Biomedical subjects

Vandana Mehta

Publications and source records attributed to Vandana Mehta.

3 recordsLinked to original sources

PubMed2006

Early neural activity and dendritic growth in turtle retinal ganglion cells.

Early neural activity, both prenatal spontaneous bursts and early visual experience, is believed to be important for dendritic proliferation and for the maturation of neural circuitry in the developing retina. In this study, we have investigated the possible role of early neural activity in shaping developing turtle retinal ganglion cell (RGC) dendritic arbors. RGCs were back-labelled from the optic nerve with horseradish peroxidase (HRP). Changes in dendritic growth patterns were examined across development and following chronic blockade or modification of spontaneous activity and/or visual experience. Dendrites reach peak proliferation at embryonic stage 25 (S25, one week before hatching), followed by pruning in large field RGCs around the time of hatching. When spontaneous activity is chronically blocked in vivo from early embryonic stages (S22) with curare, a cholinergic nicotinic antagonist, RGC dendritic growth is inhibited. On the other hand, enhancement of spontaneous activity by dark-rearing (Sernagor & Grzywacz (1996)Curr. Biol., 6, 1503-1508) promotes dendritic proliferation in large-field RGCs, an effect that is counteracted by exposure to curare from hatching. We also recorded spontaneous activity from individual RGCs labelled with lucifer yellow (LY). We found a tendency of RGCs with large dendritic fields to be spontaneously more active than small-field cells. From all these observations, we conclude that immature spontaneous activity promotes dendritic growth in developing RGCs.

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PubMed2006

Receptive field structure-function correlates in developing turtle retinal ganglion cells.

Mature retinal ganglion cells (RGCs) have distinct morphologies that often reflect specialized functional properties such as On and Off responses. But the structural correlates of many complex receptive field (RF) properties (e.g. responses to motion) remain to be deciphered. In this study, we have investigated whether motion anisotropies (non-homogeneities) characteristic of embryonic turtle RGCs arise from immature dendritic arborization in these cells. To test this hypothesis, we have looked at structure-function correlates of developing turtle RGCs from Stage 23 (S23) when light responses emerge, until 15 weeks post-hatching (PH). Using whole cell patch clamp recordings, RGCs were labelled with Lucifer Yellow (LY) while recording their responses to moving edges of light. Comparison of RF and dendritic arbor layouts revealed a weak correlation. To obtain a larger structural sample of developing RGCs, we have looked at dendritic morphology in RGCs retrogradely filled with the tracer horseradish peroxidase (HRP) from S22 (when RGCs become spontaneously active, shortly before they become sensitive to light) until two weeks PH. We found that there was intense dendritic growth from S22 onwards, reaching peak proliferation at S25 (a week before hatching), while RGCs are still exhibiting significant motion anisotropies. Based on these observations, we suggest that immature anisotropic RGC RFs must originate from sparse synaptic inputs onto RGCs rather than from the immaturity of their growing dendritic trees.

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PubMed2005

GABA type-A activity controls its own developmental polarity switch in the maturing retina.

In the developing CNS, GABA(A) responses switch from early excitation to late mature inhibition. The developmental factors that induce the polarity switch remain to be unraveled. Here, we bring the first experimental evidence in vivo in the retina that chronic activation of GABA(A) receptors is necessary for the switch to occur and for the chloride extrusion mechanism (through the K+/Cl- cotransporter KCC2) to develop. Using a turtle model and calcium imaging, we investigated how chronic blockade of GABA(A) receptors with bicuculline during the period of the GABAergic polarity switch (from 1 week before hatching until 4 weeks after hatching) influences developmental changes in the patterns of spontaneously generated electrical activity in the retinal ganglion cell (RGC) layer. During that period, spontaneous activity normally switches from propagating waves to stationary patches of coactive cells, until correlated activity completely disappears. These changes in activity patterns coincide with the switch of GABA(A) responses from excitation to inhibition. When GABA(A) receptors are chronically blocked, GABA(A) responses remain excitatory and spontaneous waves keep propagating across the RGC layer. Concomitantly, the developmental upregulation of KCC2 is inhibited on dendritic processes in the inner plexiform layer, suggesting that the intracellular concentration of chloride remains higher, as in younger cells. This study presents the first demonstration in vivo that GABA autoregulates its developmental polarity switch, emphasizing the importance of GABAergic activity in controlling activity patterns in the maturing retina.

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