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Patients with Parkinson’s disease (PD) often underestimate time intervals, however it remains unclear why they underestimate rather than overestimate them. The current study examined time underestimation and counting in patients with PD, in relation to dopamine transporter (DaT) located on presynaptic nerve endings in the striatum. Nineteen non-dementia patients with PD and 20 age- and sex-matched healthy controls performed two time estimation tasks to produce or reproduce time intervals with counting in the head, to examine dysfunctional time counting processing. They also performed tapping tasks to measure cycles of counting with 1 s interval with time estimation. Compared to controls, patients underestimated time intervals above 10 s on time production not reproduction tasks and the underestimation correlated with fast counting on the tapping task. Furthermore, striatal DaT protein levels strongly correlated with underestimation of time intervals. These findings suggest that distortion of time intervals is guided by cumulative output of fast cycle counting and that this is linked with striatal DaT protein deficit.

Neuromuscular junctions in the extensor digitorum longus muscle of control and dystrophic (dy) mice at stages ranging from 30 to 120 postnatal days were examined by scanning and transmission electron microscopy (SEM and TEM). In control mice, the neuromuscular junctions consisted of thin ramifying nerve endings and of complex labyrinthine gutters with a great number of slit-like junctional folds. The subneural apparatuses of dy mice on the 30th and the 60th postnatal days were composed of undeveloped gutters or a number of cup-like depressions containing a few pit-like or slit-like junctional folds. In dystrophic neuromuscular junctions on the 120th postnatal day, subneural apparatuses were classified into two types: one had a cluster of continuous cup-like depressions with or without slit-like junctional folds, and the other consisted of discrete depressions containing slit-like junctional folds. Moreover, a small number of dystrophic muscle fibers were endowed with two subneural apparatuses which were 20 to 30 microns away from each other. Small round pits (0.5-1.0 microns in diameter) in some cup-like depressions were occasionally protruded by short processes of terminal axons. The present findings suggest that the age-dependent postsynaptic structural changes of dystrophic dy mice induce a complex morphological reorganization of presynaptic nerve endings. This might help the nerve endings compensate for the functional deterioration of dystrophic muscle fibers.

— Several parameters of GABA Auxes across the synaptosomal membrane were studied using synaptosomes prepared from the brain of immature (8-day-old) rats. The following aspects of GABA carrier-mediated transport were similar in immature and mature synaptosomes: (1) magnitude of [3H]GABA accumulation; (2) GABA homoexchange in normal ionic conditions; (3) GABA homoexchange in the presence of cationic fluxes (Na+ and Ca2+ influx, K+ efflux) characteristic of physiological depolarization. As in adult synaptosomes (Levi & Raiteri, 1978), in these conditions the stoichiometry of GABA homoexchange was in the direction of net outward transport (efflux > influx). The essential differences between the behaviour of 8-day-old and adult synaptosomes were the following: (1) β-alanine (a glial uptake inhibitor) inhibited GABA uptake in immature synaptosomes (the inhibition being greater in crude than in purified preparations) and was without a significant effect in adult synaptosomes. DABA and ACHC (two neuronal uptake inhibitors) depressed GABA uptake more efficiently in purified than in crude immature synaptosomes, but were as effective in crude and purified nerve endings from adult animals. The data suggest a greater uptake of GABA in the‘gliosomes’contaminating the synaptosomal preparations from immature animals. (2) In immature synaptosomes prelabelled with [3H]GABA the specific radioactivity of the GABA released spontaneously or by heteroexchange (with 300 μm-OH-GABA) was the same as that present in synaptosomes, while in adult synaptosomes OH-GABA released GABA with increased specific radioactivity. The data suggest a homogeneous distribution of the [3H]GABA taken up within the endogenous GABA pool in immature, but not in mature synaptosomes. (3) In immature synaptosomes the release of GABA (radioactive and endogenous) induced by depolarization with high KC was not potentiated by Ca2+, unless the synaptosomes had been previously depleted of Na+ These data suggest that, although a Ca2+ sensitive pool of GABA may be present, this pool is not susceptible to being released in normal conditions, probably because the high intrasynaptosomal Na+ level prevents a sufficient depolarization. The possible significance of these findings in terms of functional activity of GABAergic neurotransmission in the immature brain is discussed.

(Na+-K+) ATPase is present in synaptosomal preparations and it is assumed to represent the sodium-potassium pump. 10 microM-noradrenaline activates (Na+-K+) ATPase approximately 100%, but 50 microM-noradrenaline does not stimulate the rate of 22Na extrusion from synaptosomes. The results suggest that it is unlikely that the noradrenaline stimulation of (Na+-K+) ATPase is part of a feedback mechanism whereby released noradrenaline can influence the activity of the presynaptic sodium pump.

Potassium concentrations above 15-20 mM in the medium, or addition of 75 μM veratridine to medium that contains 5 mM K, stimulate calcium accumulation and Ca-dependent norepinephrine release by presynaptic nerve terminals (synaptosomes) incubated in vitro . The effects of veratridine, but not of K, are blocked by 0.2 μM tetrodotoxin. This association between Ca entry and norepinephrine release is consistent with the Calcium Hypothesis of transmitter release. These results add further evidence that synaptosomes may retain many functional properties of intact presynaptic endings.

Presynaptic nerve endings in the ciliary ganglia of chick embryos are 3-dimensionally examined by scanning electron microscopy. Underdeveloped nerve endings attached to the lateral side of the ciliary cells are spoon-like, and show an irregular surface texture and marginal outline with many slender processes and pores. Well-developed nerve endings embracing more than half of the surface of the ciliary cell are cup-like, and show a smooth surface texture and a linear marginal outline with few slender processes and pores. The slender processes come into intimate contact with each other at the margin of the spoon-like nerve endings or cross the pores, seemingly expanding and smoothing the nerve endings. Cytoplasmic processes of the ciliary cells are also described.

In den oberen zervikalen Ganglien der Katze verursacht eine Perfusion mit Locke-Losung mit 0.1 mM Quecksilber Chlorid eine spontane Freisetzung von Acetylcholin. Dieses Phanomen wird vom Standpunkt der bekannten Wirkung anderer Metalionen bei der Freisetzung von Transmittern diskutiert.

The isolation of synaptic vesicles from mouse brain by a modification of previously reported methodology is described. Homogeneity of the preparations was ascertained by electron microscopy. Vesicles thus isolated contained cyclic AMP (365 ± 44 pmol/mg of protein; mean ± S.E.M.) and adenosine 3′,5′-monophosphate phosphodiesterase activity (500 pmol/mg of protein per 30 min). The number of vesicles in three of the vesicle preparations was determined by a visual count of grid fields under the electron microscope. The content of cyclic AMP in the vesicles was calculated at 5000-7500 molecules/vesiclc. The presence of cyclic AMP in the synaptic vesicles from presynaptic nerve endings would support a role for this nucleotide in nerve transmission.