No abstract

Neurovascular coupling (NVC) is mediated via nitric oxide signalling, which is independently influenced by sex hormones and exercise training. Whether exercise training differentially modifies NVC pre- vs. post-puberty, where levels of circulating sex hormones will differ greatly within- and between-sexes, remains to be determined. Therefore, we investigated the influence of exercise training-status on resting intra-cranial haemodynamics and NVC at different stages of maturation. Posterior and middle cerebral artery velocities (PCAv and MCAv) and pulsatility index (PCAPI and MCAPI) were assessed via trans-cranial Doppler ultrasound at rest and during visual NVC stimuli. N=121 exercise-trained (males: n=32, females: n=32) and untrained (males: n=28, females: n=29) participants were characterised as pre- (males: n=33, females: n=29) or post- (males: n=27, females: n=32) peak height velocity (PHV). Exercise-trained youth demonstrated higher resting MCAv ( P=0.010). Maturity- and training-status did not affect the ∆PCAv and ∆MCAv during NVC. However, pre-PHV untrained males (19.4±13.5 vs. 6.8±6.0%; P≤0.001) and females (19.3±10.8 vs. 6.4±7.1%; P≤0.001) had a higher ∆PCAPI during NVC than post-PHV untrained counterparts, while the ∆PCAPI was similar in pre- and post-PHV trained youth. Pre-PHV untrained males (19.4±13.5 vs. 7.9±6.0%; P≤0.001) and females (19.3±10.8 vs 11.1±7.3%; P=0.016) also had a larger ∆PCAPI than their pre-PHV trained counterparts during NVC, but the ∆PCAPI was similar in trained and untrained post-PHV youth. Collectively, our data indicate that exercise training elevates regional cerebral blood velocities during youth, but training-mediated adaptations in NVC are only attainable during early stages of adolescence. Therefore, childhood provides a unique opportunity for exercise-mediated adaptations in NVC.

Behavioral and pharmacological testing in mice has been revamped following the development of new tools for the manipulation of genetic information. We present the results from the peak procedure, an operant test that assesses the capacity to perceive, remember, and act upon temporal information. We studied the basic timing abilities in two different strains of mice, the C57Bl/6J and C3H/HeJ, and their response to psychoactive substances. Scopolamine and high doses of d-amphetamine disrupted performance by increasing response variability. The effect of d-amphetamine was particularly clear in C3H mice. Whereas scopolamine did not seem to affect the location of the response, the effect of a low dose of d-amphetamine, a leftward shift, was consistent with the hypothesis that it accelerates the internal time keeping mechanism. Physostigmine alone improved performance by reducing variability between trials without affecting the response location. Pretreatment with physostigmine partially blocked the deleterious effects of scopolamine. Methylphenidate did not have major effects on timing behavior in C57 but in the highest dose shifted the response of C3H mice to the left. The higher sensitivity of the C3H strain to the effects of d-amphetamine and methylphenidate support its value as an animal model of attention deficit disorder. The performance of mice in this temporal task was comparable to that observed in rats and pigeons, and seemed exquisitely sensitive to pharmacological manipulation. *Mauricio R. Papini was the action editor for this paper.We are thankful to Gustavo Stolovitzky for the development of the software used for the start-stop analysis, to John Wearden for generously sharing unpublished data, to Warren Meck, Aya Sasaki and two anonymous reviewers for useful comments on an earlier version of this manuscript.

Apnea (breath-holding) elicits co-activation of sympathetic and parasympathetic nervous systems, affecting cardiac control. In situations of autonomic co-activation (e.g., cold water immersion), cardiac arrhythmias are observed during apnea. Chronic endurance training reduces resting heart rate in part via elevation in parasympathetic tone, and has been identified as a risk factor for development of arrhythmias. However, few studies have investigated autonomic control of the heart in trained athletes during stress. Therefore, we determined whether heightened vagal tone resulting from endurance training promotes a higher incidence of arrhythmia during apnea. We assessed the heart rate, rhythm (ECG lead II), and cardiac inotropic (speckle-tracking echocardiography) response to apnea in 10 endurance trained and 7 untrained participants. Participants performed an apnea at rest and following sympathetic activation using post-exercise circulatory occlusion (PECO). All apneas were performed prior to (CON) and following vagal block using glycopyrrolate (GLY). Trained participants had lower heart rates at rest (p=0.03) and during apneas (p=0.009) under CON. At rest, 3 trained participants exhibited instances of junctional rhythm and 4 trained participants developed ectopy during CON apneas, whereas 3 untrained participants developed ectopic beats only with concurrent sympathetic activation (PECO). Following GLY, no arrhythmias were noted in either group. Vagal block also revealed increased cardiac chronotropy (heart rate) and inotropy (strain rate) during apnea, demonstrating a greater sympathetic influence in the absence of parasympathetic drive. Our results highlight that endurance athletes may be more susceptible to ectopy via elevated vagal tone, whereas untrained participants may only develop ectopy through autonomic conflict.