, 2011). For example, 19 such developmentally regulated miRNA in PFC were 24-fold more divergent in human than in chimpanzee. Thus, while gene regulatory pathways have long been proposed as a predominant driver of metazoan evolution (see Gerhart and Kirschner, 1997), miRNA may account for a significant part of

the expansion in cognitive and intellectual capacity in humans. Given the cellular and transcriptional complexity of the nervous system, it is not surprising that miRNAs are highly abundant in this tissue (reviewed by Duvelisib Kosik, 2006). Although initial comprehensive profiling of miRNA expression was limited to broad areas of the brain, the advent of new profiling technology makes it clear that the spatial landscape of miRNA expression may be highly complex at the cellular level. For example, by combining immunoprecipitation of tagged, transgenic Ago2 with the cell-type-specific Cre/Lox system in mouse (a method called “miRAP”; Figure 2A), it has been possible to ascertain the miRNA “finger prints” of different GABAergic interneurons and excitatory pyramidal cells from neocortex or Purkinje

cells from buy Bioactive Compound Library cerebellum (He et al., 2012). Nearly half of the over 500 miRNA assayed were relatively specific between overall neocortex and cerebellum, and roughly one-quarter of the miRNA showed specificity between pyramidal neurons and interneurons or between two subtypes of interneurons (parvalumin [PV] versus neuropeptide somatostatin expressing [SST]; Figure 2B). For example, six of ten miRNA quantified in follow-up experiments were selectively enriched in PV interneurons, despite the fact that these neurons share many properties with SST interneurons (Figure 2C; He et al.,

2012). Thus, while profiling at this single cell-type resolution has just begun, it is clear that crotamiton the miRNA landscape offers many opportunities to fine-tune the distinct developmental and functional properties of neuronal subpopulations. Even within a single neuron, complex functional architecture offers many compartments that could be regulated by different sets of miRNA. An early comparison between miRNA in the cell bodies and neurites of rodent hippocampal neurons showed a graded distribution across a set of 99 candidates, the extremes of which defined miRNA that are selectively enriched in dendrites versus soma (Kye et al., 2007). This study also examined miRNA copy number and estimated an average of 10,000 copies per cell, a number that is within an order of magnitude of average synapse number per neuron, thus raising the intriguing question of whether synaptic miRNA can be locally effective in very small numbers. Nonetheless, the synaptic compartment appears to contain a large fraction of the neuronal miRNA pool. Recent analysis of miRNA representation in synaptoneurosome fractions from five different rodent brain regions showed that roughly half of the miRNA genes tested were enriched in this synaptic material (Pichardo-Casas et al.