Neural encoding of multiple motion speeds in visual cortical area MT.

Segmenting objects from each other and their background is critical for vision. The speed at which objects move provides a salient cue for segmentation. However, how the visual system represents and differentiates multiple speeds is largely unknown. Here we investigated the neural encoding of multiple speeds of overlapping stimuli in the primate visual cortex. We first characterized the perceptual capacity of human and monkey subjects to segment spatially overlapping stimuli moving at different speeds. We then determined how neurons in the motion-sensitive, middle-temporal (MT) cortex of macaque monkeys encode multiple speeds. We made a novel finding that the responses of MT neurons to two speeds of overlapping stimuli showed a robust bias toward the faster speed component when both speeds were slow (≤ 20°/s). The faster-speed bias occurred even when a neuron had a slow preferred speed and responded more strongly to the slower component than the faster component when presented alone. The faster-speed bias emerged very early in neuronal response and was robust over time and to manipulations of motion direction and attention. As the stimulus speed increased, the faster-speed bias changed to response averaging. Our finding can be explained by a modified divisive normalization model, in which the weights for the speed components are proportional to the responses of a population of neurons elicited by the individual speeds. Our results suggest that the neuron population, referred to as the weighting pool, includes neurons that have a broad range of speed preferences. As a result, the response weights for the speed components are determined by the stimulus speeds and invariant to the speed preferences of individual neurons. Our findings help to define the neural encoding rule of multiple stimuli and provide new insight into the underlying neural mechanisms. The faster-speed bias would benefit behavioral tasks such as figure-ground segregation if figural objects tend to move faster than the background in the natural environment.

Robust aversive effects of trace amine-associated receptor 1 activation in mice.

Drugs that stimulate the trace amine-associated receptor 1 (TAAR1) are under clinical investigation as treatments for several neuropsychiatric disorders. Previous studies in a genetic mouse model of voluntary methamphetamine intake identified TAAR1, expressed by the Taar1 gene, as a critical mediator of aversive methamphetamine effects. Methamphetamine is a TAAR1 agonist, but also has actions at monoamine transporters. Whether exclusive activation of TAAR1 has aversive effects was not known at the time we conducted our studies. Mice were tested for aversive effects of the selective TAAR1 agonist, RO5256390, using taste and place conditioning procedures. Hypothermic and locomotor effects were also examined, based on prior evidence of TAAR1 mediation. Male and female mice of several genetic models were used, including lines selectively bred for high and low methamphetamine drinking, a knock-in line in which a mutant form of Taar1 that codes for a non-functional TAAR1 was replaced by the reference Taar1 allele that codes for functional TAAR1, and their matched control line. RO5256390 had robust aversive, hypothermic and locomotor suppressing effects that were found only in mice with functional TAAR1. Knock-in of the reference Taar1 allele rescued these phenotypes in a genetic model that normally lacks TAAR1 function. Our study provides important data on TAAR1 function in aversive, locomotor, and thermoregulatory effects that are important to consider when developing TAAR1 agonists as therapeutic drugs. Because other drugs can have similar consequences, potential additive effects should be carefully considered as these treatment agents are being developed.

Depression-like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake.

Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression-like symptoms during early periods of withdrawal, compared with non-binge users. The impact of varying durations of MA abstinence on depression-like symptoms and on subsequent MA intake was examined in mice genetically prone to binge-level MA consumption. Binge-level MA intake was induced using a multiple-bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression-like symptoms were measured using a tail-suspension test and a subsequent forced-swim test, after forced abstinence of 6 and 30 hours from a 28-day course of chronic MA intake. An additional study measured the same depression-like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression-like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug-naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression-like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression-like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.