Of roughly 140 miRNA expressed in five regions of the rat brain (cortex, hippocampus,
cerebellum, brainstem, and olfactory bulb), the majority (79%–97%) were also found in synaptosomes from each region (Figure 2D). While a significant number (up to ∼25%) of the miRNA detected in the study showed region specificity, the fact that about 100 of the detected miRNA were found in all regions suggests that most miRNA are part of core neural machinery. Interestingly, a small subset of miRNA was exclusively detected in synaptic material in each region (3%–9%), implying dedicated synaptic functions. When a subset of the synaptic miRNA was then quantified after kainic acid-induced seizure, the majority (five out of six) showed www.selleckchem.com/products/BMS-777607.html a significant activity-dependent change in the synaptic find more material even though changes in whole tissue were often not detected (Pichardo-Casas et al., 2012). Of particular interest, several of these activity-dependent miRNA displayed strikingly different changes in different brain regions; for example, miR-150 is increased over 5-fold in cortical synaptosomes but is reduced about the same fold in hippocampus, whereas miR-125 displays the opposite trend. Although this comparative analysis has only been applied to a handful of synaptic miRNA, it suggests that future functional analysis may reveal many new synaptic functions for miRNA
and that there may be dramatic specificity Megestrol Acetate in these functions in different neural circuits. If miRNA expression, localization, or function can be controlled by neural activity or other influences of neighboring cells and the environment, then miRNA can serve as agents of adaptive state change. Sensory input to the nervous system from the environment appears to trigger significant
changes in miRNA stability in the visual system (e.g., Krol et al., 2010). Moreover, from a developmental perspective, a substantial body of evidence shows that miRNA production and activity is controlled by several canonical cell-signaling pathways known to be important for many stages in the construction of neural circuits (reviewed by Saj and Lai, 2011). In addition to hardwiring neural circuits, some of these pathways are also known to link synaptic form and function to neural activity (e.g., brain-derived neurotrophic factor [BDNF]; Schratt et al., 2006). Multiple studies have surveyed miRNA levels in models of activity-dependent synapse plasticity (reviewed by Olde Loohuis et al., 2012). For example, in hippocampal slices subjected to long-term potentiation (LTP) or depression of synaptic output, the majority of detected miRNA (55 of 62) showed more than 2-fold up- or downregulation (Park and Tang, 2009). The temporal dimension adds another layer of complexity in the adaptive response.