The phase of low-frequency network activity in the auditory cortex captures changes in neural excitability, entrains to the temporal structure of natural sounds, and correlates with the perceptual performance in acoustic tasks. Although these observations suggest a causal link between network rhythms and perception, it remains unknown how precisely they affect the processes by which neural populations encode sounds. We addressed this question by analyzing neural responses in the auditory cortex of anesthetized rats using stimulus-response models. These models included a parametric dependence on the phase of local field potential rhythms in both stimulus-unrelated background activity and the stimulus-response transfer function. We found that phase-dependent models better reproduced the observed responses than static models, during both stimulation with a series of natural sounds and epochs of silence. This was attributable to two factors: (1) phase-dependent variations in background firing (most prominent for delta; 1-4 Hz); and (2) modulations of response gain that rhythmically amplify and attenuate the responses at specific phases of the rhythm (prominent for frequencies between 2 and 12 Hz). These results provide a quantitative characterization of how slow auditory cortical rhythms shape sound encoding and suggest a differential contribution of network activity at different timescales. In addition, they highlight a putative mechanism that may implement the selective amplification of appropriately timed sound tokens relative to the phase of rhythmic auditory cortex activity.Key words: delta rhythm; information coding; LNP models; network state; neural coding; receptive fields IntroductionAccumulating evidence suggests that low-frequency rhythms play an important role for hearing (Schroeder and Lakatos, 2009;Giraud and Poeppel, 2012; Leong and Goswami, 2014). Neuroimaging and intracranial recordings show that neural activity in the auditory cortex (A1) at frequencies below ϳ12 Hz entrains to the temporal structure of sounds and carries information about sound identity Szymanski et al., 2011;Simon, 2012, 2013; Ng et al., 2013), possibly because natural sounds contain important acoustic structures at these frequencies Doelling et al., 2014;Gross et al., 2013). Importantly, the degree of rhythmic entrainment correlates with perceptual intelligibility (Mesgarani and Chang, 2012; Doelling et al., 2014;Peelle et al., 2013), linking the timescales relevant for acoustic comprehension with those of neural activity (Rosen, 1992;Ghitza and Greenberg, 2009; Zion Golumbic et al., 2012). Based on these results, it has been hypothesized that slow rhythmic activity in the A1 reflects key mechanisms of sound encoding that have direct consequences for hearing (Giraud and Poeppel, 2012;Peelle and Davis, 2012;Strauß et al., 2014b).This raises the central question of how precisely rhythmic auditory cortical activity shapes sensory information processing. Electrophysiological recordings showed that slow rhythms reflect fluctuatio...

Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternative therapeutic target; however, drug discovery programmes focused on this G protein-coupled receptor (GPCR) have failed largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviours and hyper-locomotion. By mapping the upstream signalling pathways regulating these responses, we determine the importance of receptor phosphorylation-dependent signalling in driving clinically relevant outcomes and in controlling adverse effects including "epileptic-like" seizures. We conclude that M1 mAChR ligands that promote receptor-phosphorylation dependent signalling would protect against cholinergic-adverse effects in addition to driving beneficial responses such as learning and memory and anxiolytic behaviour relevant for the treatment of AD.

Adenotonsillectomy patients represent the biggest challenge in postoperative pain management of the head and neck surgeries evaluated. The low rates of pain, nausea, and vomiting reported in the days following surgery for the other procedures suggests that children can be cared for at home with simple analgesia. Discharge information and analgesia prescribing on discharge should be tailored to the operation performed.

Three-dimensional printing of a model of the airway of a small child aided planning of bronchial intubation and single-lung ventilation. Three-dimensional printing of airway structures may have wider application in anaesthesia practice.

Pain management was inadequate in most of the groups studied, particularly after appendicectomy or umbilical hernia repair, with most children experiencing at least moderate pain on the day of and day after surgery. There was a need for a standardized management, with increased dual analgesia prescribing, to ensure that children receive adequate postoperative analgesia in hospital and at home.