Corrigendum: Measuring Locomotor Activity and Behavioral Aspects of Rodents Living in the Home-Cage.

[This corrects the article DOI: 10.3389/fnbeh.2022.877323.].

Measuring Locomotor Activity and Behavioral Aspects of Rodents Living in the Home-Cage.

Automatization and technological advances have led to a larger number of methods and systems to monitor and measure locomotor activity and more specific behavior of a wide variety of animal species in various environmental conditions in laboratory settings. In rodents, the majority of these systems require the animals to be temporarily taken away from their home-cage into separate observation cage environments which requires manual handling and consequently evokes distress for the animal and may alter behavioral responses. An automated high-throughput approach can overcome this problem. Therefore, this review describes existing automated methods and technologies which enable the measurement of locomotor activity and behavioral aspects of rodents in their most meaningful and stress-free laboratory environment: the home-cage. In line with the Directive 2010/63/EU and the 3R principles (replacement, reduction, refinement), this review furthermore assesses their suitability and potential for group-housed conditions as a refinement strategy, highlighting their current technological and practical limitations. It covers electrical capacitance technology and radio-frequency identification (RFID), which focus mainly on voluntary locomotor activity in both single and multiple rodents, respectively. Infrared beams and force plates expand the detection beyond locomotor activity toward basic behavioral traits but discover their full potential in individually housed rodents only. Despite the great premises of these approaches in terms of behavioral pattern recognition, more sophisticated methods, such as (RFID-assisted) video tracking technology need to be applied to enable the automated analysis of advanced behavioral aspects of individual animals in social housing conditions.

Different affinities of inhibitors to the outwardly and inwardly directed substrate binding site of organic cation transporter 2.

The rat organic cation transporter 2 (rOCT2) was expressed in Xenopus laevis oocytes and cation-induced outward and inward currents were measured in whole cells and giant patches using voltage clamp techniques. Tetrabutylammonium (TBuA) and corticosterone were identified as nontransported inhibitors that bind to the substrate binding site of rOCT2. They inhibited cation-induced currents from both membrane sides. Increased substrate concentrations could partially overcome the inhibition. At 0 mV, the affinity of TBuA from the extracellular side compared with the intracellular side of the membrane was 4-fold higher, whereas the affinity of corticosterone was 20-fold lower. The data suggest that the substrate binding site of rOCT2 is like a pocket containing overlapping binding domains for ligands. These binding domains may undergo separate structural changes. From the extracellular surface, the affinity for uncharged corticosterone was increased by making membrane potential more negative. This implies potential-dependent structural changes in the extracellular binding pocket and existence of a voltage sensor. Interestingly, at 0 mV, an 18-fold higher affinity was determined for trans-inhibition of choline efflux by corticosterone compared with cis-inhibition of choline uptake. This suggests an additional high affinity-conformation of the empty outwardly oriented substrate binding pocket. A model is proposed that describes how substrates and inhibitors might interact with rOCT2. The data provide a theoretical basis to understand drug-drug interactions at polyspecific transporters for organic cations.