Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High- frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.      

Adaptive coping strategies in patients with chronic pain conditions and their interpretation of disease

Background  

We examined which adaptive coping strategies, referring to the concept of 'locus of disease control', were of relevance for patients with chronic pain conditions, and how they were interconnected with patients' life satisfaction and interpretation of disease.     

Parental mosaicism and autosomal dominant mutations causing structural abnormalities of collagen I are frequent in families with osteogenesis imperfecta type III/IV

Abstract Protein-chemical and molecular studies were conducted on all osteogenesis imperfecta (OI) type III/IV patients referred to our hospital during the last 15 y. Of a total of 16 OI type III/IV patients studied, 15 patients were heterozygous for a mutation in one of the two genes coding for collagen I, COL1A1 or COL1A2. Cultured fibroblasts from these 15 patients produced both normal and abnormal collagen I molecules, pointing to a dominant-negative effect of the mutation. Nine mutations had not been described previously. Parental mosaicism was demonstrated in three families. In the 16th child the causative mutation was not found. In conclusion, OI type III/IV in most patients of Western European ancestry is caused by dominant mutations in the genes for collagen I, and recurrence of OI is caused in most cases by parental gonadal mosaicism.     

Neonatal hearing screening with an automated auditory brainstem response screener in the infant's home

Universal neonatal hearing screening is essential if all infants with congenital or perinatally acquired hearing impairment are to begin treatment before the age of 6 months to facilitate development of speech, language, communication and academic skills. Screening cannot always take place in hospital because of the increase in very short-stay deliveries. Therefore screening in the home may be necessary to achieve a high level of screening. We describe a feasibility study with an automated auditory brainstem response (AABR) screener in the infant's home as part of the service offered by the Well Baby Clinics in the Netherlands. Of the 277 infants who completed the screening 266 had the result "pass", 7 "refer" and 4 had inconclusive results. The mean time needed per screening was 18 min. This study shows that neonatal hearing screening by nurses using an AABR infant screener in the home is feasible.     

Prospective evaluation of posttransfusion hepatitis

The incidence of posttransfusion hepatitis (PTH) was determined prospectively at our institution. An active surveillance program of transfused surgical patients was set up; alanine aminotransferase (ALT) levels were determined before transfusion and at monthly intervals for 6 months after transfusion. Patients with confirmed ALT values greater than 2.5 times the upper reference values were referred to the out-patient clinics for diagnosis. Of 4051 surgical patients who underwent transfusion between January 1986 and December 1989, 2459 (60.7%) were enrolled in the surveillance program, and 1018 (25.1%) completed the follow-up; 238 patients received autologous blood only and were used as controls. No PTH was observed in the control patients, and the incidence of the disease in patients receiving homologous blood was 10.97 percent in 1986, 6.58 percent in 1987, 5.55 percent in 1988, and 4.29 percent in 1989; the decreasing trend is significant (p = 0.018).