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At least 55 records · Page 3Linked to original sources
PubMed1976

Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.

"Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded "Dale's Principle": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)...

5-Hydroxytryptophan↗
PubMed1978

Synaptic transmission without action potentials: input-output properties of a nonspiking presynaptic neuron.

1. Input-output properties of the inhibitory synaptic connection between non-spiking neurons (EX1) and gastric mill (GM) neurons were examined in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Current was injected into and the voltage was recorded during current injection, two independent microelectrodes were used. 2. The EX1-GM synaptic connection is a conductance-increase inhibitory type, with an input-output curve that resembles the curve for the squid giant synapse. There is a threshold level of depolarization for transmitter release from the presynaptic cell. Beyond that threshold, increasing presynaptic depolarization causes increasing postsynaptic hyperpolarization (and inhibition). 3. A long presynaptic current step always causes a postsynaptic response with an initial peak of hyperpolarization followed by a decay to a less hyperpolarized plateau level. The plateau level is maintained, in most cells, for the duration of the presynaptic depolarization even over long periods (30 s). 4. The peak, but not the plateau, part of the postsynaptic response is sensitive to the past history of the synaptic connection. If a large conditioning pulse is applied to the presynaptic cell causing a large postsynaptic hyperpolarization, then the postsynaptic response to a later presynaptic test depolarization will have a reduced peak, leaving the plateau component unchanged.

Animals↗
PubMed1978

Synaptic transmission to the horizontal cells in the retina of the larval tiger salamander.

1. The receptive field diameter for most horizontal cells far exceeds the lateral spread of processes for any cell. Therefore horizontal cells probably receive synaptic input from neighbours as well as from the photoreceptors. The electrical effects of these two synaptic inputs were studied. 2. We have characterized the electrical properties of the horizontal cell inputs by determining the current-voltage curves in dark and light. These curves were compared with those obtained in the presence of Co2+ or Mg2 was nearly identical to the curve in the light. 4. The putative transmitter substances glutamate, aspartate and GABA depolarized the cells by increasing conductance. Current-voltage curves measured in the presence of these substances intersected the dark and light curves at +50 mV, the same level at which the dark and light curves intersect. 5. The light response of cells uith broad receptive fields, between 1.0 and 2.0 mm, showed little or no change in conductance associated with the light response. The input resistance was near 20 Momega, and the current-voltage curves intersected at an extrapolated potential level near 200 mV. 6. In the presence of ACh, electrical properties of the broad field cells reverted to those of the narrow field cells: the receptive field was reduced to 0.5 mm, the imput resistance increased, and the current-voltage curves intersected near +50 mV. Thus ACh appeared to interrupt synaptic input from neighbouring horizontal cells. 7. The results confirm the suggestion that horizontal cells receive a tonic excitatory input from the photoreceptors which is decreased by light. They show that horizontal cells receive an additional input from their neighbours, not associated with a measurable conductance change. The input from neighbours is selectively interrupted by ACh, but the nature of this synapse and of the cholinergic action is not known.

Acetylcholine↗
PubMed1976

Synaptic transmission between rat superior cervical ganglion neurons in dissociated cell cultures.

The principal neurons of the rat superior cervical ganglion (SCGN) when established as dissociated cells in tissue culture form synapses among themselves. In the present study we have examined this synaptic interaction when these neurons are co-cultured with several other types of tissues. Dissociated SCGN were prepared from perinatal rats and studied, after 3-4 weeks maturation, with intracellular recording techniques. Synaptic interactions between sympathetic neurons were demonstrated when these cells were: (a) grown with explants from newborn rat thoracic spinal cord, (b) when the SCGN had survived for several weeks subsequent to removal of the spinal cord explants, and (c) when the SCGN were grown in the presence of an adrenergic target (interscapular brown fat cells). Unidirectional, reciprocal, recurrent and complex chemical synaptic networks, consisting of convergence and divergence, characterized connections between SCGN. All synaptic responses were cholinergic since they were reversibly blocked by hexamethonium or mecamylamine but were not sensitive to 10(-5) M phenoxybenzamine. Removal of the spinal cord explants did not significantly alter the proportion of chemical synaptic interactions between SCGN (more than 25%) from matched cultures. Anatomical observations established that in cultures with brown fat, innervating neurites appeared on the fat cells; these neurites frequently expanded to form varicosities that resembled the adrenergic terminals normally seen on brown fat in the animal. Synaptic profiles also occurred on the neurons in these cultures and some of these were shown to be cholinergic. The proportion of neuronal interactions in the combined SCGN + fat cultures was low, however, suggesting that co-culture with target tissue might influence the frequency of interconnections developed between SCGN in culture. Other factors, such as the presence of non-neuronal cells, degree of dissociation, cellular density, culture age and the survival of certain types of SCGN in culture are discussed as variables related to the formation of synapses between SCGN. Non-rectified electrical coupling between SCGN was also observed in 17 out of 679 pairs (2.5%) of neurons. Attenuation factor for electrically coupled action potentials ranged between 1 and 43.5.

Adipose Tissue, Brown↗