Dendritic development of retinal ganglion cells after prenatal intracranial infusion of tetrodotoxin

Abstract

The dendritic form of a cell may be established by many factors both intrinsic and environmental. Blockade of action potentials along the course of axons and in their postsynaptic targets dramatically alters the development of axonal morphology. The extent to which blockade of target cell activity retrogradely alters the dendritic morphology of the presynaptic cells is unknown. To determine whether the establishment of dendritic form by developing retinal canclion cells depends on activity within their targets, the sodium channel blocker, tetrodotoxin (TTX), was administered via minipumps to the diencephalon of cat fetuses from embryonic day 43 (E43) to E57. At E57 retinae were removed and living retinal ganglion cells injected in vitro with Lucifer yellow to reveal their dendritic morphology. In the TTX-treated animals both alpha and beta types of retinal ganglion cells were present, as were putative gamma cells. Overall, the dendrites of retinal ganglion cells in TTX-treated animals appeared qualitatively and Quantitatively similar to those of untreated animals. The only significant change in the TTX-treated cases was a small increase in the number of dendritic spines on the non-beta cells. These results indicate that the acquisition of basic dendritic form of developing ganglion cells is not influenced by the action potential activity within their targets, and that it is also independent of the terminal branching patterns of their axons.

Mice Lacking Specific Nicotinic Acetylcholine Receptor Subunits Exhibit Dramatically Altered Spontaneous Activity Patterns and Reveal a Limited Role for Retinal Waves in Forming ON and OFF Circuits in the Inner Retina

“…Although a general blockade of action potentials with intraocular injections of tetrodotoxin had little effect on the dendritic structure of RGCs in both embryonic (Campbell et al, 1997) and postnatal cat retina (Wong et al, 1991), manipulations of neurotransmitter systems providing synaptic input to ganglion cells had more profound effects on RGC anatomy and function. For example, Sernagor and Grzywacz (1996) demonstrated that blockade of retinal wave activity in turtle retina with intraocular injection of the general nicotinic acetylcholine receptor (nAChR) antagonist D-tubocurarine prevented the dark-rearing-induced changes in RGC receptive fields.…”

Neurotrophic regulation of retinal ganglion cell synaptic connectivity: from axons and dendrites to synapses

“…When RGC axons were prevented from interacting with the tectum by transplanting the retina to ectopic locations or when the target specificity or size were altered, early RGC dendritic arbor development was morphologically unaffected, demonstrating that the target exerts relatively little control over the early phase of RGC dendritic differentiation (Campbell et al, 1997;Ramoa and Yamasaki, 1996;Sakaguchi, 1989;Vanselow et al, 1990). In support of early intrinsic mechanisms of RGC dendritogenesis is the observation that isolated RGCs, when placed in vitro, extend dendrites that cover territories similar to RGCs in intact retinas (Montague and Friedlander, 1991).…”

Activity-Dependent Cortical Target Selection by Thalamic Axons

“…n = 3) were studied from pregnant cats in our breeding colony of known gestational age. Anesthesia, sterile surgical techniques, and minipump implantations were according t o (22). After infusion of either 300 p M TTX or vehicle (300 p M sodium citrate buffer) between E42 and E56, the fetuses were delivered by cesarean section and were transcardially perfused (3).…”

“…9. Previous studies have demonstrated that intracranial minipump infusions of TTX produce concentrations that are sufficient t o block sodium-dependent action potentials bilaterally throughout the entire forebrain and midbrain at E42 t o E56 (22) and result in the failure of retinal ganglion axons t o segregate into eye-specific layers in the LCN (17,23). However, of MCN axons had already invaded the auditory cortical plate [A.…”