User:StarsTeam1/Spinogenesis

Models of Spinogenesis


The formation and development of dendritic spines, or spinogenesis, is a current area of research and debate in neurobiology. Much of what is known about this process comes from imaging studies in Purkinje cells and pyramidal cells of rodents during the postnatal period of neuronal development. The exact relationship between spinogenesis and synaptogenesis is yet to be discovered. There are three main models of spinogenesis: the Soleto model, the Miller/Peters model, and the filopodial model. The current body of data suggests that the details of the spinogenesis process may vary depending on the cell type and area where it occurs.

Sotelo Model
The Sotelo model hypothesizes that dendritic spines grow independently from presynaptic axonal input. Results observed in Purkinje synaptogenesis formed the basis for this model. In the cerebellum, Purkinje cells receive input from the parallel fibers of granule cells.

Data collected from two mutant strains of mice: weaver, which lacked granule cells and the reeler, which exhibited a perturbation in granule cell migration, demonstrated dendritic spines could in fact contain postsynaptic densities without any input from functioning granule cells. Therefore, the presynaptic terminal has a minor role in spinogenesis. Data from other experiments further suggested ordering of the axonal terminals around the initial independent growth of the dendrite is important for maximizing the interaction between the pre and postsynaptic cells. Even though dendrite spines grow independently from pre-synaptic input, the resulting dendritic spines form new synaptic connections with the input, which leads to synaptogenesis.

Miller/Peters Model
In many species, spine formation in pyramidal neurons occurs after birth. For example, in rat neocortical pyramidal neurons, spinogenesis beings in the middle of postnatal week 1 and spine density increases continually during the first four weeks of life. Subsequently, spine density decreases with age. This finding is indicative of an initial overproduction with later elimination of synapses. Specifically, Miller proposes a three-stage model for spinogenesis in pyramidal neurons: In stage one, synapses made on immature spines are short, barely-protruding “stubbies.” In stage two, the presynaptic region of the axon swells and begins to protrude as synaptic vesicles accumulate. In stage three, the spine is fully formed as thin or mushroom shaped, with a defined neck and a bulbous body. Overall, this model suggests dendritic spines are induced by axonal terminals on dendrities by a successive outgrowth through a firmly attached spine to an elongated one.

Filopodial Model
The dendritic morphology of branched arbors seen in most mature neurons is initially smooth and uniform. Appendages called dendritic filopodia start to appear in almost all developing neurons and can be distinguished from spines due to their thin structure without a bulbous head and their dynamic instability. According to the filopodial model, dendritic filopodia differentiate into spines upon interacting with a terminal axon. Dendritic filopodia was initially suggested as a precursor to dendritic spines due to their existence during development and morphological similarity to spines. In Purkinje cells, dendritic filopodia at the tips of the dendrite, called terminal filopodia, are known to interact with the environment and function in dendritic growth. In his review, Vaughn proposed a “synaptotrophic” hypothesis where terminal filopodia pulls terminal axons towards the dendrite to initiate synaptic contact. Once synaptic interaction is initiated with contact, dendritic filopodia retracts and incorporate synapses by passing down the synaptic function to dendritic shaft, similar to the Miller/Peters model. Further synaptic interactions then stimulate formation of a mature dendritic spine at these synaptic locations.