Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: An electorn microscopic study in the occipital cortex of postnatral rats

Brooks, William H.; Petit, Ted L.; LeBoutillier, Janelle C.; Lo, Robert C.

doi:10.1002/syn.890080107

Cited by 35 publications

(6 citation statements)

References 62 publications

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“…The reduction in the depth of the molecular layer and inhibition of developmental synaptogenesis that followed NMDA receptor antagonism is the opposite of the facilitatory effect on synaptogenesis that we previously observed with acute and/or chronic developmental administration of NMDA. Brief exposure to peripherally administered NMDA resulted in a rapid onset (within minutes) of synaptogenesis (Brooks et al, 1991), while chronic developmental administration of low doses of NMDA induced an increase in the depth of, and estimated total synapse number in, the occipital cortex molecular layer (Brooks et al, 1994). When considered along with the contrasting anatomical findings that followed increased NMDA receptor activity, the results of the current study suggest that the NMDA receptor plays an integral role in the process of developmental synaptogenesis and plasticity.…”

Section: Nmda Antagonist-induced Reductions In Synaptic Developmentmentioning

confidence: 53%

Effect of chronic administration of NMDA antagonists on synaptic development

Brooks

Petit

LeBoutillier

1997

Synapse

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The current research assessed the role of the N-methyl-D-aspartate (NMDA) receptor in developmental synaptic plasticity. This was accomplished by quantitative analysis of synaptic number and morphology following pharmacological manipulation of NMDA receptor activity using either the competitive antagonist 2-amino-5-phosphonovaleric acid (APV) or the noncompetitive antagonist phencyclidine (PCP). In the first group, 15-day-old male Long-Evans rats were implanted with osmotic minipumps, which administered 50 mM APV or vehicle at a rate of 0.5 microliter per h into the subjects' occipital cortex for 14 days. At age 30 days (P30), the rats were sacrificed and their occipital neocortices were examined. A second group of rats was given subcutaneous injections of 10 mg/kg PCP or vehicle once daily beginning on P5 for a period of 15 days, and was sacrificed on P20. To determine the effects following withdrawal from long-term NMDA antagonism, a third group of animals was given the same PCP injection routine until P20, but was sacrificed on P21, P26, P36, and P56. Developmental administration of APV was associated with a decreased molecular layer depth and estimated total number of synapses. Similarly, PCP induced a reduction in brain weight, molecular layer depth, and estimated total number of synapses. Withdrawal from NMDA antagonism was initially associated with similar results, i.e., reduced brain weight, cortex depth, synaptic density, and estimated total number of synapses, along with an increase in synaptic length. By P36, however, there was a transitory rebound associated with increased molecular layer depth and estimated total number of synapses. These results support the suggestion that NMDA receptor activation is integral to naturally occurring developmental synaptogenesis, and underscore the importance of NMDA receptor involvement in the process of synaptic plasticity.

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Section: Nmda Antagonist-induced Reductions In Synaptic Developmentmentioning

confidence: 53%

Effect of chronic administration of NMDA antagonists on synaptic development

Brooks

Petit

LeBoutillier

1997

Synapse

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“…Elsewhere in the brain, activation of NMDA-type glutamate receptors is thought to mediate events as diverse as the outgrowth of axonal processes (Rashid and Cambray-Deakin 1992), synapse formation (Brooks et al 1991) and cell death (Nichol et al 1995). In accord with such findings, Bodnarenko and Chalupa (1993) have shown that the perturbation of glutamatergic function leads to abnormal stratification of dendrites of defined populations of retinal ganglion cells in the inner plexiform layer.…”

Section: Discussionmentioning

confidence: 89%

Changing patterns of spatial buffering of glutamate in developing rat retinae are mediated by the Müller cell glutamate transporter GLAST

Pow

Barnett

1999

Cell and Tissue Research

103

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The patterns of expression of the glutamate transporter GLAST were compared with the patterns of uptake of exogenous D-aspartate, which is a substrate for all glutamate transporters. At postnatal day 0, fine radial processes and end feet of presumptive Müller cells were weakly immunoreactive for GLAST. At postnatal day 3, intense labelling was associated with astrocytes enveloping newly formed blood vessels on the vitread surface of the retina. Between postnatal days 7 and 10, there was a rapid increase in the intensity of labelling in the Müller cells but clear stratification of GLAST-immunoreactive processes in the inner plexiform layer was not observed until postnatal day 14. By comparison, D-aspartate uptake was initially associated with a wide variety of cellular elements including most neuroblasts, presumptive Müller cells, and astrocytes associated with blood vessels but was absent from the somata of many neurons in the ganglion cell layer and amacrine cell layer. There was a gradual contraction in the numbers of cells that were able to take up D-aspartate, such that, by adulthood, uptake was restricted mainly to Müller cells and astrocytes. We conclude that, during early retinal development, the low levels of GLAST expression by Müller cells permit D-aspartate, and by inference, glutamate, to permeate the retina freely, thus allowing uptake by other glutamate transporters on other cell types. As the retina matures, increased expression of GLAST by Müller cells restricts the access of D-aspartate to other cellular compartments in the retina. This changing pattern of spatial buffering of glutamate by GLAST probably has significant implications regarding our understanding of the role of glutamate during processes such as retinal synaptogenesis.

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“…Direct injections of NMDA into the occipital cortex of 8-day-old rats (age at which there is a peak vulnerability to both NMDA injections and HI [61]) resulted in an increase in synaptic density (number of synapses) [62]. Conversely, NMDA receptor blockade resulted in a decrease in the total number of synapses [63], and was associated with deficits in learning and memory [77], thus confirming an important role of the NMDA receptor in synaptogenesis.…”

Section: Under Normal Conditionsmentioning

confidence: 92%

“…Synaptic plasticity (synaptogenesis) is the key factor in shaping the wiring pattern of the brain, and is responsible for the mechanism of learning and memory [62,63,76]. Direct injections of NMDA into the occipital cortex of 8-day-old rats (age at which there is a peak vulnerability to both NMDA injections and HI [61]) resulted in an increase in synaptic density (number of synapses) [62].…”

Section: Under Normal Conditionsmentioning

confidence: 99%

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NMDA Receptors in the Developing Brain and Effects of Noxious Insults

Waters¹,

Machaalani²

2004

Neurosignals

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This review covers normal expression of the NMDA receptor in the fetus and newborn, and then the response of the NMDA receptors within the central nervous system (CNS) during early development, to noxious stimuli. In the research setting, hypoxia is a commonly studied noxious stimulus that has been studied in a variety of contexts, including isolated hypoxia, or hypoxia combined with ischemia or hypercapnia, and delivered in single or repeated doses (intermittent stimuli). We review differences and commonalities between these experimental paradigms, and the sequelae of a common outcome, which is cell death, possibly through excitotoxic mechanisms. Finally, based on current literature, we will examine potential directions for clinical therapeutic interventions. By highlighting knowledge gaps in this field, we hope to encourage future research focusing on clinically relevant problems and outcomes in this area.

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Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: An electorn microscopic study in the occipital cortex of postnatral rats

Cited by 35 publications

References 62 publications

Effect of chronic administration of NMDA antagonists on synaptic development

Effect of chronic administration of NMDA antagonists on synaptic development

Changing patterns of spatial buffering of glutamate in developing rat retinae are mediated by the Müller cell glutamate transporter GLAST

NMDA Receptors in the Developing Brain and Effects of Noxious Insults

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