Rodent models produce data which underpin biomedical research and non-clinical drug trials, but translation from rodents into successful clinical outcomes is often lacking. There is a growing body of evidence showing that improving experimental design is key to improving the predictive nature of rodent studies and reducing the number of animals used in research. Age, one important factor in experimental design, is often poorly reported and can be overlooked. The authors conducted a survey to assess the age used for a range of models, and the reasoning for age choice. From 297 respondents providing 611 responses, researchers reported using rodents most often in the 6–20 week age range regardless of the biology being studied. The age referred to as ‘adult’ by respondents varied between six and 20 weeks. Practical reasons for the choice of rodent age were frequently given, with increased cost associated with using older animals and maintenance of historical data comparability being two important limiting factors. These results highlight that choice of age is inconsistent across the research community and often not based on the development or cellular ageing of the system being studied. This could potentially result in decreased scientific validity and increased experimental variability. In some cases the use of older animals may be beneficial. Increased scientific rigour in the choice of the age of rodent may increase the translation of rodent models to humans.

Neuromodulation plays important and stage‐dependent roles in regulating locomotor central pattern (CPG) outputs during vertebrate motor system development. Dopamine, serotonin and nitric oxide are three neuromodulators that potently influence CPG outputs in the development of Xenopus frog tadpole locomotion. However, their roles switch from predominantly inhibitory early in development to mainly excitatory at later stages. In this review, we compare the stage‐dependent switching in neuromodulation in Xenopus with other vertebrate systems, notably the mouse and the zebrafish, and highlight features that appear to be phylogenetically conserved.

Reactive oxygen and nitrogen species (ROS/RNS) have been widely implicated in the ageingThe free radical theory of ageing is one of the most prominent theories to explain the ageing process (Harman, 1956). This theory postulates that ageing and age-related diseases arise as a result of cumulative changes and/or damage to cells and tissues inflicted by reactive species. Under normal physiological conditions, redox homeostasis establishes a dynamic balance between pro-oxidants and antioxidants whereby the production of reactive species are scavenged by antioxidants to minimise damage. However, with increasing age, studies have shown that the pro-oxidantantioxidant balance is compromised with a shift to the former resulting in an increase in reactive species. This imbalance induces oxidative stress, a state where endogenous antioxidant defense systems are overwhelmed leading to oxidative damage. More recent advances of this theory have shown that while, in laboratory reared animals, oxidative damage does not appear to affect lifespan it certainly increases oxidative damage and can contribute to age-related pathology (Salmon et

Dynamic neuronal Na + /K + pumps normally only respond to intense action potential firing owing to their low affinity for intracellular Na + . Recruitment of these Na + pumps produces a post-activity ultraslow afterhyperpolarization (usAHP) up to $10 mV in amplitude and $60 s in duration, which influences neuronal properties and future network output. In spinal motor networks, the usAHP underlies short-term motor memory (STMM), reducing the intensity and duration of locomotor network output in a manner dependent on the interval between locomotor bouts. In contrast to tonically active Na + pumps that help set and maintain the resting membrane potential, dynamic Na + pumps are selectively antagonized by low concentrations of ouabain, which, we show, blocks both the usAHP and STMM. We examined whether dynamic Na + pumps and STMM can be influenced by neuromodulators, focusing on 5-HT and nitric oxide. Bath-applied 5-HT alone had no significant effect on the usAHP or STMM. However, this is due to the simultaneous activation of two distinct 5-HT receptor subtypes (5-HT7 and 5-HT2a) that have opposing facilitatory and suppressive influences, respectively, on these two features of the locomotor system. Nitric oxide modulation exerts a potent inhibitory effect that can completely block the usAHP and erase STMM. Using selective blockers of 5-HT7 and 5-HT2a receptors and a nitric oxide scavenger, PTIO, we further provide evidence that the two modulators constitute an endogenous control system that determines how the spinal network self-regulates the intensity of locomotor output in light of recent past experience.

Major depressive disorder (MDD) in older people is a relatively common, yet hard to treat problem. In this study, we aimed to establish if a single nucleotide polymorphism in the 5-HT receptor gene (rs6295) determines antidepressant response in patients aged > 80 years (the oldest old) with MDD. Nineteen patients aged at least 80 years with a new diagnosis of MDD were monitored for response to citalopram 20 mg daily over 4 weeks and genotyped for the rs6295 allele. Both a frequentist and Bayesian analysis was performed on the data. Bayesian analysis answered the clinically relevant question: 'What is the probability that an older patient would enter remission after commencing selective serotonin reuptake inhibitor (SSRI) treatment, conditional on their rs6295 genotype?' Individuals with a CC (cytosine-cytosine) genotype showed a significant improvement in their Geriatric Depression Score ( = 0.020) and cognition ( = 0.035) compared with other genotypes. From a Bayesian perspective, we updated reports of antidepressant efficacy in older people with our data and calculated that the 4-week relative risk of entering remission, given a CC genotype, is 1.9 [95% highest-density interval (HDI) 0.7-3.5], compared with 0.52 (95% HDI 0.1-1.0) for the CG (cytosine-guanine) genotype. The sample size of = 19 is too small to draw any firm conclusions, however, the data suggest a trend indicative of a relationship between the rs6295 genotype and response to citalopram in older patients, which requires further investigation.