Substance P Enhances NMDA Channel Function in Hippocampal Dentate Gyrus Granule Cells

Lieberman, David N. and Istvan Mody. Substance P enhances NMDA channel function in hippocampal dentate gyrus granule cells. J. Neurophysiol. 80: 113–119, 1998. Substance P (SP)–containing afferents and the NK-1 tachykinin receptor to which SP binds are present in the dentate gyrus of the rat; however, direct actions of SP on principal cells have not been demonstrated in this brain region. We have examined the effect of SP on N-methyl-d-aspartate (NMDA) channels from acutely isolated dentate gyrus granule cells of adult rat hippocampus to assess the ability of SP to regulate glutamatergic input. SP produces a robust enhancement of single NMDA channel function that is mimicked by the NK-1–selective agonist Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is prevented by the selective NK-1 receptor antagonist (+)-(2 S,3 S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation of protein kinase C were not required for the SP-induced increase in NMDA channel open durations. The dramatic enhancement of excitatory amino acid–mediated excitability by SP places this neuropeptide in a key position to gate activation of hippocampal network activity.

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Quantitative analysis of the dendritic branching pattern of granule cells from adult rat dentate gyrus

Experimental Neurology ◽

10.1016/0014-4886(81)90062-5 ◽

1981 ◽

Vol 73 (1) ◽

pp. 286-297 ◽

Cited By ~ 14

Author(s):

Robert D. Lindsay ◽

Arnold B. Scheibel

Keyword(s):

Quantitative Analysis ◽

Dentate Gyrus ◽

Granule Cells ◽

Branching Pattern ◽

Adult Rat ◽

Dendritic Branching

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Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells

Journal of Neurophysiology ◽

10.1152/jn.2002.87.5.2624 ◽

2002 ◽

Vol 87 (5) ◽

pp. 2624-2628 ◽

Cited By ~ 325

Author(s):

Zoltan Nusser ◽

Istvan Mody

Keyword(s):

Dentate Gyrus ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Hippocampal Slices ◽

Tonic Inhibition ◽

Adult Rats ◽

Adult Rat ◽

Phasic Inhibition ◽

The Mean

In some nerve cells, activation of GABAA receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABAA receptors with a specific subunit composition (α6βxδ). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in δ subunit–expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of ∼10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 μM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 μM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABAA receptor–mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.

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