However, processes other than growth may contribute to changing cell size or number. For example, Buparlisib solubility dmso learning may enhance the survival of recently created new neurons (Zhao et al., 2008). Hence, it is possible that a decreased MD in the dentate gyrus reflects a slowing of the cell death process in the learning group while cell pruning continued at a higher rate in the control groups. The histological results provide important evidence about what cellular changes accompany the detected MRI effects, but they cannot directly demonstrate whether any or all of these particular cellular changes

drive the observed MD change. Future studies using pharmacological or genetic manipulations could test more directly the relationships between specific cellular changes and MRI effects. The rapid and perhaps transient nature of these learning-related changes provides a further challenge. In vivo methodologies will be useful to fully understand how neural tissue changes in the minutes and hours after learning. Thus, molecular and optical imaging are perhaps most suited to understand how these compartments change in the living organism. The present work, along with previous studies (Blumenfeld-Katzir et al., 2011 and Lerch et al., 2011) combining imaging and histology, provides valuable CH5424802 manufacturer insights into the types of structural

changes that can be detected on different timescales with noninvasive MRI. For instance, 5 days of training in the water maze task increased the volume of the hippocampus, as measured with MRI, and produced a correlated increase in GAP-43, a marker for neuronal process remodeling (Lerch et al., 2011). In another study using 5 days of training with the same task, changes in diffusion MRI parameters were related to increases in GFAP, synaptophysin, and myelin basic protein (MBP) (Blumenfeld-Katzir et al., 2011).

these The time frame of these studies allows for slower remodeling mechanisms like dendritric sprouting or gliogenesis to occur (Figure 1). Such mechanisms could contribute to the structural brain changes detected using MRI in humans with long-term learning (Draganski et al., 2004 and Scholz et al., 2009). Sagi and colleagues′ results provide us with an important reminder that the brain is an extremely dynamic structure. This study used a focused period of video game playing, but presumably many of the learning experiences we undergo throughout our lives produce similar effects in task-relevant regions of our brains. The findings therefore have more general implications for human neuroimaging. Many studies that employ the standard imaging methods used here assume that human brain structure is relatively static, at least on short timescales.