Survey Of Cell-type Specific Gene Expression Changes In The Primate Brain

The most prominent differences between humans and other non-human primates are the upright walking, the reduced body hair, the enlarged brainand the increased intelligence. The study of underlying mechanisms in the context of evolution focuses on gene expression differences between tissues of distinct species. In most cases the transciptome of intact tissues is analyzed leaving cell-type specific differences unnoticed.Thus, in this study Laser Capture Microdissection (LCM) was used to detect expression changes in neuronal and glial cells of the prefrontal and cerebellar cortex from a rhesus macaque. As a result, when comparing the expression data of microdissected to non-microdissected tissue, LCM provides a deeper understanding of tissue divergence.Furthermore, determining whether genes specific for neuronal or glial cells show a human specific expression, revealed that in the PFC four-times and in the CBC two-times more neuron-specific genes than glial-specific genes show a human specific expression. This implies that neuronal cells specific for the prefrontal cortex participated stronger in the evolution of human cognitive abilities than glial cells.These human-specific genes expressed preferentially in neuronal cells of the PFC are involved in key features of the brain, such as "synaptic transmission" and "long-term potentiation". Some of these genes have previously been shown to be important for normal brain development, learning and memory as well as behavior. Furthermore, intracellular responses to several cellular pathways seem to be different in the human lineage, such as glutamate-GABA-and calcium/calmodulin-signaling pathways. This strongly suggests that the change in expression of these genes might have participated in the human brain evolution, being now important for several key features that determine the uniqueness of the human brain, such as memory, behavior and other higher cognitive abilities.