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The Journal of Neuroscience, July 2, 2008, 28(27):6974-6982; doi:10.1523/JNEUROSCI.4673-07.2008

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Cellular/Molecular
GABA_B Receptor Modulation of Feedforward Inhibition through Hippocampal Neurogliaform Cells

Christopher J. Price,^1 * Ricardo Scott,^2 * Dmitri A. Rusakov,² and Marco Capogna¹

¹Medical Research Council Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom, and ²Institute of Neurology, University College London, London WC1N 3BG, United Kingdom

Correspondence should be addressed to Dr. Marco Capogna, Medical Research Council Anatomical Neuropharmacology Unit, Mansfield Road, Oxford OX1 3TH, UK. Email: marco.capogna{at}pharm.ox.ac.uk

Feedforward inhibition of neurons is a fundamental component of information flow control in the brain. We studied the roles played by neurogliaform cells (NGFCs) of stratum lacunosum moleculare of the hippocampus in providing feedforward inhibition to CA1 pyramidal cells. We recorded from synaptically coupled pairs of anatomically identified NGFCs and CA1 pyramidal cells and found that, strikingly, a single presynaptic action potential evoked a biphasic unitary IPSC (uIPSC), consisting of two distinct components mediated by GABA_A and GABA_B receptors. A GABA_B receptor-mediated unitary response has not previously been observed in hippocampal excitatory neurons. The decay of the GABA_A receptor-mediated response was slow (time constant = 50 ms), and was tightly regulated by presynaptic GABA_B receptors. Surprisingly, the GABA_B receptor ligands baclofen and (2S)-3-{[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl}(phenylmethyl)phosphinic acid (CGP55845), while affecting the NGFC-mediated uIPSCs, had no effect on action potential-evoked presynaptic Ca²⁺ signals monitored in individual axonal boutons of NGFCs with two-photon microscopy. In contrast, baclofen clearly depressed presynaptic Ca²⁺ transients in non-NGF interneurons. Changes in extracellular Ca²⁺ concentration that mimicked the effects of baclofen or CGP55845 on uIPSCs significantly altered presynaptic Ca²⁺ transients. Electrophysiological data suggest that GABA_B receptors expressed by NGFCs contribute to the dynamic control of the excitatory input to CA1 pyramidal neurons from the temporoammonic path. The NGFC–CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells.

Key words: interneuron; synaptic transmission; GABA_B receptor; temporoammonic path; Ca²⁺ imaging; feedforward inhibition

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Received April 13, 2007; revised April 22, 2008; accepted May 15, 2008.

Correspondence should be addressed to Dr. Marco Capogna, Medical Research Council Anatomical Neuropharmacology Unit, Mansfield Road, Oxford OX1 3TH, UK. Email: marco.capogna{at}pharm.ox.ac.uk

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