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Increased basal synaptic inhibition of hippocampal area CA1 pyramidal neurons by an antiepileptic drug that enhances I(H).
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2010 Jan; Vol. 35 (2), pp. 464-72. - Publication Year :
- 2010
-
Abstract
- The hyperpolarization-activated cation current (I(H)) regulates the electrical activity of many excitable cells, but its precise function varies across cell types. The antiepileptic drug lamotrigine (LTG) was recently shown to enhance I(H) in hippocampal CA1 pyramidal neurons, showing a potential anticonvulsant mechanism, as I(H) can dampen dendrito-somatic propagation of excitatory postsynaptic potentials in these cells. However, I(H) is also expressed in many hippocampal interneurons that provide synaptic inhibition to CA1 pyramidal neurons, and thus, I(H) modulation may indirectly regulate the inhibitory control of principal cells by direct modulation of interneuron activity. Whether I(H) in hippocampal interneurons is sensitive to modulation by LTG, and the manner by which this may affect the synaptic inhibition of pyramidal cells has not been investigated. In this study, we examined the effects of LTG on I(H) and spontaneous firing of area CA1 stratum oriens interneurons, as well as on spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons in immature rat brain slices. LTG (100 microM) significantly increased I(H) in the majority of interneurons, and depolarized interneurons from rest, promoting spontaneous firing. LTG also caused an increase in the frequency of spontaneous (but not miniature) IPSCs in pyramidal neurons without significantly altering amplitudes or rise and decay times. These data indicate that I(H) in CA1 interneurons can be increased by LTG, similarly to I(H) in pyramidal neurons, that I(H) enhancement increases interneuron excitability, and that these effects are associated with increased basal synaptic inhibition of CA1 pyramidal neurons.
- Subjects :
- 4-Aminopyridine pharmacology
Action Potentials drug effects
Animals
Animals, Newborn
Biophysics methods
Cadmium Chloride pharmacology
Calcium Channel Blockers pharmacology
Electric Stimulation methods
Excitatory Amino Acid Antagonists pharmacology
In Vitro Techniques
Interneurons drug effects
Lamotrigine
Lysine analogs & derivatives
Lysine metabolism
Male
Patch-Clamp Techniques methods
Potassium Channel Blockers pharmacology
Quinoxalines pharmacology
Rats
Rats, Long-Evans
Tetraethylammonium pharmacology
Valine analogs & derivatives
Valine pharmacology
Anticonvulsants pharmacology
CA1 Region, Hippocampal cytology
Inhibitory Postsynaptic Potentials drug effects
Neural Inhibition drug effects
Pyramidal Cells drug effects
Triazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1740-634X
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19776733
- Full Text :
- https://doi.org/10.1038/npp.2009.150