Spinogenesis and synaptic pruning during development are widely believed to subserve connectional specificity in the mature CNS via Hebbian-type reinforcement. Refinement of neuronal circuit through this "use it or lose it" principle is considered critical for brain development. Here we demonstrate that the magnitude of spinogenesis and pruning in the basal dendritic trees of pyramidal cells differ dramatically among sensory, association, and executive cortex. Moreover, somewhat counterintuitively, we demonstrate that the dendritic trees of pyramidal cells in the primary visual area actually lose more spines than they grow following the onset of visual experience. The present findings reveal that the process of synaptic refinement differs not only according to time, but also location.

Neocortical pyramidal cells are characterized by markedly different structure among cortical areas in the mature brain. In the ventral visual pathway of adult primates, pyramidal cells become increasingly more branched and more spinous with anterior progression through the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. It is not known how these regional specializations in neuron structure develop. Here, we report that the basal dendritic trees of layer III pyramidal cells in V1, V2, V4, TEO, and TE were characterized by unique growth profiles. Different numbers of spines were grown in the dendritic trees of cells among these cortical areas and then subsequently pruned. In V1, V2, and V4, more spines were pruned than grew resulting in a net decrease in the number of spines in the dendritic trees following the onset of visual experience. In TEO and TE, neurons grew more spines than they pruned from visual onset to adulthood. These data suggest that visual experience may influence neuronal maturation in different ways in different cortical areas.

Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment. Early postnatally, synaptogenesis was reduced in this model, while juvenile-age VPA-treated marmosets showed increased synaptogenesis, similar to observations in human tissue. During infancy, synaptic plasticity transiently increased and was associated with altered vocalization. Synaptogenesis-related genes were downregulated early postnatally. At three months of age, the differentially expressed genes were associated with circuit remodeling, similar to the expression changes observed in humans. In summary, we provide a functional and molecular characterization of a non-human primate model of ASD, highlighting its similarity to features observed in human ASD.

Abnormalities in the processes of the generation and/or pruning of dendritic spines have been implicated in several mental disorders including autism and schizophrenia. We have chosen to examine the common marmoset (Callithrix jacchus) as a primate model to explore the processes. As a first step, we studied the postnatal development of basal dendritic trees and spines of layer-III pyramidal cells in the primary visual sensory cortex (V1), a visual association cortex (inferior temporal area, TE), and a prefrontal cortex (area 12, PFC). Basal dendrites in all three areas were longer in adulthood compared with those in the newborn. In particular, rapid dendritic growth occurred in both TE and PFC around the second postnatal month. This early growth spurt resulted in much larger dendritic arbors in TE and PFC than in V1. The density of the spines along the dendrites peaked at 3 months of age and declined afterwards in all three areas: the degree of spine pruning being greater in V1 than in TE and PFC. The estimates of the total numbers of spines in the basal dendrites of a single pyramidal cell were larger in TE and PFC than in V1 throughout development and peaked around 3 months after birth in all three areas. These developmental profiles of spines and dendrites will help in determining assay points for the screening of molecules involved in spinogenesis and pruning in the marmoset cortex.

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