Acetylcholine and GABA mediate opposing actions on neuronal chloride channels in crayfish.

A central principle of neural integration is that excitatory and inhibitory neurotransmitters effect the opening of distinct classes of membrane ionic channels and that integration consists of the summation of the opposing ionic currents on the postsynaptic membrane. In tangential cells of crayfish optic lobes, a hyperpolarizing, biphasic synaptic potential is produced by the concurrent action of acetylcholine and gamma aminobutyric acid (GABA). Acetylcholine hyperpolarizes the cell and increases chlorine conductance. GABA depolarizes the cell by closing some of the same chloride channels. Therefore, in this case integration is achieved by the antagonistic actions of two transmitters on the same ionic channel.

Tachykinin-related peptide and GABA-mediated presynaptic inhibition of crayfish photoreceptors.

Off-axis illumination elicits lateral inhibition at the primary visual synapse in crustacea and insects. The evidence suggests that the inhibitory action is presynaptic (i.e., on the photoreceptor terminal) and that the amacrine neurons of the lamina ganglionaris (the first synaptic layer) may be part of the inhibitory pathway. The neurotransmitters and the synaptic mechanisms are unknown. We show by immunocytochemistry that GABA and a tachykinin-related peptide (TRP) are localized in the amacrine neurons of the crayfish lamina ganglionaris. Indirect evidence suggests that GABA and TRP may be colocalized in these neurons. The extensive processes of the amacrine neurons occupy lamina layers containing the terminals of photoreceptors. Application of exogenous GABA and TRP to photoreceptor terminals produces a short-latency, dose-dependent hyperpolarization with a decay time constant on the order of a few seconds. TRP also exhibits actions that evolve over several minutes. These include a reduction of the receptor potential (and the light-elicited current) by approximately 40% and potentiation of the action of GABA by approximately 100%. The mechanisms of TRP action in crayfish are not known, but a plausible pathway is a TRP-dependent elevation of intracellular Ca(2+) that reduces photoreceptor sensitivity in arthropods. Although the mechanisms are not established, the results indicate that in crayfish photoreceptors TRP displays actions on two time scales and can exert profound modulatory control over cell function.

Motion detection and adaptation in crayfish photoreceptors. A spatiotemporal analysis of linear movement sensitivity.

Impulse and sine wave responses of crayfish photoreceptors were examined to establish the limits and the parameters of linear behavior. These receptors exhibit simple low pass behavior which is well described by the transfer function of a linear resistor-capacitor cascade of three to five stages, each with the same time constant (tau). Additionally, variations in mean light intensity modify tau twofold and the contrast sensitivity by fourfold. The angular sensitivity profile is Gaussian and the acceptance angle (phi) increases 3.2-fold with dark adaptation. The responses to moving stripes of positive and negative contrast were measured over a 100-fold velocity range. The amplitude, phase, and waveform of these responses were predicted from the convolution of the receptor's impulse response and angular sensitivity profile. A theoretical calculation based on the convolution of a linear impulse response and a Gaussian sensitivity profile indicates that the sensitivity to variations in stimulus velocity is determined by the ratio phi/tau. These two parameters are sufficient to predict the velocity of the half-maximal response over a wide range of ambient illumination levels. Because phi and tau vary in parallel during light adaptation, it is inferred that many arthropods can maintain approximately constant velocity sensitivity during large shifts in mean illumination and receptor time constant. The results are discussed relative to other arthropod and vertebrate receptors and the strategies that have evolved for movement detection in varying ambient illumination.

Immunocytochemical studies of the distribution of acetylcholine in the crayfish brain.

A number of studies indicate that acetylcholine is an important transmitter in most crustacean primary afferents and in at least several central pathways. Little is known, however, regarding the structure or distribution of cholinergic pathways in the central nervous system. The recent introduction of antibodies to choline-protein conjugates provides a potentially powerful means for localizing putative cholinergic neurons and pathways in the nervous system. Acetylcholine was localized with immunocytochemical procedures in the axons and terminals of cephalic primary afferents and in interneurons of the crayfish brain. The most intensely reactive loci were the primary sensory neuropiles, which contain the terminals of the statocyst afferents (parolfactory lobes) and antennal afferents (antennal lobe). These results are generally in accord with previous findings based upon choline uptake and enzyme assay in lobster cephalic nerves. We also found evidence consistent with the presence of acetylcholine in the globular interneurons of the accessory lobe and in descending interneurons which originate in the dorsal medial and anterior clusters of the protocerebrum. The axons of several neurons in the circumesophageal connective (descending interneurons and primary afferents) are also reactive to the choline antibody.

Pergolide in Parkinson's disease.

Twenty-two patients received pergolide mesylate for Parkinson's disease for one year. Improvement was maximal at six months, but average functional scores were still better at 12 months than at pretreatment evaluation. On-off fluctuations were reduced in severity, and two of 18 patients experienced full resolution. Pergolide is an effective and safe ongoing medication for Parkinson's disease.

Central nervous system magnetic resonance imaging findings in myotonic dystrophy.

We evaluated findings in 14 patients with myotonic dystrophy (MD) using magnetic resonance imaging of the brain and compared them with those in age-matched controls with headache. There was an increased incidence of ventriculomegaly and a lumpy and/or thick pattern of periventricular hyperintensity in patients with MD as compared with the age-matched controls. These white matter abnormalities do not appear to be etiologically specific, but some possible explanations for these frequent findings in MD are discussed.

Primary writing tremor: a selective action tremor.

Progressive difficulty in handwriting due to jerking movements precipitated by the act of writing beginning between the ages of 8 to 54 is reported in six patients. There was no rest tremor, but three had mild postural tremor. Specific muscle activity (especially pronation of the wrist or abduction of the fingers) elicited the tremors that persisted as long as the evocative posture or muscle activity was maintained. None had a family history of tremors, but two had a history suggestive of hypoxia at birth. Unlike benign essential tremor, the movements did not respond to propranolol HCl, but most patients were benefited both acutely and chronically by centrally active anticholinergic agents.

Elderly inpatients: postural reflex impairment.

We examined postural reflexes in 50 patients in a geriatric care facility. Patients aged 60 years and older who did not have orthostatic hypotension were subjected to a standing postural perturbation, and the degree of postural instability was recorded. Sixteen patients with leg amputations, recent stroke, and leg deformities were excluded. Of the remaining 34 patients, 44% had severe postural reflex impairment, and 24% had moderate impairment. Although the etiology for postural reflex impairment may be multivariant, the high percentage suggests that postural reflex dysfunction may be an important cause of unexplained falls in the elderly.

Meige syndrome (blepharospasm-oromandibular dystonia) after long-term neuroleptic therapy.

Two patients developed either blepharospasm or blepharospasm-oromandibular dystonia following chronic therapy with chlorpromazine, haloperidol, or thioridazine. In one patient, appearance of the movement disorder was associated with neuroleptic withdrawal, and in the other patient, the movement disorder began while neuroleptic therapy continued. Because of the age of one patient and the severe intermittent psychosis in the other, these Meige-like symptoms were attributed to chronic neuroleptic use rather than to spontaneously occurring Meige syndrome. The symptoms occurring as part of a tardive dyskinesia suggest that dopaminergic mechanisms play a role in idiopathic Meige syndrome.

Meige disease: acute and chronic cholinergic effects.

We studied central cholinergic systems in 13 patients with idiopathic adult-onset blepharospasm/oromandibular dystonia (Meige syndrome). Six patients studied acutely, and 12 of 13 patients studied chronically, improved after administration of centrally acting anticholinergic agents. These data suggest that Meige syndrome is pharmacologically similar to other dystonic disorders, in which central cholinergic antagonism is more consistently of benefit than manipulation of central dopaminergic systems.

Chronic agonist therapy for Parkinson's disease: a 5-year study of bromocriptine and pergolide.

We used pergolide to treat 10 patients with idiopathic Parkinson's disease who had first responded to, and then failed, bromocriptine therapy. At the end of 5 years, patients had improved when compared with study entry. Peak efficacy, equal with both drugs, was seen at 12 months. After a mean treatment of 29 months, bromocriptine was no longer effective, but pergolide was still beneficial.

Drug-induced asterixis in Parkinson disease.

Asterixis was observed in five parkinsonian patients who were taking levodopa. A prospective study revealed that 4 of 55 consecutive patients had asterixis. Liver and metabolic functions were normal in all patients. Asterixis always occurred as part of a toxic confusional state superimposed on a parkinsonian state associated with some dementia. Insomnia, hallucinosis, and myoclonus were also prominent in the affected patients. Because of this association with other signs of chronic drug toxicity and its reversal with drug withdrawal, the asterixis seemed to be drug-related.

Pergolide mesylate and idiopathic Parkinson disease.

We studied the effects of pergolide mesylate in an open trial of 23 patients with idiopathic Parkinson disease (PD). All had suffered from loss of efficacy or dose-limiting side effects on current antiparkinsonian regimens. On pergolide therapy, improvement, which was maintained for 6 months, was noted in some parkinsonian features in all 23 patients. All patients suffering from on-off phenomenon were helped by pergolide. Significant side effects were not encountered. Pergolide is useful in the treatment of PD.

Intrafamilial heterogeneity in hereditary motor neuron disease.

Although there are varied inheritance patterns in motor neuron disease (MND), the phenotype of MND is reported to be constant within these families, ie, cases of amyotrophic lateral sclerosis or primary lateral sclerosis do not occur in pedigrees with cases of spinal muscular atrophy. We describe four pedigrees whose members diverged in the phenotype of MND expressed. The intrafamilial variation of phenotype suggests a similar pathogenesis for some of the varied types of familial MND and the need for careful inquiry of family history in all patients with MND.

Chronic dopaminergic sensitivity after Sydenham's chorea.

We studied psychometric performance on the Minnesota Multiphasic Personality Inventory (MMPI) mini-mult and drug-induced choreic reactions in a group of patients with a history of Syndenham's chorea. Action tremor, motor signs, and residual chorea were common. One-half of the patients reported adverse choreic reactions to one or more agents. Patients with adverse reactions to central stimulants and anorectics had statistically significant elevations in the psychotic tetrad of the MMPI. Sydenham's chorea in childhood seems to confer persistent sensitivity to agents that augment central dopaminergic activity, which may be expressed as acute chorea. Central dopaminergic sensitivity may explain earlier reports of psychologic difficulties in survivors of rheumatic chorea.

PIP: 32 patients with Sydenham's chorea were studied at the La Rabida Institute for psychometric performance on the Minnesota Multiphasic Personality Inventory (MMPI). Questionnaires used included a definition of chorea and a description of choreic movements which the patients and members of their households were asked to read. Results were: 1) the only medical condition frequently reported was arthritis; 20/32 patients reported medical consultation for this complaint; 2) 19 patients including 2 with chorea gravidium, reported motor or psychiatric side effects from 1 or more agents; 3) in patients with multiple drug exposures a history of adverse motor reactions to decongestants was always associated with adverse reactions to anorectics or amphetamine in patients with exposure to all agents, and a similar pattern was noted with thyroid hormone and oral contraceptives (OCs); 4) 1 patient with chorea gravidium reported dyskinesias after administration of decongestants or amphetamine but tolerated OCs; and 5) MMPI scores from patients reporting adverse responses to amphetamines were statistically elevated in the psychotic tetrad. This study provides support for the belief that Sydenham's chorea is not a benign self-limited disease of childhood. In addition to mild residual neurologic abnormalities, the disorder appears to confer long-standing sensitivity to a variety of dopaminergically active agents.

Respiratory dyskinesia presenting as acute respiratory distress.

Incapacitating respiratory distress was the presenting manifestation of a choreiform movement disorder. Because the patient also had asthma, respiratory distress was at first mistakenly attributed to this condition. Despite vigorous asthma management, there was no improvement. However, once the neurologic condition was recognized, use of specific therapy (haloperidol and reserpine) resulted in rapid and sustained remission of respiratory symptoms.

Dye coupling and gap junctions between crustacean neurosecretory cells.

Neurosecretory cells in the X organ-sinus gland system of the crayfish were impaled and Lucifer Yellow was intracellularly iontophoresed. In some neurons the injected dye was transferred to neighboring neurons. The interneuronal dye transfer was between adjacent somata. Coupling was also observed between neurons and smaller cells, possibly glia. Gap junctions were identified by freeze-fracture in neuron somata and glial cells in the X organ and also in neurosecretory axons in the sinus gland.

Light input to crustacean neurosecretory cells.

Electrical activity was recorded intracellularly from neurosecretory cells in the crayfish eyestalk identified by lucifer yellow injection. The activity is most commonly enhanced by illumination of retinal fields. Increments in spontaneous activity as well as bursts in otherwise silent cells were the most common type of response. Occasionally light-induced inhibitory responses were recorded. At neuropil level, light pulses result in EPSPs with amplitudes dependent on intensity of light and the previous adaptation to darkness.

A quantitative correlation of contour sensitivity with dendritic density in an identified visual neuron.

Crayfish sustaining fibers are visual interneurons that are tonically excited by increases in illumination within their receptive fields. The receptive fields of sustaining fibers (SFs) are correlated with the two-dimensional position of their dendritic fields within the central neuropil. Dendritic branching patterns and contour sensitivity maps were obtained for SF 019 in several preparations. The contour sensitivity along the dorsal-ventral visual arc (which intersects 019's receptive field) is positively correlated with the variations in the spatial frequency of 019's dendritic arbor along the dorsal ventral midline of the neuropil. We conclude that an SF's receptive field is determined by the position and extent of its dendritic field and that sensitivity variations within the receptive field are principally determined by changes in its dendritic density.

A neuronal nicotinic acetylcholine receptor in crayfish neurons.

In warm-blooded vertebrates, neuronal nicotinic acetylcholine receptors (nAChRs) are distinguished from muscle endplate receptors by their ligand affinities and sensitivity to several toxins. In the crayfish optic lobe, synaptic and acetylcholine (ACh)-elicited responses are blocked by toxins (F-toxin and neosurugatoxin) selective for neuronal nAChRs and are insensitive to the alpha-neurotoxins selective for endplate nAChRs.