Bi-directional modulation of fast inhibitory synaptic transmission by leptin

Natasha Solovyova, Peter R. Moult, Bogdan Milojkovic, Jeremy J. Lambert, Jenni Harvey

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABA(A) receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABA(A) receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABA(A) receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability.

    Original languageEnglish
    Pages (from-to)190-201
    Number of pages12
    JournalJournal of Neurochemistry
    Volume108
    Issue number1
    DOIs
    Publication statusPublished - Jan 2009

    Keywords

    • Akt
    • inhibitory long-lasting depression
    • inhibitory synaptic transmission
    • leptin
    • PI 3 kinase
    • LONG-TERM POTENTIATION
    • FUNCTIONAL GABA(A) RECEPTORS
    • HIPPOCAMPAL PYRAMIDAL CELLS
    • ARCUATE NUCLEUS NEURONS
    • GABAERGIC SYNAPSES
    • FEEDING CIRCUITS
    • DYNAMIC CHANGES
    • CA1 NEURONS
    • BK CHANNELS
    • INSULIN

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