Meglic, P. | bioRxiv Science

bioRxiv2024

MIROSLAV: A complete open-source hardware and software toolkit for high-throughput circadian activity measurement and analysis in rodents

While conventional behavioural tests offer valuable insight into rodent behaviour in specific paradigms, rodents spend most of their time in a safe, undisturbed environment - their home cage. However, home cage monitoring (HCM) is often impractical at scale over prolonged periods of time without significant loss of data. To achieve this, we developed MIROSLAV, the Multicage InfraRed Open Source Locomotor Activity eValuator, a home cage activity and environmental monitoring device designed to be open, adaptable, and robust. Its transparent and modular design allows the device to be tailored to varying experimental requirements and environmental conditions, while its wireless operation and multiple redundancies minimise loss of data and animal disturbance. Data quality is maintained by a modular software workflow for data preparation (Prepare-a-SLAV) and cleaning (TidySLAV), followed by exploratory (MIROSine - MIRO The Explorer) and statistical (MIROSine - StatistiSLAV) analysis of circadian periodicity. Here, using MIROSLAV, we demonstrate circadian dysrhythmia and a disrupted response to regular stimuli (e.g. behavioural testing, bedding change) in a rat model of sporadic Alzheimers disease, showcasing MIROSLAVs utility in a typical animal study of disease. In accordance with the 3Rs, every rodent study and laboratory performing them can benefit from HCM, provided the existence of transparent and customisable tools which allow robust deployment to tens or hundreds of cages in various conditions. MIROSLAV provides this opportunity to researchers in a cost-effective manner.

animal behavior and cognition↗

bioRxiv2024

Experimental parkinsonism induced by tetanus toxin injected into basal ganglia

Background and ObjectivesLocal inhibitory circuits and long-range inhibitory projections within the interconnected basal ganglia nuclei are critical for control of voluntary movement and pathophysiology of different extrapyramidal movement disorders. Herein, we examined the major motor effects of tetanus neurotoxin (TeNT), a presynaptic neurotoxin that selectively targets the GABA-ergic synaptic transmission, when injected into individual basal ganglia nuclei. MethodsThe rats were injected with low-dose TeNT (0.4-0.8 ng) unilaterally into globus pallidus internus (GPi), substantia nigra (SN), or caudate putamen (CPu). The effects of TeNT-induced disinhibition were characterized by repeated assessments of motor coordination, gait, and rotational behavior, followed by measurement of regional protein content of major neuronal monoaminergic, GABA-ergic and glutamatergic population markers. ResultsIn the beamwalk test, the CPu injection of TeNT induced contralateral plantar misplacement. TeNT injections into GPi and CPu were associated with decreased stride length and increased duration of step cycle and induced a slight ipsiversive circling during open field observation, and more intensive rotational behavior during swimming, differentially affected by D-amphetamine. Unlike rotational behavior, the gait and motor control deficits during beamwalk recovered promptly by day 14 post TeNT, which, along with the lack of reduced neuronal marker protein contents, suggested the reversibility and lack of neuronal degeneration. Conclusion and ImplicationsTetanus toxin injected into basal ganglia evokes transient hypokinetic motor dysfunctions consistent with experimental parkinsonism, with differential occurrence of individual motor symptoms depending on the region targeted. These results suggest that TeNT might be a useful non-neurodegenerative pharmacological agent for investigating the motor control abnormalities involving GABA-ergic basal ganglia circuits.

pharmacology and toxicology↗