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The Journal of Neuroscience, November 8, 2006, 26(45):11720-11725; doi:10.1523/JNEUROSCI.2887-06.2006

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Cellular/Molecular
GABAergic Input onto CA3 Hippocampal Interneurons Remains Shunting throughout Development

Tue G. Banke and Chris J. McBain

Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Correspondence should be addressed to Chris J. McBain, Laboratory of Cellular and Synaptic Neurophysiology, Building 35, Room 3C903, National Institute of Child Health and Human Development–Laboratory of Cellular and Synaptic Neurophysiology, Bethesda, MD 20892. Email: mcbainc{at}mail.nih.gov

In hippocampus, the net flow of excitability is controlled by inhibitory input provided by the many populations of local circuit inhibitory interneurons. In principal cells, GABAA receptor-mediated synaptic input undergoes a highly coordinated shift from depolarizing early in life to a more conventional hyperpolarizing inhibition on maturation. This switch in inhibitory input polarity is controlled by the developmental regulation of two chloride cotransporters (NKCC1 and KCC2) that results in a net shift from high to low intracellular Cl. Whether inhibitory input onto inhibitory interneurons demonstrates a similar developmental shift in intracellular Cl is unexplored. Using the gramicidin perforated-patch configuration, we recorded from CA3 hippocampal stratum lucidum interneurons and pyramidal cells to monitor inhibitory input across a broad developmental range. GABAA receptor-mediated synaptic input onto stratum lucidum inhibitory interneurons was shunting in nature across the entire developmental age range tested, as resting membrane potential and the IPSC reversal potential remained within a few millivolts (1–4 mV) between postnatal day 5 (P5) and P31. Furthermore, sensitivity to block of the two chloride cotransporters KCC2 and NKCC1 did not differ across the same age range, suggesting that their relative expression is fixed across development. In contrast, pyramidal cell synaptic inhibition demonstrated the well described switch from depolarizing to hyperpolarizing over the same age range. Thus, in contrast to principal cells, inhibitory synaptic input onto CA3 interneurons remains shunting throughout development.

Key words: GABA; synaptic inhibition; hippocampus; interneurons; development; CA3


Received July 7, 2006; revised Oct. 4, 2006; accepted Oct. 4, 2006.

Correspondence should be addressed to Chris J. McBain, Laboratory of Cellular and Synaptic Neurophysiology, Building 35, Room 3C903, National Institute of Child Health and Human Development–Laboratory of Cellular and Synaptic Neurophysiology, Bethesda, MD 20892. Email: mcbainc{at}mail.nih.gov




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