Growth of pyramidal, but not non‐pyramidal, dendrites in long‐term organotypic explants of neonatal rat neocortex chronically exposed to neurotrophin‐3

Abstract

The present study was undertaken to determine the effects of neurotrophin-3 (NT3) and spontaneous bioelectric activity (SBA) on dendritic elongation and branching in long-term isolated organotypic explants of rat neocortex. Viral vector-directed expression of NT3 was used as an effective means to ensure a continuous, local production of the neurotrophic factor. Quantitative light microscopic measurement of dendritic branching patterns was carried out on Golgi-stained materials. Explants were exposed to an adenoviral vector encoding the genetic sequence for neurotrophin-3 (Ad-NT3), or to exogenous additions of the neuropeptide NT3. In order to test for activity-dependent growth effects under control and experimental conditions, explants were exposed to glutamatergic blockade using a cocktail of APV and DNQX. Both Ad-NT3 and NT3 peptide potently promoted apical and basal dendritic growth (elongation and branching) in pyramidal neurons. This growth was observed to be significant in layers II-IV and V. These growth effects were also not activity dependent, inasmuch as they were elicited from explants in which spontaneous bioelectric activity had been suppressed. Non-pyramidal neurons, throughout the neocortical slice, showed no significant dendritic responses to the prolonged presence of NT3. These findings show that pyramidal dendritic growth in long-term neocortical explants responds to at least one neurotrophic growth factor, NT3, and is independent of intrinsic bioelectric activity. The use of viral vectors in delivering a continuous high level of neurotrophic factor within developing neural tissues demonstrates its potential application to in vivo tissues during development, or in the stimulation of neuritogenesis and neuroregeneration following injuries.

Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5

“…NT3 increases dendritic complexity of hippocampal and cortical pyramidal cells independent of glutamate-mediated transmission (Morfini et al, 1994;Baker et al, 1998), and NT4/5 promotes the dendritic development (this study) and the neuropeptide Y expression in the absence of activity (Wirth et al, 1998). Although apical dendrites are fairly promiscuous, NT4/5 and NT3 are highly effective (e.g.…”

“…In pyramidal neurons, exogenous BDNF, NT4/5 (NTF5 -Mouse Genome Informatics) and NT3 (NTF3 -Mouse Genome Informatics), as well as neutralization of endogenous neurotrophins exert layer-specific effects on dendritic growth and branching, with BDNF affecting only active neurons (McAllister, 2000;Baker et al, 1998;Niblock et al, 2000). BDNF also increases dendritic length of hippocampal interneurons (Marty et al, 1996).…”

NGF Controls Dendrite Development in Hippocampal Neurons by Binding to p75NTRand Modulating the Cellular Targets of Notch

“…A contribution of neurotrophins to the regulation of dendrite morphology has already been demonstrated in a variety of preparations (McAllister et al, 1995(McAllister et al, , 1997Baker et al, 1998;Jin et al, 2003). As neurotrophins are released in an activity-dependent manner, they can play a major role in the structural adjustment of developing and mature neuronal circuits (reviewed in Whitford et al, 2002).…”

Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons

“…Many growth factors have been found to stimulate dendritic growth (Higgins et al, 1997), but two families appear to have especially prominent and widespread effects. Members of the BMP (bone morphogenetic protein) family enhance dendritic growth in sympathetic, spinal motor, cortical, striatal, and hippocampal neurons (Lein et al, 1995;Withers et al, 2000;Esquenazi et al, 2002;Gratacos et al, 2002), whereas various neurotrophins increase the growth of these processes in cortex (McAllister et al, 1995;Baker et al, 1998), retina (Lom et al, 2002), and cerebellum (Schwartz et al, 1997). Moreover, there is evidence for interactions between these two classes of stimulatory molecules, with sympathetic neurons requiring simultaneous exposure to both a member of the BMP family and to nerve growth factor (NGF) for optimal dendritic growth (Lein et al, 1995).…”