bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calmodulin stimulates the degradation of brain spectrin by calpain
Authors: Seubert P. , Baudry M. , Dudek S. , Lynch G. 
Published: December 2004

AbstractBrain spectrin has been shown to be a preferential substrate of calciumdependent proteases (Baudry, Bundman, Smith, and Lynch: Science 212:937–938, 1981) and a major calmodulin‐binding protein (Kakiuchi, Sobue, and Fujita: FEBS Lett. 132:144–148, 1981). Since calmodulin, spectrin, and a proteolytically derived spectrin fragment are all components of isolated postsynaptic density preparations (Grab, Berzins, Cohen, and Siekevitz: J. Biol. Chem. 254:8690–8696, 1979; Carlin, Bartelt, and Siekevitz: J. Cell Biol. 96:443–448, 1983), we investigated the functional role of calmodulin binding to brain spectrin with respect to its susceptibility to digestion by proteases. We report that calmodulin's interaction with brain spectrin results in a marked acceleration of the rate of spectrin degradation by calcium‐dependent proteases (calpains I and II), but not by chymotrypsin. The cleavage of erythrocyte spectrin (which lacks a high‐affinity calmodulin binding site) by calpain I is unaffected by the presence of calmodulin. The stimulatory effect of calmodulin is blocked by trifluoperazine, a calmodulin antagonist, which by itself does not modify brain spectrin proteolysis by calcium‐dependent proteases. These results suggest a novel role for calmodulin in neuronal function—namely, a synergistic interaction with calcium‐dependent proteases in the regulation of cytoskeletal integrity.
Localization of neuropeptide Y messenger ribonucleic acid in rat and mouse brian by in situ hybridization
Authors: Gehlert D. R. , Chronwall B. M. , Schafer M. P. , O'Donohue T. L. 
Published: December 2004

AbstractThe distribution of neuropeptide Y (NPY) messenger ribonucleic acid (mRNA) in the rat and mouse brain has been examined. A 28‐mer oligonucleotide probe complementary to a distinctive region of NPY mRNA was 3′‐end labeled with [35S]‐deoxycytosine triphosphate ([35S]‐dCTP) by using terminal transferase and was hybridized to fixed sections of rat and mouse brain. The hybridization of the labeled probe to the mRNA in the tissue section was then detected autoradiographically. A strong hybridization signal was seen corresponding to the arcuate nucleus of the hypothalamus. Scattered NPY‐mRNA‐containing cell bodies were seen throughout the cerebral cortex. Experiments which compared the distribution of NPY mRNA with immunohistochemically detected NPY indicated a similar distribution in the arcuate nucleus of the hypothalamus and cerebral cortex. These results indicate that active transcription of the NPY gene occurs within the brain and this transcription takes place in NPY‐containing cell bodies.
An endogenous ligand for the sigma opioid binding site
Authors: Contreras Patricia C. , Dimaggio Debora A. , O'Donohue Thomas L. 
Published: December 2004

AbstractIt had been suggested that phencyclidine (PCP) and sigma opioids exert their similar psychotomimetic effects through a common receptor. Recently, however, there have been several reports demonstratin significant differences between the binding of PCP and SKF 10,047, a sigma opioid agonist, which suggests that there may be distinct PCP and sigma opioid receptors. If these differences in binding represent different receptors, then there may be different endogenous ligands for each receptor. Using porcine brains, which have already been used to isolate and purify an endogenous ligand for the PCP receptor, another factor has been isolated that inhibited the binding of [3H]‐(+)SKF 10,047 and not the binding of [3H]‐PCP. This factor appears to be a peptide or protein because incubation of the active fraction with pronase, a nonspecific peptidase, eliminated the ability of the procine fractions to inhibit the binding of [3H]‐(+)SKF 10,047. These findings suggest the existence of an endogenous ligand for sigma opioid receptors, which is different from the previously identified endogenous ligand for PCP receptors.
A critical level of protein synthesis is required for long‐term potentiation
Authors: Deadwyler Sam A. , Dunwiddie Tom , Lynch Gary 
Published: December 2004

AbstractLong‐term potentiation (LTP) of the hippocampal population spike in area CA1 was studied in the hippocampal slice before, during, and after inhibition of protein synthesis. LTP was tested 15 and 30 min following addition of the protein synthesis inhibitor cycloheximide (CXM) to the bathing medium. Stimulation‐induced LTP of the population spike was reduced in slices incubated in CXM for 15 min and completely blocked if incubated for 30 min. Measures of protein synthesis inhibition under the same conditions showed 79% at 15 min and 85% after 30 min. Tests of the effects of repeated LTP treatments at these same time points in the absence of CXM and evaluation of the time course of recovery of LTP from CXM blockade were also conducted. The results confirm previous observations and indicate that a critical amount of protein synthesis inhibition is required to completely block LTP in the hippocampal slice.
Differential effects of selective lesions of cholinergic and dopamingergic neurons on serotonin‐type 1 receptors in rat brain
Authors: Quirion Réami , Richard Jean 
Published: December 2004

AbstractSerotonin (5‐HT)‐type1 (abbreviated as a subscript 1) receptor binding sites are discretely distributed in rat brain. High densities of [3H]5‐HT1 binding sites are especially located in areas enriched with cholinergic and dopaminergic innervation, such as the substantia innominata/ventral pallidum, striatum, septal nuclei, hippocampus and substantia nigra. The possible association of [3H]5‐HT1 binding sites with cholinergic or dopminergic cell bodies and/or nerve fiber terminals was investigated by selective lesions of the substantia innominata/ventral pallidum‐cortical and septohippocampal cholinergic pathways and the nigrostriatal dopaminergic projection. [3H]5‐HT1 receptor binding sites are possibly located on cholinergic cell bodies in the ventral pallidum‐cortical pathway since [3H]5‐HT1 binding in the substantia innominata/ventral pallidal area was markedly decreased following kainic acid lesions. Fimbriaectomies markedly decreased [3H]5‐HT1 binding in the hippocampus, suggesting the presence of 5‐HT1 binding sites on cholinergic nerve fiber terminals in the septohippocampal pathway. Lesions of the nigrostriatal dopaminergic projection did not modify [3H]5‐HT1 binding in the substantia nigra and the striatum, suggesting that 5‐HT1 receptors are not closely associated with dopaminergic cell bodies and nerve terminals in this pathway. These results demonstrate differential association between 5‐HT1 receptors and cholinergic and dopaminergic innervation in rat brain.
Epinephrine and norepinephrine modulate neuronal responses to excitatory amino acids and agonists in frog spinal cord
Authors: Wohlberg C. J. , Hackman J. C. , Davidoff R. A. 
Published: December 2004

AbstractThe interaction of catecholamines epinephrine (E) and norepinephrine (NE) (1.0–100 μM) and excitatory amino acids on motoneurons of the isolated superfused frog spinal cord was investigated by sucrose gap recordings from ventral roots. Exposure of the cord to E or NE 30 sec prior to application of L‐aspartate or L‐glutamate reduced the motoneuron depolarizations produced by the amino acids. The reduction of responses to the mixed receptor agonists L‐glutamate and L‐aspartate may be the result of opposite actions of the catecholamines on the activation of specific excitatory receptors by the amino acids. Thus, E and NE facilitated depolarizations caused by application of N‐methyl‐D‐aspartate (NMDA) and depressed those produced by quisqualate. The effect on NMDA responses appeared to ne β‐adrenoceptor mediated because it was mimicked by the β‐agonist isoprotereno and blocked by propranolol. The effect on quisqualate depolarizations appeared to require activation of α2‐adrenoceptors; it was mimicked by the α2‐agonists clonidine and α‐methylnorepinephrine and antagonized by yohimbine and piperoxan. These results are important in understanding the actions of catecholamines on reflex transmission in spinal pathways which use excitatory amino acids as transmitters.
Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT1A receptors without altering 5‐HT autoreceptor sensitivity: An electrophysiological study in the rat brain
Authors: Blier Pierre , De Montigny Claude , Tardif Danielle 
Published: December 2004

AbstractShort‐term lithium administration to rats has previously been shown to enhance 5‐HT neurotransmission through a modification of 5‐HT neuron properties. In the first part of the present study, the effect of lithium on the function of terminal 5‐HT autoreceptors was assessed by comparing in controls and lithium‐treated rats the differential effect of two frequencies of stimulation (0.8 and 5 Hz) and that of methiothepin, a terminal 5‐HT autoreceptor antagonist, on the effectiveness of the electrical activation of the ascending 5‐HT pathway in suppressing dorsal hippocampus pyramidal neuron firing activity. Both procedures produced similar effects in controls and lithium‐treated rats. In the second part of the study, the function of somatodendritic 5‐HT autoreceptors was studied. The effect of intravenous LSD, an agonist of the somatodendritic 5‐HT autoreceptor, on the firing activity of 5‐HT neurons was not modified by the lithium treatment, whereas that of intravenous 8‐OH‐DPAT, a 5‐HT1A receptor agonist, was increased two‐fold. However, lithium did not alter the responsiveness of 5‐HT neurons to direct microiontophoretic applications of 8‐OH‐DPAT as well as of LSD and 5‐HT. It is concluded that short‐term lithium treatment does not alter the function of terminal and somatodendritic 5‐HT autoreceptors and that it enhances the sensitivity of subset of postsynaptic 5‐HT1A receptors involved in controlling 5‐HT neuron firing activity, presumably through a feedback loop.
Noradrenergic denervation prevents sensitization of rat forebrain neurons to serotonin by tricyclic antidepressant treatment
Authors: Gravel Pauline , De Montigny Claude 
Published: December 2004

AbstractThe effect of prior lesioning of noradrenergic neurons with 6‐hydroxydopamine (6‐OHDA) on the ability of amitriptyline to enhance the responsiveness of hippocampal pyramidal neurons to serotonin (5‐HT) was examined in Sprague‐Dawley rats. In control rats, amitriptyline (5 mg/kg/day for 14 days), administered either by daily injection or by an osmotic minipump, enhanced the responsiveness of these neurons to microionto‐phoretically applied 5‐HT, leaving their responsiveness to norepinephrine (NE) and to acetylcholine unaltered. However, in 6‐OHDA‐pretreated rats, amitriptyline failed to enhance the responsiveness of hippocampal pyramidal neurons to 5‐HT. The effect of NE and, to a lesser extent, that of 5‐HT were prolonged in 6‐OHDA‐pretreated rats, presumably because NE and 5‐HT released by microiontophoresis are taken up by NE terminals in the intact rat. The present results provide additional evidence that the integrity of the NE system is required for antidepressant treatments to modify 5‐HT neurotransmission.
Characterization and autoradiographic distribution of hemicholinium‐3 high‐affinity choline uptake sites in mammalian brain
Authors: Quirion Rémi 
Published: December 2004

Abstract[3H]hemicholinium‐3 (HC‐3) binding characteristics have been investigated using membrane binding assays and in vitro receptor autoradiography. In rat brain membrane preparations, [3H]HC‐3 binds with high affinity to an apparent single class of sites. [3H]HC‐3 selectivity labels the high affinity choline uptake (HACU) in brain membranes (HC‐3 > choline > carbamylcholine > acetylcholine). This hypothesis is also supported by quantitative autoradiographic data which demonstrate that the discrete distribution of [3H]HC‐3 binding sites correlates very well with the known distribution of other cholinergic markers such as choline acetyltransferase (ChAT), acetylcholinesterase (AChE), HACU, and [3H]AH‐5183 (blocker of the vesicular transport of acetylcholine). For example, high densities of labelling are observed for these different markers in the interpeduncular nucleus, anteroventral nucleus of the thalamus, striatum, basolateral nucleus of the amygdala, and an exquisite laminar distribution in the hippocampus. Similar autoradiographic distributions of [3H]HC‐3 binding sites are observed in other mammalian species such as guinea pig and monkey. Finally, 7‐day unilateral kainic acid lesions of the nucleus basalis magnocellularis (nbm) decrease cortical [3H]HC‐3 binding and ChAT activity, although not to a similar extent. In summary, these results demonstrate that [3H]HC‐3 is a selective ligand of the HACU in mammalian brain. Thus, it is now possible to characterize precisely various structural components of the cholinergic synapses using markers such as [3H]HC‐3, ChAT, HACU, [3H]AH‐5183, and selective muscarinic and nicotinic receptor radioligands.
Changes in synaptic morphology associated with presynaptic and postsynaptic activity: An in vitro study of the electrosensory organ of the thornback ray
Authors: Fields R. Douglas , Ellisman Mark H. , Waxman Stephen G. 
Published: December 2004

AbstractThe influence of synaptic activity on synaptic structure was studied by selectively stimulating the presynaptic or postsynaptic membranes of ribbon synapses in an in vitro preparation, and examining the ultrastructure of synapses with conventional electron microscopic methods. Functionally significant changes in synaptic morphology were observed after direct depolarization of the presynaptic membrane or incubation with the neurotransmitter glutamate to depolarize the postsynaptic membrane. After depolarizing the presynaptic membrane for 30 seconds, the depth of the postsynaptic trough was reduced, and other morphological changes correlated with decreased sensitivity and spontaneous activity were evident. Depolarizing the postsynaptic membrane by incubating synapses with the neurotransmitter glutamate, produced opposite effects. These results suggest that synapses can undergo functionally significant morphological changes in response to certain patterns of activity. The mechanism for these changes might include synaptic vesicle recycling processes, changes in ion concentration, or cytoskeletal alterations in the presynaptic, postsynaptic, or support cells. These mechanisms could operate in association with long‐term changes in synaptic efficacy or account for some physiological phenomena such as synaptic fatigue or accommodation.
Review: D1 dopamine receptor—the search for a function: A critical evaluation of the D1/D2 dopamine receptor classification and its functional implications
Authors: Clark David , White Francis J. 
Published: December 2004

AbstractThe present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase activity. The pharmacological effects of compounds exhibiting putative selective agonist or antagonist profiles at those DA receptors positively coupled to adenylate cyclase activity (D1 DA receptors) are extensively reviewed. Comparisons are made with the effects of putative selective D2 DA receptor agonists and antagonists, and on the basis of this work, the DA receptor classification is critically evaluated. A variety of biochemical, behavioral, and electrophysiological evidence is presented which supports the view that D1 and D2 DA receptors can interact in both an opposing and synergistic fashion. Particular attention is focused on the possibility that D1 receptor stimulation is required to enable the expression of certain D2 receptor‐mediated effects, and the functional consequences of this form of interaction are considered. A hypothetical model is presented which considers how both the opposing and enabling forms of interaction between D1 and D2 DA receptos can control behavioral expression. Finally, the clinical relevance of this work is discussed and the potential use of selective D1 receptor agonists and antagonists in the treatment of psychotic states and Parkinson's disease is considered.
Actions of serotonin recorded intracellularly in rat dorsal lateral septal neurons
Authors: Joëls M. , Gallagher J. P. 
Published: December 2004

AbstractThe actions of serotonin (5HT) on passive and active membrane properties of neurons in the rat dorsal lateral septal nucleus (LSN) were studied by using intracellular recordings in transverse, septal slices. Superfusion with 10 μm 5HT induced a hyperpolarization of the membrane in almost all neurons tested in the dorsolateral part of the LSN. The hyperpolarization was accompanied by a decrease in membrane resistance. These effects of 5HT persisted in a low‐Ca2+/high‐Mg2+‐containing medium or medium with tetrodotoxin, indicating a post‐synaptic site of action for 5HT. The reversal potential for the hyperpolarizing effect was ca. ‐95 mV. If the extracellular K+‐concentration was raised, the reversal potential became less negative. These data suggest that 5HT hyperpolarizes LSN neurons by increasing a K+‐conductance.Spontaneous, synaptically evoked action potentials and action potentials induced in LSN neurons by a depolarizing current step typically display a fast Na+‐spike with a subsequent K+‐afterhyperpolarization, followed by a much slower Ca2+‐dependent afterdepolarization. The amplitude of the K+‐afterhyperpolarization was decreased by 5HT, while at the same time the afterdepolarization became more pronounced. The Ca2+‐spike of LSN neurons was not affected by 5HT.Synaptic responses that were evoked in LSN neurons by stimulation of the dorsal part of the LSN consisted of a fast EPSP or spike, followed by a Cl−−‐dependent fast IPSP and a K+‐dependent late IPSP. Of these synaptic responses, 5HT suppressed particularly the late IPSP. The present data indicate that 5HT affects the conductance for active and passive K+‐channels in LSN neurons. While the increased conductance for passive K+‐channels directly hyperpolarizes and inhibits LSN neurons, the 5HT‐evoked changes in the shape of the action potential and IPSPs could facilitate transmission of excitatory signals in the LSN.
Serial reconstructions of granule cell spines in the mammalian olfactory bulb
Authors: Woolf Thomas B. , Shepherd Gordon M. , Greer Charles A. 
Published: December 2004

AbstractThe Morphology of olfactory bulb granule cell spines and their dendrodendritic synaptic relations with mitral and tufted cell dendrites were examined using serial electron micrographs and 3D computer reconstructions. Most granule cell spines were pedunculated with large elliptical heads necks (stems) longer than those described for exclusively postsynaptic spines elsewhere in the nerous system. The spines typically contained a mitochondrion, which most likely reflects the metabolic requirements of the presynaptic functions of these spines. In several cases multiple spine heads were observed connected to the parent dendritic trunk via a common neck. In addition, dendritic varicosities making synaptic connections were noted. In the data set sampled, all of the reconstructions supported the hypothesis of divergence of granule cell conectivity: in no instance was granule cell found to contact repeatedly the same mitral or tufted cell dendrite. Examination of the toplogical organization of reciprocal dendrodendritic synaptic connections with mitral/tufted cell dendrites revealed paralled rows of spine heads on mitral/tufted secondary dendrites separted by intervening zones of several microns in which no synaptic appositions were found. The results provide evidence regarding rules of connectivity underlying the function of local circuits in mediating lateral inhibition in the external plexiform layer of the olfactory bulb.
MK‐801 inhibition of nicotinic acetylcholine receptor channels
Authors: Amador Mariano , Dani John A. 
Published: December 2004

AbstractMK‐801 is a potent inhibitor of the NMDA subtype of glutamate receptors. Single‐channel and macroscopic current indicate that MK‐801 also inhibits nicotinic acetylcholine receptors (nAChRs). MK‐801 does not significantly increase desensitization of the nAChR, the main action of MK‐801 is to enter and block the open channel. The voltage dependence for block is consistent with a single binding site within the channel that is 50% of the way through the membrane field. The IC50 for block is 3 μM at‐70 mV for currents induced by 0.5 μ;M ACh. The data from both single‐channel and macroscopic currents can be used to estimate a Kd (0) of 7 μM, which is about 40 times higher than the Kd(0) for MK‐801 binding to the NMDA receptor. The relative potency of tricyclic compounds like MK‐801 for various neurotransmitter systems points out that the pharmacologic action of these drugs could involve complicated interactions in vivo.
Synaptic plasticity at crayfish neuromuscular junctions: Presynaptic inhibition
Authors: Baxter Douglas A. , Bittner George D. 
Published: December 2004

AbstractIntracellular recordings at sites electrotnically near terminals of the opener excitor axon in the claw of crayfish (Procambarus simulans) show that stimulation of the inhibitor neuron produces hyperpolarizing or depolarzing presynaptic inhibitory potentials (PIPs). GABA applied anywhere along the length of the opener excitor or inhibitor axons also produces hyperpolarizing or depolarizing potentials. The amplitude of action potentials (APs) at recording sites near some excitor terminals is reduced by an average of 6 mV during presynaptic inhibition, which also reduces excitatory postsynaptic Potentials (EPSPs) by 50–70%. The time course of AP reduction equals the time course of EPSP reduction and the amount of AP reduction is independent of the sign or amplitude of the PIPs. All these data are consistent with a hypothesis that a conductance increase produced by GABA in these presynaptic terminals of the excitor axon is responsible for presynaptic inhibition. However, the effect of presynaptic inhibition upon the accumulation of short‐term facilitation of excitatory transmitter release is not the same in all muscle fibers. In some terminals, the accumulation of Short‐term facilitation during shourt, high‐frequency trains of ction potentials which are presynaptically inhibited often equals the accumulation of facilitation without inhibition. In other terminals, short‐term facilitation accumulated during presynaptic inhibition often does not equal facilitation accumulated in the absence of presynaptic inhibition. These data suggest that some other factor which may contribute to presynaptic inhibition, such as a direct effect to decrease calcium currents, may also affect short‐term facilitation in some terminals.