Classey, John David; (1998) Postnatal development of the primate prefrontal cortex (areas 9 and 46): maturation of pyramidal neurons and serotonergic innervation in layer 3. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The dorsolateral prefrontal cortex (DLPFC) of the monkey brain exhibits a unique combination of intraareal and interareal connections, as well as distinctive neuronal properties, which correlate with diverse cognitive and mnemonic behaviours. Many of these attributes are found in the homologous region of the human brain. This thesis describes and compares the developmental time courses of two important components of the cortical circuitry in the monkey DLPFC: pyramidal neurons providing extensive, elaborately-patterned intrinsic connections in the superficial layers and the serotonin (5-HT) innervation in the same region. We hope that the results from these studies will contribute to a model of the human DLPFC; aiding the understanding of complex interactions within the DLPFC during postnatal development. The layer 3 pyramidal neurons providing intrinsic lattice connectivity within layers 1-3, are also the sources and targets for efferent and afferent corticocortical connections between the DLPFC and the rest of the brain. The postnatal time course of maturation for layer 3 pyramidal neurons was quantified by means of the changes in the relative density of their dendritic spines, which represent the postsynaptic sites of excitatory (asymmetric) synapses. We compared the developmental sequence for dendritic spines to the time courses of maturation for other components of layer 3 circuitry, e.g. asymmetric synapses, inhibitory parvalbumin-immunoreactive (PV-IR) cartridges, dopaminergic (DAergic) axons and we comment on possible implications for observed temporal similarities or differences between them. Layer 3 is also the site of a dense 5-HTergic axon innervation, which originates from the mid-brain raphe nuclei and comprises 2 classes of axon fibres ("thick" and "thin"). We examined the time-scale of postnatal development for 5-HTergic axons in layer 3 and attempted to find temporal correlation's between 5-HT axon maturation and pyramidal neuron dendritic spine development, as well as with previously examined layer 3 components, including DAergic axons and 5-HT tissue concentration. Findings included the demonstration of concurrent time courses of maturation for dendritic spines and PV-IR cartridges; synchrony between rates of spine and excitatory synapse production in the first 2 postnatal months and a subsequent plateau phase, but different time periods of decline (from 1.5 and 3.0 years, respectively) and complex relationships between the stages of spine maturation and changes in density of DAergic axons coinciding with the rise (birth-2 months) and fall (1.5-4.6 years) of spine numbers. We also demonstrated temporal interrelations between 5-HTergic axon development and that of other neuropil components, including modulatory interaction between the density of 5-HTergic axons and dendritic spines as well as strong reciprocal correlation's between the 5-HTergic and DAergic axon innervations.

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