Mechanisms Involved in Nicotinic Acetylcholine Receptor-Induced Neurotransmitter Release from Sympathetic Nerve Terminals in the Mouse Vas Deferens

Prejunctional nicotinic acetylcholine receptors (nAChRs) amplify postganglionic sympathetic neurotransmission, and there are indications that intraterminal Ca2+ stores might be involved. However, the mechanisms by which nAChR activation stimulates neurotransmitter release at such junctions is unknown. Rapid local delivery (picospritzing) of the nAChR agonist epibatidine was combined with intracellular sharp microelectrode recording to monitor spontaneous and field-stimulation-evoked neurotransmitter release from sympathetic nerve terminals in the mouse isolated vas deferens. Locally applied epibatidine (1 µM) produced ‘epibatidine-induced depolarisations’ (EIDs) that were similar in shape to spontaneous excitatory junction potentials (SEJPs) and were abolished by nonselective nAChR antagonists and the purinergic desensitizing agonist α,β-methylene ATP. The amplitude distribution of EIDs was only slightly shifted towards lower amplitudes by the selective α7 nAChR antagonists α-bungarotoxin and methyllcaconitine, the voltage-gated Na+ channel blocker tetrodotoxin or by blocking voltage-gated Ca2+ channels with Cd2+. Lowering the extracellular Ca2+ concentration reduced the frequency of EIDs by 69%, but more surprisingly, the Ca2+-induced Ca2+ release blocker ryanodine greatly decreased the amplitude (by 41%) and the frequency of EIDs by 36%. Ryanodine had no effect on electrically-evoked neurotransmitter release, paired-pulse facilitation, SEJP frequency, SEJP amplitude or SEJP amplitude distribution. These results show that activation of non-α7 nAChRs on sympathetic postganglionic nerve terminals induces high-amplitude junctional potentials that are argued to represent multipacketed neurotransmitter release synchronized by intraterminal Ca2+-induced Ca2+ release, triggered by Ca2+ influx directly through the nAChR. This nAChR-induced neurotransmitter release can be targeted pharmacologically without affecting spontaneous or electrically-evoked neurotransmitter release

Behavioural Significance of Cerebellar Modules

A key organisational feature of the cerebellum is its division into a series of cerebellar modules. Each module is defined by its climbing input originating from a well-defined region of the inferior olive, which targets one or more longitudinal zones of Purkinje cells within the cerebellar cortex. In turn, Purkinje cells within each zone project to specific regions of the cerebellar and vestibular nuclei. While much is known about the neuronal wiring of individual cerebellar modules, their behavioural significance remains poorly understood. Here, we briefly review some recent data on the functional role of three different cerebellar modules: the vermal A module, the paravermal C2 module and the lateral D2 module. The available evidence suggests that these modules have some differences in function: the A module is concerned with balance and the postural base for voluntary movements, the C2 module is concerned more with limb control and the D2 module is involved in predicting target motion in visually guided movements. However, these are not likely to be the only functions of these modules and the A and C2 modules are also both concerned with eye and head movements, suggesting that individual cerebellar modules do not necessarily have distinct functions in motor control

Genetic Basis of Myocarditis: Myth or Reality?

n/

Long-Term Follow-Up After Non-operative Management of Blunt Splenic and Liver Injuries: A Questionnaire-Based Survey

BACKGROUND Non-operative management (NOM) of blunt splenic or liver injuries (solid organ injury, SOI) has become the standard of care in hemodynamically stable patients. However, the incidence of long-term symptoms in these patients is currently not known. The aim of this study was to assess long-term symptoms in patients undergoing successful NOM (sNOM) for SOI. METHODS Long-term posttraumatic outcomes including chronic abdominal pain, irregular bowel movements, and recurrent infections were assessed using a specifically designed questionnaire and analyzed by univariable analysis. RESULTS Eighty out of 138 (58%) patients with SOI undergoing sNOM) responded to the questionnaire. Median (IQR) follow-up time was 48.8 (28) months. Twenty-seven (34%) patients complained of at least one of the following symptoms: 17 (53%) chronic abdominal pain, 13 (41%) irregular bowel movements, and 8 (25%) recurrent infections. One female patient reported secondary infertility. No significant association between the above-mentioned symptoms and the Injury Severity Score, amount of hemoperitoneum, or high-grade SOI was found. Patients with chronic pain were significantly younger than asymptomatic patients (32.1 ± 14.5 vs. 48.3 ± 19.4 years, p = 0.002). Irregular bowel movements were significantly more frequent in patients with severe pelvic fractures (15.4 vs. 0.0%, p = 0.025). A trend toward a higher frequency of recurrent infections was found in patients with splenic injuries (15.9 vs. 2.8%, p = 0.067). CONCLUSION A third of patients with blunt SOI undergoing sNOM reported long-term abdominal symptoms. Younger age was associated with chronic abdominal symptoms. More studies are warranted to investigate long-term outcomes immunologic sequelae in patients after sNOM for SOI