Excitatory and inhibitory neurotransmitters in the generation and degeneration of hippocampal neuroarchitecture

Mark P. Mattson, S. B. Kater

Research output: Contribution to journalArticle

Abstract

The possibility that excitatory and inhibitory inputs to neurons can affect the generation and degeneration of neuroarchitecture was examined in hippocampal pyramidal neurons in isolated cell culture. Dendritic outgrowth and cell survival were directly monitored in neurons exposed to: the excitatory neurotransmitter glutamate, the inhibitory transmitter GABA, anticonvulsants or combinations of these agents. Glutamate caused a graded series of changes in pyramidal neuron cytoarchitecture: a selective inhibition in dendritic outgrowth and dendritic pruning was observed with subtoxic levels of glutamate while cell death was induced by higher levels. Low levels of GABA alone or in combination with diazepam, carbamazepine, phenobarbital or phenytoin were without effect on dendrite outgrowth while higher levels caused moderate reductions in outgrowth. Neither GABA nor the anticonvulsants affected cell survival. GABA plus diazepam, phenobarbital, carbamazepine and phenytoin each significantly reduced the dendritic regression and cell death normally caused by glutamate. Elevation of extracellular K+ to 50 mM caused dendritic regression and 100 mM K+ caused cell death; these effects were greatly reduced by GABA and anticonvulsants. The calcium channel blocker Co2+ prevented the dendritic regression and cell death caused by both glutamate and K+ indicating that calcium influx was required for the neuroarchitectural responses. Taken together, these results demonstrate that neurotransmitters and neuromodulatory drugs can have direct and interactive effects on both neurite outgrowth and cell survival. Such neurotransmitter actions may play roles in both the formation and degeneration of the neuronal circuits in which they participate in information coding.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalBrain Research
Volume478
Issue number2
DOIs
StatePublished - Jan 30 1989
Externally publishedYes

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gamma-Aminobutyric Acid
Neurotransmitter Agents
Glutamic Acid
Cell Death
Anticonvulsants
Dendritic Cells
Cell Survival
Pyramidal Cells
Carbamazepine
Phenytoin
Phenobarbital
Diazepam
Neurons
Neuronal Plasticity
Calcium Channel Blockers
Dendrites
Cell Culture Techniques
Calcium
Pharmaceutical Preparations

Keywords

  • Calcium
  • Dendritic outgrowth
  • Diazepam
  • Glutamate
  • Hippocampus
  • Neurodegeneration
  • Pyramidal neuron
  • γ-Aminobutyric acid

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Excitatory and inhibitory neurotransmitters in the generation and degeneration of hippocampal neuroarchitecture. / Mattson, Mark P.; Kater, S. B.

In: Brain Research, Vol. 478, No. 2, 30.01.1989, p. 337-348.

Research output: Contribution to journalArticle

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