Highlights • We used dopamine D2 receptor knock-out mice. • We examined frequency-dependent suppression of striatal inhibitory transmission. • Physiologically released dopamine modulates synaptic ...transmission and neuronal firing. • Modulation of transmission by dopamine is tightly coupled to N-type calcium channels.
Pluto and its satellite, Charon (discovered in 1978; ref. 1), appear to form a double planet, rather than a hierarchical planet/satellite couple. Charon is about half Pluto's size and about ...one-eighth its mass. The precise radii of Pluto and Charon have remained uncertain, leading to large uncertainties on their densities. Although stellar occultations by Charon are in principle a powerful way of measuring its size, they are rare, as the satellite subtends less than 0.3 microradians (0.06 arcsec) on the sky. One occultation (in 1980) yielded a lower limit of 600 km for the satellite's radius, which was later refined to 601.5 km (ref. 4). Here we report observations from a multi-station stellar occultation by Charon, which we use to derive a radius, RC = 603.6 ± 1.4 km (1σ), and a density of ρ = 1.71 ± 0.08 g cm-3. This occultation also provides upper limits of 110 and 15 (3σ) nanobar for an atmosphere around Charon, assuming respectively a pure nitrogen or pure methane atmosphere.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Whole‐cell patch‐clamp recordings of GABAergic IPSCs were made from cholinergic interneurones in slices of striatum from developing rats aged 21‐60 days postnatal. In addition, the Ca2+ channel ...subtypes involved in synaptic transmission, as well as dopamine (DA)‐induced presynaptic inhibition, were investigated pharmacologically with development by bath application of Ca2+ channel blockers and DA receptor agonists. The IPSC amplitude was reduced by ω‐conotoxin GVIA (ω‐CgTX) or ω‐agatoxin TK (ω‐Aga‐TK) across the whole age range, suggesting that multiple types of Ca2+ channels mediate transmission of the synapse. The IPSC fraction reduced by ω‐CgTX significantly decreased, whereas that reduced by ω‐Aga‐TK remained unchanged with development. DA or quinpirole, a D2‐like receptor agonist, presynaptically reduced the IPSC amplitude throughout development. The DA‐induced inhibition decreased with age in parallel with the decrease in N‐type Ca2+ channels. DA showed no further inhibition of IPSCs after the inhibitory effect of ω‐CgTX had reached steady state throughout development. These results demonstrate that there is a functional link between presynaptic N‐type Ca2+ channels and D2‐like DA receptors at inhibitory synapses in the striatum. They also demonstrate that the suppression of GABAergic transmission by D2‐like receptors is mediated by modulation of N‐type Ca2+ channels and decreases in parallel with the developmental decline in the contribution of N‐type Ca2+ channels to exocytosis.
1. Excitatory postsynaptic currents (EPSCs) following focal afferent stimulation were recorded from patch-clamped magnocellular
neurones in a thin-slice preparation of the rat basal forebrain. Evoked ...EPSCs had a mean decay time constant of 3.81 +/- 0.09
ms and were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 microM). 2. Bath-applied dopamine (DA) reduced
evoked EPSC amplitude by up to 54.2 +/- 2.3% with an IC50 of 19.9 microM in normal Krebs solution (2.5 mM Ca2+, 1.2 mM Mg2+)
without effect on postsynaptic holding current. 3. DA (30 microM) reduced the mean frequency of spontaneous miniature EPSCs
recorded in 0.5 microM tetrodotoxin without affecting their mean amplitude, rise time or decay time constant. This effect
was diminished by 100 microM Cd2+. 4. The effect of DA on evoked EPSCs was mimicked by the D1-like receptor agonist, SKF 81297
(IC50 25.6 microM), but not by the D2-like receptor agonist R(-)-TNPA (30 microM) or (-)-quinpirole (30 microM), and was antagonized
by the D1-like receptor antagonist R(+)-SCH 23390 (estimated dissociation constant KB = 1.7 microM) but not by the D2-like
receptor antagonist S(-)-eticlopride (10 microM). 5. Forskolin (10 microM) reduced evoked EPSCs to approximately 60% of the
control amplitude, and occluded the effect of subsequent application of DA. 6. These results suggest that glutamatergic afferents
to magnocellular basal forebrain neurones possess presynaptic D1-like DA receptors, and that activation of these receptors
reduces excitatory glutamatergic transmission, probably via an adenylyl cyclase-dependent pathway.
Laparoscopic intragastric surgery (LIGS) was performed on a 63-year-old man with a gastric leiomyoma adjacent to the cardia. Because the tumor was about 5 cm in maximum diameter and showed ...ulceration, the possibility that the tumor was a leiomyosarcoma could not be ruled out preoperatively. Conventionally, major surgery has been performed on patients with a tumor located near the cardia, although it was not always malignant. Enucleation by LIGS enabled us to avoid excessive invasiveness and provided a favorable result. LIGS may be an appropriate new, minimally-invasive operation for gastric myogenic tumors and should be considered for such cases.
Deletions in the DAP12 gene in humans result in Nasu-Hakola disease, characterized by a combination of bone fractures and psychotic symptoms similar to schizophrenia, rapidly progressing to presenile ...dementia. However, it is not known why these disorders develop upon deficiency in DAP12, an immunoreceptor signal activator protein initially identified in the immune system. Here we show that DAP12-deficient (DAP12 super(-/-)) mice develop an increased bone mass (osteopetrosis) and a reduction of myelin (hypomyelinosis) accentuated in the thalamus. In vitro osteoclast induction from DAP12 super(-/-) bone marrow cells yielded immature cells with attenuated bone resorption activity. Moreover, immature oligodendrocytes were arrested in the vicinity of the thalamus, suggesting that the primary defects in DAP12 super(-/-) mice are the developmental arrest of osteoclasts and oligodendrocytes. In addition, the mutant mice also showed synaptic degeneration, impaired prepulse inhibition, which is commonly observed in several neuropsychiatric diseases in humans including schizophrenia, and aberrant electrophysiological profiles in the thalami. These results provide a molecular basis for a unique combination of skeletal and psychotic characteristics of Nasu-Hakola disease as well as for schizophrenia and presenile dementia.
The effects of dopamine (DA) on non‐NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole‐cell ...patch‐clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 μM CNQX in the presence of bicuculline (20 μM), strychnine (0.5 μM) and D‐amino‐5‐phosphonopentanoic acid (D‐AP5, 25 μM).
Bath application of DA reduced the amplitude of EPSCs up to 65.1 ± 9.52% in a concentration‐dependent manner between 0.3‐1000 μM (IC
50
, 16.0 μM) without affecting the holding current at −60 mV measured using a Cs
+
‐filled electrode.
The effect of DA on evoked EPSCs was mimicked by the D
2
‐like receptor agonist quinpirole but not by the D
1
‐like receptor agonist SKF 81297, and was antagonized by the D
2
‐like receptor antagonist sulpiride (
K
B
, 0.96 μM), but not by the D
1
‐like receptor antagonist SCH 23390 (
K
B
, 228.6 μM).
Dopamine (30 μM) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DA‐induced effect on the mEPSCs was dependent on the external Ca
2+
concentration.
These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D
2
‐like receptors, activation of which inhibits glutamate release by reducing Ca
2+
influx.
1
An intracellular recording study was performed to elucidate the mechanism underlying D1 and D2 receptor‐mediated inhibition of neuronal activities of dopaminergic neurones in the ventral tegmental ...area (VTA) using slice preparations of the rat brain.
2
VTA neurones were classified into type I and type II neurones according to the shape of the action potential, which correspond to dopaminergic and non‐dopaminergic neurones, respectively.
3
Addition of dopamine (10 μm) and quinpirole (1–100 μm) to the bath hyperpolarized the membrane of the type I neurones concomitantly with an increase in membrane conductance and an inhibition of action potentials which occurred spontaneously and were elicited by depolarizing pulses applied to the cell. However, quinpirole (10 μm) had no effect on the threshold for action potentials induced by a depolarizing pulse.
4
These quinpirole (10 μm)‐induced effects were antagonized by simultaneous application of domperidone (5 μm), a D2 receptor antagonist.
5
The amplitude of quinpirole (10 μm)‐induced hyperpolarization was decreased by increasing the potassium concentration in the perfusing fluid or simultaneous application of tetraethylammonium (10 μm).
6
SKF 38393 (10 or 100 μm), a D1 receptor agonist, had no effect on the resting membrane potential or action potential firing induced by a depolarizing pulse applied to the cell. However, when SKF 38393 (10 μm) was applied simultaneously with quinpirole (10 μm), the threshold for action potential generation was elevated by 5–6 mV, although there was no enhancement of hyperpolarization induced by quinpirole.
7
The elevation of the threshold for action potentials induced by SKF 38393 in the presence of quinpirole was antagonized by simultaneous application of SCH 23390 (5 μm), a D1 receptor antagonist.
8
Dopamine (10 μm), quinpirole (10 or 100 μm) and SKF 38393 (10 or 100 μm) had no effect on the resting membrane potential or spontaneously occurring action potentials in type II neurones.
9
These findings suggest that activation of dopamine D2 receptors of dopaminergic neurones in the VTA increases potassium conductance, thereby hyperpolarizing the membrane and eventually inhibiting neuronal activities. They also suggest that simultaneous activation of both D1 and D2 receptors enhances the D2 receptor‐mediated inhibitory effects by elevation of the threshold for action potential generation.
1
A microiontophoretic study was performed on chloral hydrate‐anaesthetized rats to examine the role of D1 receptors in the ventral tegmental area (VTA) neurones, which are inhibited by autoreceptor ...and D2 receptor agonists.
2
Inhibition by microiontophoretic application of quinpirole (a D2 agonist) of antidromic spikes elicited by stimulation of the nucleus accumbens in dopaminergic neurones of the VTA, was significantly enhanced by simultaneous application of SKF 38393 (D1 agonist), although SKF 38393 alone had little effect on the neurones.
3
In addition, quinpirole‐induced inhibition was antagonized by iontophoretic application of domperidone (D2 antagonist), but was not affected by SCH 23390 (D1 antagonist).
4
Furthermore, SKF 38393‐induced enhancement of inhibition by quinpirole was antagonized by simultaneous application of SCH 23390.
5
These results suggest that activation of D1 receptors located on the VTA dopaminergic neurones or on non‐dopaminergic nerve terminals is not essential for inducing inhibition of the dopaminergic neurones, but enhances D2 receptor‐mediated inhibition directly or indirectly via inhibitory neurones.
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