Li+ enhances GABAergic inputs to granule cells in the rat hippocampal dentate gyrus.
Defects in GABAergic interneurons are thought to be involved in the pathophysiology of bipolar disorder, and Li+ has been used as a primary therapeutic agent in the treatment. We used the patch clamp technique to investigate whether Li+ affects on spontaneous GABAergic synaptic inputs to granule cells (GCs) in hippocampal dentate gyrus. Extracellularly applied Li+ (25 mM) markedly increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs), an effect completely blocked by picrotoxin or bicuculline. Li+ increased sIPSCs frequency in the presence of tetrodotoxin (TTX), but to a lesser extent than its absence. Li+ caused no change in the cumulative amplitude distribution of miniature IPSCs, indicating that a presynaptic mechanism is involved. When TTX was added in the presence of Li+, large-amplitude sIPSCs (>30 pA) were abolished specifically with no effect on small-amplitude sIPSCs (<20 pA). Intracellular Li+ (6 mM) applied via the patch pipette depolarized the resting membrane potential in fast-spiking interneurons, resulting in an increase in spontaneous action potential (AP) firing. This change, however, was not observed in GCs. These results suggest that Li(+)-induced spontaneous AP firing in GABAergic interneurons contributes to the increase in GABAergic synaptic inputs to GCs.
Department of Physiology, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Ku, Seoul 110-799, South Korea.
Suk-Ho
SH
Lee
Jong-Woo
JW
Sohn
Seung-Cheol
SC
Ahn
Won-Sun
WS
Park
Won-Kyung
WK
Ho
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D018021:Lithium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D018021:Lithium Chloride