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I Rajan

Publications and source records attributed to I Rajan.

8 recordsLinked to original sources
PubMed2001

The scaffold protein, Homer1b/c, regulates axon pathfinding in the central nervous system in vivo.

Homer proteins are a family of multidomain cytosolic proteins that have been postulated to serve as scaffold proteins that affect responses to extracellular signals by regulating protein-protein interactions. We tested whether Homer proteins are involved in axon pathfinding in vivo, by expressing both wild-type and mutant isoforms of Homer in Xenopus optic tectal neurons. Time-lapse imaging demonstrated that interfering with the ability of endogenous Homer to form protein-protein interactions resulted in axon pathfinding errors at stereotypical choice points. These data demonstrate a function for scaffold proteins such as Homer in axon guidance. Homer may facilitate signal transduction from cell-surface receptors to intracellular proteins that govern the establishment of axon trajectories.

Animals↗
PubMed1999

Dendritic dynamics in vivo change during neuronal maturation.

In vivo imaging of optic tectal neurons in the intact Xenopus tadpole permits direct observation of the structural dynamics that occur during dendritic arbor formation. Based on images of single DiI-labeled neurons collected at daily intervals over a period of 6 d, we divided tectal cell development into three phases according to the total length of the dendritic arbor. During phase 1, the cell differentiates from a neuroepithelial cell type and extends an axon out of the tectum. The total dendritic branch length (TDBL) is <100 micrometers. During phase 2, when TDBL is 100-400 micrometers, the dendritic arbor grows rapidly. During phase 3, when TDBL is >400 micrometers, the dendritic arbor grows slowly and appears stable. Neurons at different positions along the rostrocaudal developmental axis of the tectum were imaged at 2 hr intervals over 6 hr and at 24 hr intervals over several days. Images collected at 2 hr intervals were analyzed to determine rates of branch additions and retractions. Morphologically complex, phase 3 neurons show half the rate of branch additions and retractions as phase 2 neurons. Therefore, rapidly growing neurons have dynamic dendritic arbors, and slower-growing neurons are structurally stable. The change in growth rate and dendritic arbor dynamics from phase 2 to phase 3 correlates with the developmental increase in synaptic strength in neurons located along the rostrocaudal tectal axis. The data are consistent with the idea that strong synaptic inputs stabilize dendritic arbor structures and that weaker synaptic inputs are permissive for a greater degree of dynamic rearrangements and a faster growth rate in the dendritic arbor.

Animals↗
PubMed1999

NMDA receptor activity stabilizes presynaptic retinotectal axons and postsynaptic optic tectal cell dendrites in vivo.

To investigate the role of N-methyl-D-aspartate (NMDA) receptor activity in the stability of the presynaptic axon arbor and postsynaptic dendritic arbors in vivo, we took time-lapse confocal images of single DiI-labeled Xenopus retinotectal axons and optic tectal neurons in the presence and absence of the NMDA receptor antagonist, APV. Retinotectal axons or tectal neurons were imaged at 30-min intervals over 2 h, or twice over a 24-h period. Retinal axons in animals exposed to DL-APV (100 microM) showed an increase in rates of branch additions and a decrease in branch lifetimes over 2 h compared to untreated axons. Under the same experimental conditions, tectal neurons showed a decreased rate of branch tip additions and retractions. APV treatment over 24 h had no apparent effect on axon arbor morphology, but did decrease tectal cell dendritic arbor elaboration. These observations demonstrate that NMDA receptor activity in postsynaptic neurons stabilizes pre- and postsynaptic neuronal morphology in vivo.. However, when NMDA receptor activity is blocked, presynaptic retinal axons respond with increased arbor dynamics while postsynaptic tectal cell dendrites decrease arbor dynamics. Such differential responses of pre- and postsynaptic partners might increase the probability of coactive afferents converging onto a common target under conditions of lower NMDA receptor activity.

Animals↗
PubMed1998

Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo.

Glutamatergic retinotectal inputs mediated principally by NMDA receptors can be recorded from optic tectal neurons early during their morphological development in Xenopus tadpoles. As tectal cell dendrites elaborate, retinotectal synaptic responses acquire an AMPA receptor-mediated synaptic component, in addition to the NMDA component. Here, we tested whether glutamatergic activity was required for the elaboration of dendritic arbors in Xenopus optic tectal neurons. In vivo time-lapse imaging of single DiI-labeled neurons shows that the NMDA receptor antagonist APV (100 microM) blocked the early development of the tectal cell dendritic arbor, whereas the AMPA receptor antagonist CNQX (20 microM) or the sodium channel blocker TTX (1 microM) did not. The decreased dendritic development is attributable to failure to add new branches and extend preexisting branches. These observations indicate that NMDA-type glutamatergic activity promotes the initial development of the dendritic arbor. At later stages of tectal neuron development when AMPA receptor-mediated synaptic transmission is strong, both APV and CNQX decrease dendritic arbor branch length, consistent with a role for glutamatergic synaptic transmission in maintaining dendritic arbor structure. These results indicate that AMPA and NMDA receptors can differentially influence dendritic growth at different stages of neuronal development, in correlation with changes in the relative contribution of the receptor subtype to synaptic transmission.

2-Amino-5-phosphonovalerate↗
PubMed1998

Heart rate variability as an index of cue reactivity in alcoholics.

BACKGROUND: Autonomic responses follow exposure to conditioned stimuli such as contextual factors associated with alcohol ingestion. Heart rate variability is under autonomic control and may be a measure of such response. METHODS: Twenty alcoholics and 23 matched social drinkers (all male) were exposed to a neutral cue and then an alcohol cue in identical settings, during which the electrocardiogram of these subjects was recorded. Time and frequency domain parameters of heart rate variability (HRV) were computed by a blind rater. RESULTS: Coefficient of variation of R-R intervals and absolute powers of HRV spectrum (in frequency bands 0.05-0.15 Hz and 0.01-0.05 Hz) following alcohol cue were significantly higher in alcoholics than social drinkers. The mean heart rate (MHR) failed to reflect this difference. CONCLUSIONS: HRV paradigm appears more sensitive than MHR to measure cue reactivity.

Adult↗
PubMed1997

Mesodermal guidance of pioneer axon growth.

Pioneer axons in insect legs are experimentally accessible model systems for the molecular identification and cellular localization of guidance cues regulating the path of axon growth. A detailed study of the Fe2 pioneer axons in the legs of the cockroach was performed to examine the diversity of guidance mechanisms. A detailed microscopic analysis of the axons at various points in their trajectory indicates that the Fe2 axons grow on a mesodermal substratum which contains the cues guiding their growth along a stereotyped path. An identified pair of muscle pioneer cells (MPC) are likely to play an important role in enabling the Fe2 growth cones to respond to mesodermal guidance cues. The addition of heparan sulfate, heparitinase, and phosphatidylinositol-specific phospholipase C to the medium perturbs the in situ path of growth of the Fe2 axons and the location of the MPC in cultured embryos. This indicates a role for heparan sulfate proteoglycans and glycosylphosphatidylinositol-anchored proteins in axon guidance. When these results are compared to those of similar experiments performed on the well-characterized Ti1 axons, they indicate significant differences in the mechanisms that are used for axon guidance. The Fe2 neurons are a good model for elucidating the mechanisms used to guide axon growth on nonmuscle mesodermal substrates often encountered in the periphery of vertebrate embryos.

Animals↗
PubMedDate not supplied

RET(Men2B)-transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf-/- or gfr alpha-1(-/-) mice.

Multiple endocrine neoplasia type 2B (MEN2B) syndrome is caused by a missense mutation in the RET gene, which replaces Met918 by Thr in the intracellular kinase domain of the protein. This single amino acid substitution transforms the receptor into a constitutively active monomeric kinase (RET(Men2B)) and produces an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies, and mucosal ganglioneuromas. The ligand, GDNF, stimulates RET activity through a co-receptor, GFR alpha-1. In vitro studies have shown that the kinase and mitogenic properties of RET(Men2B) are enhanced by GDNF/GFR alpha-1 stimulation. A relevant clinical question is whether ablation of either GDNF or GFR alpha-1 could alter penetrance or severity of the MEN2B syndrome. We report that ganglioneuromatous tumors caused by a RET(Men2B) transgene in mice are not affected grossly or microscopically by the absence of gdnf or gfr alpha-1. Loss-of-function mutations in ret, gdnf, or gfr alpha-1 cause pan-intestinal aganglionosis in mice. We find that expression of the RET(Men2B) transgene in enteric neural progenitors, after they colonize the gut, does not prevent intestinal aganglionosis associated with gdnf or gfr alpha-1 deficiency.

Acetylcholinesterase↗