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Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain.

Publication ,  Journal Article
Tu, B; Timofeeva, O; Jiao, Y; Nadler, JV
Published in: J Neurosci
February 16, 2005

In the pilocarpine model of temporal lobe epilepsy, mossy fibers coexpress the inhibitory transmitter neuropeptide Y (NPY) with glutamate. The effects of endogenous and applied NPY on recurrent mossy fiber synaptic transmission were investigated with the use of whole-cell voltage-clamp and field recordings in rat hippocampal slices. Applied NPY reversibly inhibited synaptic transmission at recurrent mossy fiber synapses on dentate granule cells but not at perforant path or associational-commissural synapses. It also reduced the frequency of miniature EPSCs (mEPSCs) in granule cells from epileptic, but not control, rats and depressed granule cell epileptiform activity dependent on the recurrent mossy fiber pathway. These actions of NPY were mediated by activation of presynaptic Y2 receptors. The Y2 receptor antagonist (S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]argininamide (BIIE0246) not only blocked the effects of NPY but also enhanced recurrent mossy fiber synaptic transmission, the frequency of mEPSCs, and the magnitude of mossy fiber-evoked granule cell epileptiform activity when applied by itself. Several observations supported the selectivity of BIIE0246. These results suggest that even the spontaneous release of NPY (or an active metabolite) from recurrent mossy fibers is sufficient to depress glutamate release from this pathway. Tonic release of NPY accounts at least partially for the low probability of glutamate release from recurrent mossy fiber terminals, impedes the ability of these fibers to synchronize granule cell discharge, and may protect the hippocampus from seizures that involve the entorhinal cortex. This pathway may synchronize granule cell discharge more effectively in human brain than in rat because of its lower expression of NPY.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

February 16, 2005

Volume

25

Issue

7

Start / End Page

1718 / 1729

Location

United States

Related Subject Headings

  • Tetrodotoxin
  • Synaptic Transmission
  • Status Epilepticus
  • Receptors, Neuropeptide Y
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Pilocarpine
  • Perforant Pathway
  • Patch-Clamp Techniques
 

Citation

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Tu, B., Timofeeva, O., Jiao, Y., & Nadler, J. V. (2005). Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain. J Neurosci, 25(7), 1718–1729. https://doi.org/10.1523/JNEUROSCI.4835-04.2005
Tu, Bin, Olga Timofeeva, Yiqun Jiao, and J Victor Nadler. “Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain.J Neurosci 25, no. 7 (February 16, 2005): 1718–29. https://doi.org/10.1523/JNEUROSCI.4835-04.2005.
Tu, Bin, et al. “Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain.J Neurosci, vol. 25, no. 7, Feb. 2005, pp. 1718–29. Pubmed, doi:10.1523/JNEUROSCI.4835-04.2005.
Tu B, Timofeeva O, Jiao Y, Nadler JV. Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain. J Neurosci. 2005 Feb 16;25(7):1718–1729.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

February 16, 2005

Volume

25

Issue

7

Start / End Page

1718 / 1729

Location

United States

Related Subject Headings

  • Tetrodotoxin
  • Synaptic Transmission
  • Status Epilepticus
  • Receptors, Neuropeptide Y
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Pilocarpine
  • Perforant Pathway
  • Patch-Clamp Techniques