevented the reduction in locus coeruleus impulse flow observed after ciramadol administration but had no effect on the inhibition produced by Wy-45,030. Wy-45,030 and Wy-45,881, like classical antidepressants, appear to inhibit locus coeruleus neuronal firing by potentiating neuroinhibitory transmission of locus coeruleus neurons by blocking the uptake of norepinephrine into presynaptic terminals.

Animals↗
PubMed1989

Effects of cholinergic drugs on extracellular levels of acetylcholine and choline in rat cortex, hippocampus and striatum studied by brain dialysis.

A brain dialysis technique was used to investigate the effects of cholinergic drugs on acetylcholine (ACh) release and on the extracellular choline levels. Scopolamine (0.5 mg/kg s.c.) markedly increased ACh release in frontal cortex, hippocampus and corpus striatum. Conversely, it significantly decreased choline levels in extracellular spaces of these three regions. Oxotremorine (0.5 mg/kg i.p.) induced no significant ACh release in these three regions, probably due to the presence of highly concentrated physostigmine in the perfusate, while it induced an increase of the choline levels in both frontal cortex and hippocampus but not in corpus striatum. Nicotine (0.5 mg/kg s.c.) significantly increased the ACh release in these three regions with no change in choline levels. Nicotine had a biphasic effect on ACh release in frontal cortex and hippocampus but not in corpus striatum. It should be noted that all such cholinergic drugs, in our time course determinations, yielded certain differences among these brain regions for both the magnitude and the response pattern of ACh and choline levels. The present investigation appears to indicate that the in vivo brain dialysis technique can be useful for probing cholinergic neurotransmission of cholinergic drugs via presynaptic terminals.

Acetylcholine↗
PubMed1990

Electrophysiological effects of dopamine autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232.

The weak aminotetralin stimulants, (+)-AJ 76, cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin and (+)-UH 232, cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, were tested for their effects on firing rates of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNPC). (+)-AJ 76 and (+)-UH 232 antagonized the depression of DA neuron firing rates following autoreceptor stimulation by apomorphine. Thus, just as they antagonize DA autoreceptors on presynaptic terminals, these aminotetralins also antagonize the somatodendritic DA autoreceptor. However, in contrast to terminal autoreceptors where (+)-AJ 76 is the most potent antagonist, (+)-UH 232 is the most potent on cell body autoreceptors. (+)-AJ 76 and (+)-UH 232 also reversed the depression of DA neurons arising from activation of negative feedback pathways by amphetamine-induced DA release in postynaptic areas. Based on potencies to reverse amphetamine and apomorphine, respectively, the postsynaptic/presynaptic potency ratios for (+)-AJ 76, (+)-UH 232, and haloperidol were all near unity. It is concluded that (+)-AJ 76 and (+)-UH 232 antagonize both postsynaptic and somatodendritic sites with equal potencies, and that their weak stimulant properties may be due to a preferential antagonism of nerve terminal autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat.

GABAA and GABAB receptor agonists and antagonists were administered locally in the striatum of intact and kainic acid lesioned rats. (+/-)-Baclofen, a GABAB receptor agonist, significantly decreased the level of extracellular dopamine in the striatum of intact rats. (+/-)-Phaclofen, a GABAB receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats and to a lesser extent in the striatum after kainic acid lesion. Pregnanolone (5 beta-pregnan-3 alpha-ol-20-one), a positive allosteric modulator of the GABAA receptor, significantly decreased the level of extracellular dopamine in intact rats. (-)-Bicuculline, a GABAB receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats, but failed to increase the level of extracellular dopamine after kainic acid lesion. The release of extracellular dopamine, due to infusion of phaclofen or bicuculline, was totally suppressed by tetrodotoxin. These results support a direct influence of GABA on the dopaminergic terminals via presynaptic GABAB receptors, while the effects via the GABAA receptor seem to be postsynaptic and mediated by striatal interneurons or the striatonigral feedback loop.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

The vesicular monoamine transporter is not regulated by dopaminergic drug treatments.

The number of neuronal synaptic vesicular monoamine transporters (vesicular monoamine transporter type 2; VMAT2) has been recently proposed as an index of monoamine presynaptic terminal density. The present study investigated the possible regulation of the vesicular monoamine transporter. Rats were treated for 2 weeks with drugs known to influence dopaminergic neurotransmission, including those commonly used in the treatment of Parkinson's disease. Autoradiographic assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN 35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma membrane dopamine re-uptake site bindings, respectively. None of the drug treatments significantly modified levels of vesicular monoamine transporter binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites were altered by some of the treatment regimens. These data extend preliminary results that suggest the vesicular monoamine transporter is not easily regulated and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake site. Measures of striatal vesicular monoamine transporter density may, thus, provide objective estimates of monoaminergic innervation in neurodegenerative diseases, unaffected by the use of symptomatic therapies.

Animals↗
PubMed1996

Subcellular localization of ryanodine receptors in rat brain.

Subcellular fractions of rat brain were used to determine the subcellular localization of ryanodine receptors. [3H]Ryanodine binding in purified cortical, cerebellar and hippocampal synaptosomes was up to 3.6-fold higher compared with mitochondrial fractions. The density of sites (Bmax) in hippocampal mossy fiber synaptosomes (249 fmol/mg protein) was 3.7-fold greater than in cortical synaptosomes (67 fmol/mg protein) and binding affinity was approximately 2-fold greater in the former (KD, 6.1 nM) than the latter (KD, 3.1 nM). At single sub-saturating concentrations of [3H]ryanodine, binding was 1.6-fold higher in mossy fibers compared with total hippocampal synaptosomes. [3H]Ryanodine binding sites were distributed similarly in subfractions of cortical synaptosomes and microsomes from discontinuous sucrose density gradients. An enrichment of sites was found in the lightest fractions containing the lowest activities of plasma membrane (5'-nucleotidase) and endoplasmic reticulum (glucose 6-phosphatase) enzyme markers when data for microsomal and synaptosomal subfractions were expressed as activity/binding per mg protein and when data for synaptosomal subfractions were expressed as a percentage of total activity/binding in collected fractions. Thus, ryanodine receptors appear to be concentrated in presynaptic terminals where they may play a major role in neurotransmitter release, and appear to be localized either in a specialized endoplasmic reticulum subcompartment or a distinct subcellular organelle.

Animals↗
PubMed1996

Preferential enhancement of inhibitory synaptic transmission by CS-722 in the ventral horn neurons of neonatal rat spinal cord.

We studied the modulatory effect of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a centrally acting muscle relaxant, on synaptic transmission in the ventral horn neurons of neonatal rat lumbar spinal cord in slices using whole cell recording techniques. Pharmacologically isolated excitatory or inhibitory postsynaptic currents (EPSCs and IPSCs) were evoked by stimulating neighboring neurons. CS-722 preferentially enhanced IPSCs with little effects on EPSCs. Moreover, CS-722 reduced paired pulse facilitation of gamma-aminobutyric acid (GABA)-mediated IPSCs, suggesting its action on the presynaptic terminal. Preferential facilitatory effects on inhibitory synaptic transmission seem to be one of the mechanisms underlying muscle relaxation of this compound.

Animals↗
PubMed1988

Scanning electron microscopic study of the neuromuscular junction of dystrophic mice.

The structure of the end-plate regions of normal and dystrophic 3-month-old mice were studied by scanning electron microscopy after the presynaptic terminals were removed by hydrochloric acid treatment. Quantitative analysis revealed that the end-plate area correlated positively with the muscle fiber diameter in both the normal and dystrophic animals. However, the motor end-plate area was significantly smaller in the dystrophic mice. The total length of the primary cleft of an end-plate correlated positively with the end-plate area and with the muscle fiber diameter in both normal and dystrophic mice. However, the total length of the primary cleft of an end-plate was significantly shorter in dystrophic mice, especially in large-diameter muscle fibers. Finally, the end-plate of dystrophic mice was characterized by shorter primary clefts with less branching points. These changes of several morphometric characteristics of the postsynaptic membrane suggest that the functional denervation of the mouse dystrophic neuromuscular junction has a postsynaptic origin.

Animals↗
PubMed1992

Synaptic reorganization in the feline ventral anterior thalamic nucleus induced by lesions in the basal ganglia.

This report presents the results of quantitative analysis of synaptic coverage of the dendrites of thalamocortical projection neurons in the adult cat ventral anterior thalamic nucleus (VA) and its changes at short (4 days)- and long-term (1 year) survival times after combined unilateral kainic acid lesions in the substantia nigra pars reticularis and entopeduncular nucleus. The study showed that deafferentation induced an increase in the appositional length of the dendrites of GABAergic local circuit neurons along projection neuron dendrites, accompanied by an increase in the number of dendrodendritic synapses. Dendritic or axonic origin of other unusual presynaptic structures at 1 year postlesion could not be established with certainty. All of them displayed some features of growth cones, such as an abundance of tubular and vesicular structures many with electron-dense contents. Projection neuron dendrites postsynaptic to these profiles contained numerous coated vesicles at the same survival time. The findings suggest that (i) the lesioning of the two basal ganglia output structures induces synaptic reorganization in the VA, (ii) this process appears to be active at 1 year after deafferentation, and (iii) all reactive systems display symmetric contacts and positive GAD immunoreactivity suggesting that homotypic remodeling is taking place. Despite the signs of remodeling, the density of presynaptic terminals with symmetric contacts on primary and secondary projection neuron dendrites in the VA remained below the control level at 1 year postlesion suggesting that an imbalance of excitatory and inhibitory inputs on thalamocortical projection neurons may persist for long periods after deafferentation.

Animals↗
PubMed1986

Effects of [D-Ala6, Pro9-NEt]-LHRH and catecholaminergic drugs on gonadotropin secretion and ovulation in the Chinese loach (Paramisgurnus dabryanus).

The effects of [D-Ala6,Pro9-NEt]-LHRH (LHRH-A) alone and in combination with drugs which influence the actions of dopamine or the synthesis of catecholamines on gonadotropin (GtH) secretion and ovulation in the loach (Paramisgurnus dabryanus) were investigated. LHRH-A alone stimulated an increase in serum GtH levels in the loach, but was a relatively ineffective treatment for the induction of ovulation. Injection of the dopamine receptor antagonist pimozide caused a marked potentiation of the GtH-release response to LHRH-A, and combined injections of pimozide and LHRH-A were an effective treatment for the induction of ovulation. Reserpine, a drug which causes depletion of catecholamines from presynaptic terminals, also caused a marked potentiation of the GtH-release response to LHRH-A and combined treatment induced ovulation. Similarly, administration of alpha-methyl-para-tyrosine to block conversion of tyrosine to L-dopa, or carbidopa to block conversion of L-dopa to dopamine, potentiated the GtH-release response to LHRH-A and induced ovulation. In contrast, the use of diethyldithiocarbamate, to block conversion of dopamine to norepinephrine, failed to augment the action of LHRH-A on GtH release and ovulation. The present results provide further evidence to suggest that dopamine functions as a gonadotropin release-inhibitory factor in teleosts, and demonstrate that the use of drugs which block either the synthesis or the actions of dopamine potentiates the action of LHRH-A in teleosts.

Animals↗
PubMed1989

Electrophysiological changes in the fasciculus gracilis of the cat following chronic clioquinol administration.

Clioquinol was administered to cats for more than 200 days, in order to investigate the neural mechanisms underlying the sensory disturbances of subacute myelo-opticoneuropathy (SMON). Electrophysiological examination, carried out under urethane-chloralose anesthesia, revealed that there were 3 major abnormalities in the surface potentials of the nucleus gracilis evoked by sural nerve stimulation, i.e., a reduction in the peak-to-peak amplitude, prolongation of the N wave, and a reduction in P wave amplitude. The reduction in P-wave amplitude suggested suppression of presynaptic inhibition. This was confirmed by excitability tests of the presynaptic terminals of sural nerve fibers within the nucleus gracilis. Recordings of orthodromic volleys in the fasciculus gracilis, elicited by sural nerve stimulation, showed an increase in temporal dispersion. Increased temporal dispersion was also evident from recordings of antidromic volleys in the sural nerve. Peripheral axons of primary sensory neurons in the sural nerve and their terminals within the spinal cord showed no significant functional abnormalities in the chronic clioquinol cat. It is suggested that primary axons in the fasciculus gracilis near the nucleus gracilis are affected by chronic clioquinol administration.

Action Potentials↗