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Susana Cohen-Cory

Publications and source records attributed to Susana Cohen-Cory.

7 recordsLinked to original sources
PubMed2005

BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo.

Brain-derived neurotrophic factor (BDNF) modulates synaptic connectivity by increasing synapse number and by promoting activity-dependent axon arbor growth. Patterned neuronal activity is also thought to influence the morphological maturation of axonal arbors by directly influencing the stability of developing synapses. Here, we used in vivo time-lapse imaging to examine the relationship between synapse stabilization and axon branch stabilization, and to better understand the participation of BDNF in synaptogenesis. Green fluorescent protein (GFP)-tagged synaptobrevin II was used to visualize presynaptic specializations in individual DsRed2-labeled Xenopus retinal axons arborizing in the optic tectum. Neutralizing endogenous tectal BDNF with function-blocking antibodies significantly enhanced GFP-synaptobrevin cluster elimination, a response that was paralleled by enhanced branch elimination. Thus, synapse dismantling was associated with axon branch pruning when endogenous BDNF levels were reduced. To obtain a second measure of the role of BDNF during synapse stabilization, we injected recombinant BDNF in tadpoles with altered glutamate receptor transmission in the optic tectum. Tectal injection of the NMDA receptor antagonists APV or MK801 transiently induced GFP-synaptobrevin cluster dismantling, but did not significantly influence axon branch addition or elimination. BDNF treatment rescued synapses affected by NMDA receptor blockade: BDNF maintained GFP-synaptobrevin cluster density by maintaining their addition rate and rapidly inducing their stabilization. Consequently, BDNF influences synaptic connectivity in multiple ways, promoting not only the morphological maturation of axonal arbors, but also their stabilization, by a mechanism that influences both synapses and axon branches.

Animals↗
PubMed2004

Embryonic GABAergic spinal commissural neurons project rostrally to mesencephalic targets.

Although spinal commissural neurons serve as a model system for studying the mechanisms that underlie axonal pathfinding during development, little is known about their synaptic targets. Previously we identified a group of ventromedially located commissural neurons in rat spinal cord that are gamma-aminobutyric acid (GABA)-ergic and express L1 CAM on their axons. In this study, serial sagittal sections of embryos (E12-15) were processed for glutamic acid decarboxylase (GAD)-65 and L1 immunocytochemistry and showed labeled commissural axons coursing rostrally within the ventral marginal zone. Both GAD65- and L1-positive axons extended rostrally out of the spinal cord into the central part of the medulla and then into the midbrain. GAD65-positive axons branched and ended abruptly within the lateral midbrain. To determine the targets of these ventral commissural neurons, embryos (E13-15) were injected with DiI into the ventromedial spinal cord. At all three ages, DiI-labeled axons projected rostrally in the contralateral ventral marginal zone, turned into the central medulla, and then traveled to the midbrain. DiI-labeled axons appeared to terminate in the lateral midbrain by branching into small, punctate structures. In reciprocal experiments, DiI injected into the lateral midbrain identified an axon pathway that coursed through the brainstem, into the spinal cord ventral marginal zone, and then filled cell bodies in the contralateral ventromedial spinal cord. A spatial and temporal coincidence was apparent between the GAD65/L1- and the DiI-labeled pathways. Together these findings suggest that some GABAergic commissural neurons are early projection neurons to midbrain targets and most likely represent a spinomesencephalic pathway to the midbrain reticular formation.

Afferent Pathways↗
PubMed2004

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

This review highlights important events during the morphological development of retinal ganglion cells (RGCs), focusing on mechanisms that control axon and dendritic arborization as a means to understand synaptic connectivity with special emphasis on the role of neurotrophins during structural and functional development of RGCs. Neurotrophins and their receptors participate in the development of visual connectivity at multiple levels. In the visual system, neurotrophins have been shown to exert various developmental influences, from guiding the morphological differentiation of neurons to controlling the functional plasticity of visual circuits. This review article examines the role of neurotrophins, and in particular of BDNF, during the morphological development of RGCs, and discusses potential interactions between activity and neurotrophins during development of neuronal connectivity.

Animals↗
PubMed2003

Basal forebrain cholinergic system is involved in rapid nerve growth factor (NGF)-induced plasticity in the barrel cortex of adult rats.

We have previously reported that topical application of nerve growth factor (NGF) to the barrel cortex of an adult rat rapidly augmented a whisker functional representation (WFR) by increasing its area and height within minutes after NGF application. In addition, we found that TrkA, the high-affinity NGF receptor, was only found on fibers projecting into the barrel cortex. Here we use a combination of techniques including chronic intrinsic signal optical imaging, neuronal fiber tracking and immunohistological techniques, to test the hypothesis that NGF-induced rapid cortical plasticity is mediated by the cortical projections of the basal forebrain cholinergic system (BFCS). Our studies localize the source of the cells in the BFCS that project to a single WFR and also demonstrate that TrkA-immunoreactive fibers in the cortex are also cholinergic and likely arise from the BFCS. In addition, by selectively lesioning the BFCS cortical fibers with the immunotoxin 192 IgG-saporin, we show that NGF-induced WFR-cortical plasticity is eliminated. These results, taken together with our previously reported imaging results that demonstrated that agonists of the cholinergic system (particularly nicotine) showed transient NGF-like augmentations of a WFR, implicate the BFCS cortical projections as necessary for NGF's rapid plasticity in the adult rat somatosensory cortex.

Acetylcholine↗
PubMed2002

The developing synapse: construction and modulation of synaptic structures and circuits.

Synapse formation and stabilization in the vertebrate central nervous system is a dynamic process, requiring bi-directional communication between pre- and postsynaptic partners. Numerous mechanisms coordinate where and when synapses are made in the developing brain. This review discusses cellular and activity-dependent mechanisms that control the development of synaptic connectivity.

Animals↗
PubMed2002

Local and target-derived brain-derived neurotrophic factor exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo.

The dendritic and axonal arbors of developing retinal ganglion cells (RGCs) are exposed to two sources of BDNF: RGC dendrites are exposed to BDNF locally within the retina, and RGC axons are exposed to BDNF at the target, the optic tectum. Our previous studies demonstrated that increasing tectal BDNF levels promotes RGC axon terminal arborization, whereas increasing retinal BDNF levels inhibits RGC dendritic arborization. These results suggested that differential neurotrophic action at the axon versus dendrite might be responsible for the opposing effects of BDNF on RGC axonal versus dendritic arborization. To explore this possibility, we examined the effects of altering BDNF levels at the optic tectum on the elaboration of RGC dendritic arbors in the retina. Increasing tectal BDNF levels resulted in a significant increase in dendritic branching, whereas neutralizing endogenous tectal BDNF with function-blocking antibodies significantly decreased dendritic arbor complexity. Thus, RGC dendritic arbors react in opposing manners to retinal- versus tectal-derived BDNF. Alterations in retinal BDNF levels, however, did not affect axon terminal arborization. Thus, RGC dendritic arborization is controlled in a complementary manner by both local and target-derived sources of BDNF, whereas axon arborization is modulated solely by neurotrophic interactions at the target. Together, our results indicate that developing RGCs modulate dendritic arborization by integrating signals from discrete sources of BDNF in the eye and brain. Differential integration of spatially discrete neurotrophin signals within a single neuron may therefore finely tune afferent and efferent neuronal connectivity.

Animals↗