Adenosine 3',5'-monophosphate: electrophysiological evidence for a role in synaptic transmission

Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses.     

Plasticity of substance P in mature and aged sympathetic neurons in culture

The effect of age on the plasticity of the putative peptide neurotransmitter substance P (SP) was examined in the rat superior cervical sympathetic ganglion. Explantation of ganglia from 6-month-old rats to serum-supplemented culture resulted in a tenfold increase in SP concentration, reproducing results previously obtained for ganglia from neonatal rats. Veratridine prevented the increase in SP concentration in adult ganglia, and tetrodotoxin blocked the veratridine effect, suggesting that membrane depolarization and sodium influx prevented the rise in the SP content of adult ganglia as well as of neonatal ganglia. However, the time courses of the increase in the amount of the peptide differed in neonatal and mature ganglia, suggesting that some aspects of regulation may differ in the two. The effects of aging on neural plasticity were further analyzed by explanting ganglia from 2-year-old rats. No significant increase in SP concentration was observed in these ganglia. Remarkable plasticity thus seems to persist in mature neurons but may be deficient in aged sympathetic neurons.     

Neurotransmitter plasticity at the molecular level

Contrary to long-held assumptions, recent work indicates that neurons may profoundly change transmitter status during development and maturity. For example, sympathetic neurons, classically regarded as exclusively noradrenergic or cholinergic, can also express putative peptide transmitters such as substance P. This neuronal plasticity is directly related to membrane depolarization and sodium ion influx. The same molecular mechanisms and plastic responses occur in mature as well as developing neurons. Further, contrary to traditional teaching, adult primary sensory neurons may express the catecholaminergic phenotype in vivo. Transmitter plasticity is not restricted to the peripheral nervous system: ongoing studies of the brain nucleus locus ceruleus in culture indicate that specific extracellular factors elicit marked transmitter changes. Consequently, neurotransmitter expression and metabolism are dynamic, changing processes, regulated by a variety of defined factors. Transmitter plasticity adds a newly recognized dimension of flexibility to nervous system function.     

山羊感觉和交感神经节中的肽类免疫反应结构

所有背根节和迷走神经结状节出现大量P物质(SP)阳性胞体和纤维,小细胞占92％,大中型细胞占8％,仅有极少数生长抑素(SS)样神经胞体。大量含SP的纤维和终未见于颈上节和腹腔-前肠系膜神经节,但含SS的纤维和终末主要见于腹腔-前肠系膜神经节,颈上节甚少。交感节中无SP和SS阳性胞体。出现于交感神经节中的SP和SS纤维和终末,可能来自背根节初级感觉神经元的外周侧支或肠神经元。按照这个模式,SP和SS可通过不涉及中枢神经系统的外周短反射环路;去调节交感神经的反应。     

D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.     

Substance P and somatostatin regulate sympathetic noradrenergic function

Peptidergic-noradrenergic interactions were examined in explants of rat sympathetic superior cervical ganglia and in cultures of dissociated cells. The putative peptide transmitters substance P and somatostatin each increased the activity of the catecholamine-synthesizing enzyme tyrosine hydroxylase after 1 week of exposure in culture. Maximal increases occurred at 10(-7) molar for each peptide, and either increasing or decreasing the concentration reduced the effects. Similar increases in tyrosine hydroxylase were produced by a metabolically stable agonist of substance P, while a substance P antagonist prevented the effects of the agonist. The data suggest that the increased tyrosine hydroxylase activity was mediated by peptide interaction with specific substance P receptors and that peptides may modulate sympathetic catecholaminergic function.     

Putamen: activity of single units during slow and rapid arm movements

The activity of putamen neurons was studied in a monkey during the performance of both slow and rapid arm movements. More than half of all movement-related units discharged preferentially in relation to slow movements and less than 10 percent in relation to rapid movements. These findings indicate that at least a portion of the basal ganglia (the putamen) is primarily involved in the control of slow movements and are consistent with the hypothesis of Kornhuber that the primary motor function of the basal ganglia is to generate slow ("ramp") rather than rapid ("ballistic") movements.     

Nerve growth factor attenuates neurotoxic effects of taxol on spinal cord-ganglion explants from fetal mice

Most neurons in organotypic cultures of dorsal root ganglia from 13-day-old fetal mice require high concentrations of nerve growth factor for survival during the first week after explanation. These nerve growth factor-enhanced sensory neurons mature and innervate the dorsal regions of attached spinal cord tissue even after the removal of exogenous growth factor after 4 days. In cultures exposed for 4 days to nerve growth factor and taxol (a plant alkaloid that promotes the assembly of microtubules) and returned to medium without growth factor, greater than 95 percent of the ganglionic neurons degenerated and the spinal cord tissues were reduced almost to monolayers. In contrast, when the recovery medium was supplemented with nerve growth factor, the ganglionic neurons and dorsal (but not ventral) cord tissue survived remarkably well. Dorsal cord neurons do not normally require an input from dorsal root ganglia for long-term maintenance in vitro, but during and after taxol exposure they become dependent for survival and recovery on the presence of neurite projections from nerve growth-factor-enhanced dorsal root ganglia.     

Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions

A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.     

Xenopus oocytes injected with rat uterine RNA express very slowly activating potassium currents

Under the influence of estrogen, uterine smooth muscle becomes highly excitable, generating spontaneous and prolonged bursts of action potentials. In a study of the mechanisms by which this transition in excitability occurs, polyadenylated RNA from the uteri of estrogen-treated rats was injected into Xenopus oocytes. The injected oocytes expressed a novel voltage-dependent potassium current. This current was not observed in oocytes injected with RNA from several other excitable tissues, including rat brain and uterine smooth muscle from ovariectomized rats not treated with estrogen. The activation of this current on depolarization was exceptionally slow, particularly for depolarizations from relatively negative membrane potentials. Such a slowly activating channel may play an important role in the slow, repetitive bursts of action potentials in the myometrium.     

Dopamine modulation of the effects of gamma-aminobutyric acid on substantia nigra pars reticulata neurons

Studies were conducted to assess whether basal ganglia output neurons originating in the substantia nigra pars reticulata might be affected by dopamine released from dendrites of neighboring substantia nigra pars compacta neurons. Dopamine applied by iontophoresis increased the baseline firing rates of approximately half of the substantia nigra pars reticulata cells tested. The more significant finding, unrelated to the increase in firing, was the ability of dopamine to attenuate the inhibitory responses of these cells to iontophoretically applied gamma-aminobutyric acid. These findings suggest a role for dopamine as a neuromodulator and further suggest that it can act at sites beyond the striatum to modify transmission from the basal ganglia to motor nuclei.     

奶山羊颈交感干节后纤维的起源——用HRP法研究

将HRP注入奶山羊颈交感干后,在注射侧的颈中神经节、星状神经节、T_(2-5)椎旁节以及交感干中可见数量不等的标记细胞.其中以颈中、星状神经节标记细胞最多。椎旁节中的标记细胞向尾侧逐渐减少,交感干的标记细胞以弥散方式存在。在颈前节中未见标记细胞。以上结果表明,颈交感干中含有起于颈中神经节、星状神经节、T2—5椎旁节以及交感干上散在的小神经节的上行节后纤维。     

Depolarization without calcium can release gamma-aminobutyric acid from a retinal neuron

Calcium influx is often an essential intermediate step for the release of neurotransmitter. However, some retinal neurons appear to release transmitter by a mechanism that does not require calcium influx. It was uncertain whether depolarization released calcium from an intracellular store or released transmitter by a mechanism that does not require calcium. The possibility that voltage, and not calcium, can regulate the release of transmitter was studied with pairs of solitary retinal neurons. Horizontal and bipolar cells were isolated from fish retinas and juxtaposed in culture. Communication between them was studied with electrophysiological methods. A horizontal cell released its neurotransmitter, gamma-aminobutyric acid, when depolarized during conditions that buffered the internal calcium concentration and prohibited calcium entry. The speed and amount of material released were sufficient for a contribution to synaptic transmission.     

Nerve trophic function: in vitro assay of effects of nerve tissue on muscle cholinesterase ctivity

The effects of tissue explants and nerve homogenates on cholinesterase activity of muscle of the newt Triturus in organ culture were measured. Sensory ganglia, ganglia separated from muscle by a Millipore filter, spinal cord, liver, and nerve homogenates produced greater activity of muscle cholinesterase than occurred in untreated muscle cultured for the same period of time. Boiled ganglia, kidney, oviduct, and spleen were ineffective. This procedure serves as a convenient bioassay for a neurotrophic process and indicates that the trophic effect is mediated by a diffusible chemical substance produced by nerves.     

Inferior olive of the cat: intracellular recording

The action potential evoked from inferior olivary neurons of the cat by orthodromic, antidromic, or intracellular stimulation has a large prolonged depolarization, frequently with several superimposed smaller spikes. The all-or-nothing unitary response appears to be a property of the cell, and the later spikes are not secondary to synaptic excitation by recurrent axon collaterals.     

Odor-induced membrane currents in vertebrate-olfactory receptor neurons

In olfactory receptor neurons, odor molecules cause a depolarization that leads to action potential generation. Underlying the depolarization is an ionic current that is the earliest electrical event in the transduction process. In two preparations, olfactory receptor neurons were voltage-clamped and stimulated with odors and this generator current was measured. In addition, a method was developed to estimate the time course and absolute concentration of odorants delivered to the receptor sites. With this method, olfactory neurons were found to have relatively high stimulus thresholds, steep dose-response relations, long latencies, and an apparent requirement for cooperativity at one or more steps in the pathway from odorant binding to activation of the generator current.     

Depolarization and muscarinic excitation induced in a sympathetic ganglion by vasoactive intestinal polypeptide

The effects of vasoactive intestinal polypeptide (VIP) in the superior cervical ganglion of the cat were studied in vitro and in vivo with sucrose gap and multiunit recording, respectively. At a dose of 0.03 to 0.12 nanomole, VIP produced a dose-dependent, prolonged (3 to 15 minutes) depolarization of the ganglion and enhanced the ganglionic depolarization elicited by the muscarinic agonist acetyl-beta-methylcholine. At a dose of 1.8 to 10 nanomoles, the peptide enhanced and prolonged the postganglionic discharge elicited by acetyl-beta-methylcholine, enhanced muscarinic transmission in ganglia treated with an anticholinesterase agent, and enhanced the late muscarinic discharge elicited by acetylcholine. VIP did not affect the early nicotinic discharge elicited by acetylcholine or by electrical stimulation of the preganglionic nerve. It is concluded that VIP has a selective facilitatory action on muscarinic excitatory mechanisms in the superior cervical ganglion of the cat.     

Vasoactive intestinal peptide alters membrane potential and cyclic nucleotide levels in retinal horizontal cells

Vasoactive intestinal peptide stimulated the synthesis of adenosine 3',5'-monophosphate in fractions of isolated carp horizontal cells. When applied extracellularly to isolated and cultured horizontal cells, the peptide also induced a slow depolarization (30 to 40 millivolts) accompanied by a decrease in membrane resistance. However, analogs of adenosine 3',5'-monophosphate applied extracellularly or intracellularly, and forscolin applied extracellularly, had no effect on the membrane potential of cultured horizontal cells, indicating that the induced depolarization was not related to the accumulation of adenosine 3',5'-monophosphate in these cells.     

Presynaptic inhibition: primary afferent depolarization in crayfish neurons

Inhibition of transmission between tactile sensory neurons and interneurons in the crayfish was investigated by intracellular recording int the presynaptic processes. Inhibition is correlated with a depolarization of the presynaptic process, as in the mammalian spinal cord; the depolarization is accompanied by a conductance increase, and is mediated by interneurons that can be excited by a variety of routes.