Abstract
The hyperpolarization-activated cation current (IH) 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 IH in hippocampal CA1 pyramidal neurons, showing a potential anticonvulsant mechanism, as IH can dampen dendrito-somatic propagation of excitatory postsynaptic potentials in these cells. However, IH is also expressed in many hippocampal interneurons that provide synaptic inhibition to CA1 pyramidal neurons, and thus, IH modulation may indirectly regulate the inhibitory control of principal cells by direct modulation of interneuron activity. Whether IH 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 IH 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 μM) significantly increased IH 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 IH in CA1 interneurons can be increased by LTG, similarly to IH in pyramidal neurons, that IH enhancement increases interneuron excitability, and that these effects are associated with increased basal synaptic inhibition of CA1 pyramidal neurons.
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Acknowledgements
Images were generated in the Core Optical Imaging Facility, UTHSCSA. We thank Associate Director Victoria C Frohlich, PhD for her advice and assistance. This study was supported by NIH/NINDS R01 NS047385 (RMS); an Epilepsy Foundation of America Postdoctoral Research Training Fellowship, Chenguang Program of Wuhan city (No.200850731370), SRF for ROCS, SEM. (BWP); NSFC (No.30770734), Program for New Century Excellent Talents in University (No. NCET-07-0630) (XHH).
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Peng, BW., Justice, J., Zhang, K. et al. Increased Basal Synaptic Inhibition of Hippocampal Area CA1 Pyramidal Neurons by an Antiepileptic Drug that Enhances IH. Neuropsychopharmacol 35, 464–472 (2010). https://doi.org/10.1038/npp.2009.150
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DOI: https://doi.org/10.1038/npp.2009.150
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