Morphometric examination of human and monkey retinal ganglion cells within the papillomacular area.

PURPOSE: To examine the morphology of the retinal ganglion cells (RGCs) in the lesser characterized area lying between the optic disk and the macula that consists of the central papillomacular area (PMA) and the arcuate papillomacular bundle (PMB). METHODS: Nineteen human and 10 monkey (Macaca fascicularis) retinas obtained after death were used in the study. Perikaryal, axonal, and dendritic silhouettes were examined by postvital application of the fluorescent dye DiI, which specifically labeled RGCs when placed onto the optic fiber layer. The retinas were freed from surrounding tissue, prepared as flat mounts on a nitrocellulose filter, and fixed overnight in 4% paraformaldehyde. DiI diffuses along the membranes of ganglion cell axons, thereby completely labeling them, their cell bodies, and dendrites, which enables the RGCs to be examined with fluorescence microscopy. RESULTS: In both species, midget cells represented most of the RGCs within the PMA (96.15%) and possessed small, umbrella-like dendrites oriented toward the deeper retinal layers. Parasol cells were less abundant in both species and had small, typical symmetric dendrites. Also along the PMB, midget cells represented most cells (91.52%), whereas only 8.47% could be categorized as parasol cells. In both species, parasol cells of the PMB extended dendrites, which were oriented perpendicular to the axons. CONCLUSIONS: The data show that the PMA and PMB mainly contain small midget cells of typical morphology and size but with atypically oriented dendrites, which are only characteristic for this retinal area.

Neuronal activation of Ras regulates synaptic connectivity.

A synRas mouse model was used expressing constitutively activated Ha-Ras (Val12 mutation) in neurons to investigate the role of Ras-MAPkinase signalling for neuronal connectivity in adult brain. Expression of the transgene in the cortex of these mice starts after neuronal differentiation is completed and allows to directly investigate the effects of enhanced Ras activity in differentiated neurons. Activation of Ha-Ras induced an increase in soma size which was sensitive to MEK inhibitor in postnatal organotypic cultures. Adult cortical pyramidal neurons showed complex structural rearrangements associated with an increased size and ramification of dendritic arborization. Dendritic spine density was elevated and correlated with a twofold increase in number of synapses. In acute brain slices of the somatosensory and of the visual cortex, extracellular field potentials were recorded from layer II/III neurons. The input-output relation of synaptically evoked field potentials revealed a significantly higher basal excitability of the transgenic mice cortex compared to wild-type animals. In whole cell patch clamp preparations, the frequency of AMPA receptor-mediated spontaneous excitatory postsynaptic currents was increased while the ratio between NMDA and AMPA-receptor mediated signal amplitude was unchanged. A pronounced depression of paired pulse facilitation indicated that Ras contributes to changes at the presynaptic site. Furthermore, synRas mice showed an increased synaptic long-term potentiation, which was sensitive to blockers of NMDA-receptors and of MEK. We conclude that neuronal Ras is a common switch of plasticity in adult mammalian brain sculpturing neuronal architecture and synaptic connectivity in concert with tuning synaptic efficacy.