Changes in connectivity that go beyond simple refinement of existing connections require axon branching and outgrowth, processes that can be modulated by activity [4].
Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development.
Our study shows that removal of oligodendrocytes strongly affects axonal targeting and refinement of nerve connections and that these effects are observed even before myelination is completed.
Taken together these results reinforce the hypothesis that vinpocetine treatment in alcohol exposed animals may improve the refinement of horizontal connections since optical imaging is limited to signal acquisition from superficial cortical layers.
Activity-dependent persistent synaptic modifications are generally thought to be the cellular mechanisms underlying the refinement of neuronal connections in the developing nervous systems [10], [11] and contributing to the processes of learning and memory in the mature brain [12], [13].
This review focuses on the latter developmental process, the emergence of neuronal circuits through the formation and refinement of synaptic connections.
As substantial rearrangement and refinement of synaptic connections occur in the first weeks in the dorsal horn (Fitzgerald, 2005), it is possible that dorsal horn microglia are enabling the refinement and rearrangement of synaptic connections and pruning of axonal projections, temporarily increasing the production of damage associated molecular patterns (DAMP).
Mice deficient in C1q or C3 exhibited large sustained defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons.
Although undoubtedly activity plays a critical part in the maintenance and refinement of synaptic connections, often via competitive mechanisms, evidence is building that it also drives the process of synapse formation itself.
As a consequence, synaptic transmission and plasticity are affected in young adulthood, when refinement of synaptic connections requires higher activity potentially leading to a loss of synaptic plasticity (Fatemi and Folsom, 2009).
