Mental and physical skill training increases neurogenesis via cell survival in the adolescent hippocampus.

The adolescent hippocampus produces thousands more new neurons daily than the adult, yet many die within weeks of their generation (Cameron and McCay, 2001; Curlik, DiFeo & Shors, 2014; Shors et al., 2016). Learning new skills can increase their survival. The present study tested the effects of physical skill training on the survival of these newly generated cells in males and female rodents during puberty. Newly generated cells were labeled with BrdU, a marker of cell mitosis, and training began one week later, just as the new cells begin to die. Significantly more BrdU-labeled cells were present in the hippocampus of both sexes after engaging in the physical training experiences. The young animals were able to maintain their balance on a modified rotarod task throughout most trials of training and as a consequence expended considerable energy and endurance during each training trial. These data suggest that a combination of both exercise and skill training can increase brain plasticity through increases in neurogenesis in the adolescent hippocampus. This finding supports the premise behind a clinical intervention known as MAP Training, which combines mental and physical training to enhance brain health in humans (Shors et al., 2014; Alderman et al., 2016). Although theoretical at this stage, the positive consequences of MAP Training for brain function may be mediated through neurogenesis. This article is part of a Special Issue entitled SI: Adolescent plasticity.

Sexual Conspecific Aggressive Response (SCAR): A Model of Sexual Trauma that Disrupts Maternal Learning and Plasticity in the Female Brain.

Sexual aggression can disrupt processes related to learning as females emerge from puberty into young adulthood. To model these experiences in laboratory studies, we developed SCAR, which stands for Sexual Conspecific Aggressive Response. During puberty, a rodent female is paired daily for 30-min with a sexually-experienced adult male. During the SCAR experience, the male tracks the anogenital region of the female as she escapes from pins. Concentrations of the stress hormone corticosterone were significantly elevated during and after the experience. Moreover, females that were exposed to the adult male throughout puberty did not perform well during training with an associative learning task nor did they learn well to express maternal behaviors during maternal sensitization. Most females that were exposed to the adult male did not learn to care for offspring over the course of 17 days. Finally, females that did not express maternal behaviors retained fewer newly-generated cells in their hippocampus whereas those that did express maternal behaviors retained more cells, most of which would differentiate into neurons within weeks. Together these data support SCAR as a useful laboratory model for studying the potential consequences of sexual aggression and trauma for the female brain during puberty and young adulthood.

The motirod: a novel physical skill task that enhances motivation to learn and thereby increases neurogenesis especially in the female hippocampus.

Males and females perform differently on a variety of training tasks. In the present study we examined performance of male and female rats while they were trained with a gross motor skill in which they learn to maintain their balance on an accelerating rotating rod (the accelerating rotarod). During training, many animals simply step off the rod, thus terminating the training. This problem was addressed by placing cold water below the rod. We termed the new training procedure "motirod" training because the trained animals were apparently motivated to remain on the rod for longer periods of time. Groups of male and female adult Sprague-Dawley rats were trained on either the standard accelerating rotarod or the motirod for four trials per day on four consecutive days. Latency to fall from the rod (in seconds) was recorded. The motivating feature increased performance especially in females (p=.001). As a consequence of enhanced performance, females retained significantly more new cells in the dentate gyrus of the hippocampus than those trained on the accelerating rotarod or those that received no training. In addition, individuals that learned well retained more new cells, irrespective of sex or task conditions. Previous studies have established that new cells rescued from death by learning remain in the hippocampus for months and mature into neurons (Leuner et al., 2004a; Shors, 2014). These data suggest that sex differences in physical skill learning can arise from sex differences in motivation, which thereby influence how many new neurons survive in the adult brain. This article is part of a Special Issue entitled SI: Brain and Memory.

Preparing for adulthood: thousands upon thousands of new cells are born in the hippocampus during puberty, and most survive with effortful learning.

The dentate gyrus of the hippocampal formation generates new granule neurons throughout life. The number of neurons produced each day is inversely related to age, with thousands more produced during puberty than during adulthood, and many fewer produced during senescence. In adulthood, approximately half of these cells undergo apoptosis shortly after they are generated. Most of these cells can be rescued from death by effortful and successful learning experiences (Gould et al., 1999; Waddell and Shors, 2008; Curlik and Shors, 2011). Once rescued, the newly-generated cells differentiate into neurons, and remain in the hippocampus for at least several months (Leuner et al., 2004). Here, we report that many new hippocampal cells also undergo cell death during puberty. Because the juvenile brain is more plastic than during adulthood, and because many experiences are new, we hypothesized that a great number of cells would be rescued by learning during puberty. Indeed, adolescent rats that successfully acquired the trace eyeblink response retained thousands more cells than animals that were not trained, and those that failed to learn. Because the hippocampus generates thousands more cells during puberty than during adulthood, these results support the idea that the adolescent brain is especially responsive to learning. This enhanced response can have significant consequences for the functional integrity of the hippocampus. Such a massive increase in cell proliferation is likely an adaptive response as the young animal must emerge from the care of its mother to face the dangers, challenges, and opportunities of adulthood.