Neurophysiologic effects of folate compounds in hippocampus, in vitro

David B. Clifford, James A. Ferrendelli

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7 Scopus citations


Pteroylglutamic acid (PGA, folic acid) and related compounds were studied for their electropysiologic effects on guinea pig hippocampal slices in vitro. Folates are found to have marked neuroexcitatory actions in CA3 and lesser but substantial excitatory effects in CA1. The dentate gyrus is minimally activated by folates. Extracellular recordings in CA3 reveal augmentation in single unit activity, evoked responses, and at 50-100 μM PGA concentrations, spontaneous epileptiform discharges are generated. Progressive increase in PGA concentrations to at least 2 mM do not result in loss of this activity. At concentrations of 200 μM, epileptiform bursts in CA3, precede those in CA1 which are lost by sectioning the Schaeffer collateral pathway. However, with 500 μM PGA, spontaneous bursts occur in CA1 isolated from CA3. The change induced by PGA primarily affects the population spike resulting in lower stimulus threshold and higher amplitude response. Measurement of threshold concentration necessary to produce spontaneous epileptiform activity of folate related compounds reveals the following order of potency: pteroylglutamic acid (PGA) ≥ formyl tetrahydrofolic acid (folinic acid) > > methyltetrahydrofolate (MTHF) ≥ methotrexate (MTX) ≥ glutamic acid. Pteroic acid, pterin, N(p-aminobenzoyl) L-glutamic acid are inactive. Methotrexate does not diminish the response to PGA. Thus, the entire folate molecule is needed for full activity. Folates represent naturally occurring, highly epileptogenic compounds whose mechanism of action is not dependent on metabolic products. Possibly they act at a central receptor as a neuromodulator.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalBrain Research
Issue number2
StatePublished - May 5 1983


  • epilepsy
  • folate compounds
  • folic acid
  • hippocampal slices
  • kainic acid


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