The ontogeny and functional distribution of novel, neurochemically-defined columns in mammalian visual cortex

The synaptic organization of the mammalian visual cortex is susceptible to activity- and experience-dependent modifications during a distinct temporal window of development. In an effort to understand the synaptic mechanisms responsible for initiating and maintaining this period of plasticity, the studies presented in this thesis describe the ontogenic distribution of specific molecular indices of serotonergic and glutamatergic neurotransmission in the developing kitten visual cortex and evaluate their patterns of expression following manipulations of early visual experience. The distributions of serotonin (5-HT) 1A, 1C, 2 and 3 receptor subtypes and the 5-HT uptake site were assessed in postnatal cat visual cortex using in vitro autoradiographic methods. Each5-HT receptor subtype exhibited a unique temporal, regional and laminar pattern of expression. The density of 5-HTiA receptors was highest within superficial and deep cortical layers around postnatal day (PD) 30, while 5-HTic and 5-HT2 receptors exhibited peak levels in middle cortical layers at PD50 and PD120, respectively. Between PD30 and PD90, 5-HTic & 5-HT2 receptors were expressed at high levels within the same columnar compartments, but within different geniculate-recipient layers of area 17. These columns of 5-HT receptors measured about 400 [t,m wide with a centre-to-centre spacing of approximately 900 Inn. The ontogenic distribution of synaptic zinc (Zn), a vesicular component of a subset of glutamatergic-neuron terminals, was also examined in the cat visual cortex. In the adult, intense Zn-staining was highest in superficial and deep layers. The relative absence of Zn in layer IV conspicuously distinguished visual cortical areas 17 and 18 from adjacent cortical regions. The earliest Zn-positive staining in visual cortex was apparent by PD2 and was restricted to a thin layer at the bottom of the cortical plate. By PD 10, and continuing through PD20, synaptic zinc formed a trilaminar pattern of dense staining in areas 17 and 18, which included the top of layer I, and layers III and V. The laminar pattern of synaptic zinc in visual cortex appeared mature by PD30, except that the distribution of zinc in layer IV was not uniform. When examined in the tangential plane at PD50, Zn-rich patches were found to demarcate columnar compartments in layer IV of area 17.The columnar expression of Zn exhibited similar temporal and spatial characteristics as 5-HT1c/2receptor columns. When compared in adjacent sections at PD50, columns demarcated by 5-HTic/2receptors and Zn were found to be precisely coaligned. The input- and activity-dependence of the organization of Zn / 5-HT receptor columns was addressed by constraining cortical visual experience. Lesions produced in early development, which interfered with normal binocular input to visual cortex, had similar detrimental effects on the columnar distributions of 5-HT 1 ci 2 receptors and Zn, and indicated that the columnar compartmentalization of these molecules was dependent on normal visual input and activity. Zn /5-HT receptor-rich columns were found to be precisely complementary to columns rich incytochrome oxidase (CO) and acetylcholinesterase (AChE), molecules which are known to describe functional columnar compartments in primate visual cortex. Zn and CO were also found to describe an interdigitated columnar mosaic in primate visual cortex, suggesting that these molecules might demarcate functionally homologous columnar compartments in the visual cortex of these phylogenetically distinct species. The results of these experiments suggest that serotonergic and zinc-containing glutamatergic processes may play important roles in the postnatal development of mammalian visual cortex, particularly with regard to mechanisms of compartmentalization into functional columnar domainsMedicine, Faculty ofGraduat