The role of post-synaptic neurones in the biochemical maturation of presynaptic cholinergic nerve terminals in a mouse sympathetic ganglion

1. The role of post-synaptic adrenergic neurones in the biochemical maturation of presynaptic cholinergic nerve terminals has been investigated in mouse superior cervical ganglion in vivo.2. Selective destruction of ganglion adrenergic neurones chemically, with 6-hydroxydopamine (6-OH-DA), or immunologically, with nerve growth factor antiserum (NGF-antiserum) prevented the normal maturation of choline acetyl transferase (ChAc) activity in presynaptic endings during development. Enzyme activity remained depressed for at least 2 months.3. 6-OH-DA treatment failed to alter ChAc activity in the developing duodenum or diaphragm, organs in which cholinergic fibres do not synapse with adrenergic neurones, suggesting that destruction of post-synaptic neurones per se inhibited presynaptic maturation.4. Similarly, NGF-antiserum, which does not destroy adrenergic neurones in the adult did not alter ChAc activity in adult mouse ganglia.5. These observations suggest that post-synaptic adrenergic neurones regulate the biochemical development of presynaptic cholinergic nerve terminals.     

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.     

A transient acidification linked to intracellular Ca2+ in anti-mu-stimulated human B-lymphocytes.

Mitogen-induced cellular proliferation is in many cell types preceded by rapid changes in intracellular pH and free Ca2+ concentration. We studied the patterns of pH and Ca2+ changes in normal resting human B-lymphocytes after exposure to anti-mu antibodies and the monoclonal antibody IF5, reactive with the CD20 antigen, both able to activate resting B-lymphocytes to enter the G1 phase of the cell cycle. Monitoring intracellular pH with the pH-sensitive, fluorescent dye, 2',7'-bis(carboxyethyl)-5,6-carboxy-fluorescein, we demonstrated that poly- and monoclonal anti-mu antibodies induced a rapid (maximum change within 2 min) intracellular acidification of 0.06 pH units followed by a slower (10-15 min) alkalinization towards, or slightly above, the resting pH of 6.88. The acidification response was amiloride-resistant, whereas the return to baseline was sensitive. Intracellular free Ca2+ was measured by using the fluorescent Ca2+ dye, indo-I. Exposure of cells to anti-mu resulted in a rapid increase (maximum change within 2 min) in cytoplasmic Ca2+ of 340 nM and a slower decline in fluorescence back to baseline of about 180 nM. In contrast to anti-mu, IF5 caused no change in cytoplasmic Ca2+ and pH. However, the Ca2+ ionophore ionomycin at low concentrations mimicked the Ca2+ response as well as the pH response to anti-mu. In Ca2(+)-free solutions the intracellular Ca2+ stores are usually rapidly depleted and, indeed, the Ca2+ and pH responses to anti-mu were reduced after 5 min and almost abolished after 35 min under such conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

EEG-Monitored ECT: A Comparison of Seizure Duration under Anesthesia with Etomidate and Thiopentone

Electroencephalogram-monitored electroconvulsive therapy (ECT) was carried out in 20 depressed inpatients. Before treatment, patients were randomly allocated to treatment using etomidate (Hypnomidat) (n = 10) or thiopentone (n = 10) for anesthesia. The groups were matched for sex, age, weight, and type and severity of depression. The seizure duration (seconds) was measured by electroencephalography (EEG), and the electrical energy (Joules, J) was determined for each treatment. A ratio of seizure duration:electrical energy (s/J) was computed. Both seizure duration and seizure duration:electrical energy were greater in the etomidate group than in the thiopentone group, whereas electrical energy did not differ significantly. The number of treatments in the etomidate group did not differ from that in the thiopentone group, as may be expected, perhaps because of the small size.     

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract.
2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME 30 mg kg⁻¹). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions.
4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

     

Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

Endothelin-1 and nitric oxide play an important regulatory role in the control of vascular smooth muscle tone. Nitroglycerin (NTG), a nitric oxide donating drug, may inhibit endothelin production. In this double-blind placebo-controlled crossover study, plasma levels of endothelin-1 were measured before and immediately (5–30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 g·kg^–1·min^–1, or placebo (isotonic saline) was infused successively for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats·min^–1. No changes in endothelin-1 plasma levels were induced by NTG infusion (2.4 pg·ml^–1 before NTG vs. 2.7 pg·ml^–1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion.     

Response amplification in sensory-specific cortices during crossmodal binding

Integrating information across the senses can enhance our ability to detect and classify stimuli in the environment. For example, auditory speech perception is substantially improved when the speaker's face is visible. In an fMRI study designed to investigate the neural mechanisms underlying these crossmodal behavioural gains, bimodal (audio-visual) speech was contrasted against both unimodal (auditory and visual) components. Significant response enhancements in auditory (BA 41/42) and visual (V5) cortices were detected during bimodal stimulation. This effect was found to be specific to semantically congruent crossmodal inputs. These data suggest that the perceptual improvements effected by synthesizing matched multisensory inputs are realised by reciprocal amplification of the signal intensity in participating unimodal cortices.