Air Pollution Role as Risk Factor of Cardioinhibitory Carotid Hypersensitivity

Little is known about the impact of air pollution on neuroautonomic system. The authors have investigated possible influence of air pollution and outdoor temperature on the carotid sinus hypersensitivity (CSH), as main cause of neurally mediated syncope in forty-years-old subjects and older. Pollutants’ concentrations and outdoor temperature of days in which 179 subjects with recurrent syncope underwent carotid sinus massage (CSM) were analyzed. Before this manoeuvre, cardiovascular control by short period heart and blood pressure spectral duration of segment between the end of P and R ECG-waves (PeR) were registred; RR variability on the same short period ECG recordings and their spectral coherence were also analyzed. CSH was found in 57 patients (28 with cardioinhibitory response and 29 subjects showed vasodepressor reaction), while 122 subjects had a normal response. CSM performed during high ozone concentrations was associated with slightly higher risk of cardioinhibitory response (odd ratio 1.012, 95% CI 1.001–1.023, p < 0.05), but neither this or other polluting agent nor outdoor temperature seemed to influence autonomic control in basal resting condition. Thus, ozone seemed to influence response to the CSM in CSH patients and it is probably able to facilitate a cardioinhibitory response, perhaps through an increase of nerve acetylcholine release. P→PR coherence could be useful in predicting a sinus cardioinhibitory hypersensitivity in those cases when CSM is contraindicated.

Directed motor actions and choice signalling drive cortical acetylcholine dynamics.

Numerous cognitive functions including attention, learning, and plasticity are influenced by the dynamic patterns of acetylcholine release across the brain. How acetylcholine mediates these functions in cortex remains unclear, as the spatiotemporal relationship between cortical acetylcholine and behavioral events has not been precisely measured across task learning. To dissect this relationship, we quantified motor behavior and sub-second acetylcholine dynamics in primary somatosensory cortex during acquisition and performance of a tactile-guided object localization task. We found that acetylcholine dynamics were spatially homogenous and directly attributable to whisker motion and licking, rather than sensory cues or reward delivery. As task performance improved across training, acetylcholine release to the first lick in a trial became dramatically and specifically potentiated, paralleling the emergence of a choice-signalling basis for this motor action. These results show that acetylcholine dynamics in sensory cortex are driven by directed motor actions to gather information and act upon it.

Cholinergic deficits selectively boost cortical intratelencephalic control of the striatum in Huntington’s disease

Huntington’s disease (HD) is a progressive, neurodegenerative disease caused by a CAG triplet expansion in the huntingtin gene. Although corticostriatal dysfunction has long been implicated in HD, the determinants and pathway specificity of this pathophysiology remain a matter of speculation. To help fill this gap, the zQ175+/- knockin mouse model of HD was studied using approaches that allowed optogenetic interrogation of intratelencephalic (IT) and pyramidal tract (PT) connections with principal striatal spiny projection neurons (SPNs). These studies revealed that the connectivity of IT, but not PT, neurons with direct and indirect pathway SPNs increased in early symptomatic zQ175+/- HD mice. This enhancement was attributable to reduced inhibitory control of IT terminals by striatal cholinergic interneurons (ChIs). Lowering mutant huntingtin selectively in ChIs with a virally-delivered zinc finger repressor protein normalized striatal acetylcholine release and IT functional connectivity – revealing a novel node in the network underlying corticostriatal pathophysiology in HD.

Botox or the new face of the fight against depression - literature review

Introduction: Depression is a common psychiatric disorder leading to high burden especially for some other psychiatric comorbidity. Annually over 43 billion dollars are expended for patients with depression among them 28% are directly for depression and other costs are related to mortality and morbidity due to depression. The aim of the study: Paying attention to new options for treating depression – a disease that affects more and more people.Material and method: The research was done by the usage of the PubMed and Google Scholar articles about the topic of: botulinum toxin; depression; treatment.Description of the state of knowledge: Injecting Botox into the muscles responsible for expression of anguish or sadness may potentially decrease the patients experience of feelings. Botox reversibly blocks acetylcholine release from neuronal axons into the synapse, inhibiting neuromuscular transmission. If the facial feedback hypothesis is correct, by injecting Botox into the corrugator and procerus muscles, it will reversibly inhibit frown facial expressions and have the capability of propagating or enhancing sad and depressed feelings.Summary: The results from all randomized control trials proved that botulinum toxin A injection in the glabellar region was associated with significant improvement mood and may be a safe and effective treatment to reduce symptoms of depression.

Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which was required to maintain responsivity to odors in untrained conditions. Downstream from the mushroom body, a set of MBONs that receive their input from the γ3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which discriminative effects influence appetitive memory and decision-making. These data demonstrate that learning drives valence correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.

Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction

Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.