Cytological Organization of the Dorsal Lateral Geniculate Nuclei in Mutant Anophthalmic and Postnatally Enucleated Mice
This report established the potential of mammalian central nervous system (CNS) neurons to survive and recruit connections in the total developmental absence of their major input. Previously, CNS plasticity was assessed using postnatally deafferented animals, a condition in which input fibers are present during the crucial stages of in utero development and are secondarily removed after birth. In the case of the mouse visual system, the retinal fibers reach the lateral geniculate nuclei approximately 7 days prior to birth. As a consequence, the previously published studies using postnatal deafferentation did not assess the role of input on the initial stages of neuronal differentiation and survival.
The results of our studies were: 1) the normal primary input fibers appear to have little role in the initial development and differentiation of phenotypically distinct types of visual system neurons; 2) synaptic sites normally restricted to visual inputs are capable of receiving alternative synaptic connections in the absence of the normal input; and 3) the total lack of normal input produces a greater likelihood of survival and remodeling of neurons than postnatal deafferentation. The implication is that initial differentiation of neuronal types is endogenously determined by specific gene expression, while the final shaping and synaptic arrangements are more plastic and possibly determined by an hierarchy of preferred associations with other cells. Interestingly, the more early the absence of primary input fibers the better the opportunity of neurons to recruit alternative inputs and survive.
This ability of the brain to adapt during early development was also reflected in a parallel study on congenitally blind mice in which we found that the cortical areas that normally receive visual input from the lateral geniculate nuclei are largely normal in terms of neuronal cell types, dendritic spine patterns, and synaptic associations. Therefore, the further "down the line" from the loss of primary input, the more likely the brain has maintained connections from afferent sources. It is unknown what information is being processed in the brain "vision" regions in the congenital absence of retinal input.