The Role of Neuritin—A Synapse-Maturating Protein—in Striatal Dendritic Morphology

Synapses are the sites where information processing occurs in the brain. They consist of a presynaptic terminal, which originates from the axon of the presynaptic cell, and a postsynaptic terminal, originating from the dendrite of the postsynaptic cell. Improper synapse formation and function results in numerous neurologic diseases, ranging from epilepsy to schizophrenia. Thus, by studying the molecular underpinnings of synapse formation, contributions to treatment and preventions of such diseases can be made. For instance, the striatum has been implicated in Parkinson’s, schizophrenia, and addiction. A major neuronal type in the striatum is a medium spiny neuron (MSN). To understand the mechanisms of synapse formation in the striatum, we looked into candidate molecules that might be involved in the dendritic development of MSNs. Our focus became neuritin (NRN), a glycosylphoshatidylinositol-anchored protein, since it has been shown to promote dendritic growth and synapse formation in other brain structures, such as the hippocampus and the cortex, and is highly expressed in the striatum. The effects of NRN were not examined, however, in the striatum; therefore, we studied the dendritic morphology of wild-type and NRN knockdown striatal MSNs by using the culture system. We quantified the results by determining the density of dendritic spines, small protrusions from the dendrite that directly receive input from the axon of the presynaptic cell. By separating the dendritic spines into two groups—mature and immature—we also quantified differences in spine maturation between the wild-type and knockdown neurons. We did not find significant differences in the spine densities or maturation of wild-type and neuritin knockdown MSNs. Thus, NRN does not have any apparent effect on MSNs within the 19 days in vitro that we studied, leading us to believe that NRN’s role in synapse formation might exist exclusively in brain structures capable of synaptic plasticity, the ability for synaptic change throughout life, since these types of structures have been linked to NRN thus far. It remains possible, however, that since striatal NRN expression persists into adulthood, NRN might become important for striatal synapse stabilization in adults—this point requires further investigation.