Structural and functional composition of the developing retinogeniculate pathway in the mouse

Abstract

The advent of transgenic mice has made the developing retinogeniculate pathway a model system for targeting potential mechanisms that underlie the refinement of sensory connections. However, a detailed characterization of the form and function of this pathway is lacking. Here we use a variety of anatomical and electrophysiological techniques to delineate the structural and functional changes occurring in the lateral geniculate nucleus (LGN) of dorsal thalamus of the C57/BL6 mouse. During the first two postnatal weeks there is an age-related recession in the amount of terminal space occupied by retinal axons arising from the two eyes. During the first postnatal week, crossed and uncrossed axons show substantial overlap throughout most of the LGN. Between the first and second week retinal arbors show significant pruning, so that by the time of natural eye opening (P12-14) segregation is complete and retinal projections are organized into distinct eye-specific domains. During this time of rapid anatomical rearrangement, LGN cells could be readily distinguished using immunocytochemical markers that stain for NMDA receptors, GABA receptors, L-type Ca2+ channels, and the neurofilament protein SMI-32. Moreover, the membrane properties and synaptic responses of developing LGN cells are remarkably stable and resemble those of mature neurons. However, there are some notable developmental changes in synaptic connectivity. At early ages, LGN cells are binocularly responsive and receive input from as many as 11 different retinal ganglion cells. Optic tract stimulation also evokes plateau-like depolarizations that are mediated by the activation of L-type Ca2+ channels. As retinal inputs from the two eyes segregate into nonoverlapping territories, there is a loss of binocular responsiveness, a decrease in retinal convergence, and a reduction in the incidence of plateau potentials. These data serve as a working framework for the assessment of phenotypes of genetically altered strains as well as provide some insight as to the molecular mechanisms underlying the refinement of retinogeniculate connections.

Formation of eye-specific retinogeniculate projections occurs prior to the innervation of the dorsal lateral geniculate nucleus by cholinergic fibers

“…On the basis of dual-labeling patterns of different tracers injected into each eye, we find that this process commences at P5 and is largely completed by P8. These observations agree with previous studies (Rossi et al, 2001;Muir-Robinson et al, 2002;Jaubert-Miazza et al, 2005). During this period, we found a small number of cholinergic fibers in the dlgn at P5, with the first clusters of such labeled fibers evident by P12 (Fig.…”

Visual thalamocortical circuits in parvalbumin-deficient mice

“…Although clear morphological differences were reported among relay cells, TC cells are not PV-ir and an analysis of their electrophysiological properties did not reveal any additional distinguishing characteristics (Krahe et al, 2011). The remaining neurons of mouse dLGN are PV-ir GABAergic interneurons, whose density may be as low as 10-20% (Arcelli et al, 1997;Jaubert-Miazza et al, 2005) as recently confirmed by the analysis of the ultrastructure of synaptic profiles (Bickford et al, 2010). Excitatory projections from dLGN to the visual cortex send collaterals to the visual sector of the reticular thalamic nucleus (RTN) (Rafols and Valverde, 1973;Baldauf, 2010).…”

Neuroinflammation: Ways in Which the Immune System Affects the Brain

“…Synaptic inputs from the ipsilateral and contralateral eyes compete for territory [30][31][32][33]. To achieve mature projection patterns, synaptic remodeling occurs, including synapse elimination as well as stabilization and elaboration of remaining synapses [34,35].…”