Exploration biases how forelimb reaches to a spatial target are learned.

The brain can learn to generate actions, such as reaching to a target, using different movement strategies. Understanding how different variables bias which strategies are learned to produce such a reach is important for our understanding of the neural bases of movement. Here we introduce a novel spatial forelimb target task in which perched head-fixed mice learn to reach to a circular target area from a set start position using a joystick. These reaches can be achieved by learning to move into a specific direction or to a specific endpoint location. We find that mice gradually learn to successfully reach the covert target. With time, they refine their initially exploratory complex joystick trajectories into controlled targeted reaches. The execution of these controlled reaches depends on the sensorimotor cortex. Using a probe test with shifting start positions, we show that individual mice learned to use strategies biased to either direction or endpoint-based movements. The degree of endpoint learning bias was correlated with the spatial directional variability with which the workspace was explored early in training. Furthermore, we demonstrate that reinforcement learning model agents exhibit a similar correlation between directional variability during training and learned strategy. These results provide evidence that individual exploratory behavior during training biases the control strategies that mice use to perform forelimb covert target reaches.

Differential regulation of contractility and nitric oxide sensitivity in gravid and nongravid myometrium during late pregnancy in a marsupial.

Marsupials have two anatomically separate uteri; and in macropodids (kangaroos and wallabies), there is a single ovulation from alternate ovaries in each cycle. During late pregnancy, the two uteri are differentially regulated by local hormonal influences from the corpus luteum, the fetus, and placenta on one side and by the developing Graafian follicle on the other. In this study, we report striking differences in contractile behavior of nongravid and gravid myometrium from the tammar wallaby (Macropus eugenii) in late pregnancy and immediately post partum. Nongravid myometrium, from the uterus ipsilateral to a Graafian follicle, was spontaneously active but unresponsive to the oxytocic peptide mesotocin and the smooth muscle relaxant nitric oxide. Myometrium from the contralateral, gravid uterus, which contained a conceptus and was associated with an active corpus luteum, was not spontaneously active. Gravid myometrium became increasingly sensitive to mesotocin stimulation as pregnancy progressed, and nitric oxide induced marked relaxation at all stages examined, by a guanylyl-cyclase mediated pathway. These results provide further evidence that the two uteri of marsupials are under differential control, suggesting that local endocrine and paracrine influences, derived from the ovaries, the fetus, and placenta, can regulate concurrent but distinct physiological responses in the reproductive tracts of these mammals.

Cortisol in fetal fluids and the fetal adrenal at parturition in the tammar wallaby (Macropus eugenii).

Glucocorticoid hormones may play a critical role in initiating parturition in tammar wallabies. In this study, we investigated the concentration of cortisol in fetal fluids and cortisol production by fetal adrenals over the last 3 days of the 26-day pregnancy and within 24 h postpartum. The fetal adrenals almost doubled in size between Days 24 and 26 of pregnancy, and their cortisol content increased over 10-fold during this period, from 10 pg to over 100 pg per adrenal pair. After birth, neonatal adrenals continued to grow, but cortisol content fell dramatically to 20 pg. The prepartum increase in adrenal cortisol was reflected by a substantial rise in cortisol concentrations in yolk sac fluid, allantoic fluid, and fetal blood, which were below 10 ng/ml on Day 24 and rose to over 40 ng/ml by Day 26. Cortisol concentrations in neonatal blood decreased postpartum, mirroring decreased cortisol content in neonatal adrenals. Cortisol production by the fetal adrenal was stimulated in vitro by ACTH and prostaglandin E2, suggesting that the in vivo increase may be stimulated by release of ACTH from the fetal hypothalamic-pituitary axis and prostaglandin E2 from the placenta. These results indicate that increasing cortisol production by the fetal adrenal is a characteristic of late pregnancy in the tammar wallaby and support the suggestion that fetal cortisol may trigger the initiation of parturition in this marsupial species.