Homeostatic hippocampal activity against reduced glutamatergic neurotransmission

Tomoe Ishikawa, Kazuki Okamoto, Yuji Ikegaya

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Glutam ate mediates the majority of excitatory neurotransmission in the brain. Thus, blockade of non-NMDA-type receptors, the main type of ionotropic glutamate receptors under baseline conditions is expected to eliminate neuronal network activity. In the present work, we challenge this simple notion by showing the stability of spontaneous neuronal activity in cultured hippocampal networks in situ. We monitored spiking activity of hippocampal CA3 neuron populations by using a functional Multineuron Calcium Imaging (fMCI) technique. Bath application of competitive non-NMDA receptor antagonists decreased excitatory neurotransmission by approximately 80%. Surprisingly, however, it did not change the level of spontaneous network activity. The antagonists also reduced inhibitory synaptic inputs in CA3 pyramidal cells and thereby maintained the ratio between excitation and inhibition as a whole. Moreover, the antagonists induced an increase in the input resistance of CA3 pyramidal cells. These compensatoiy adaptations in excitability balance and neuronal intrinsic properties may provide ongoing network activity with homeostatic robustness against an external perturbation of non-NMDA receptors. Interestingly, the non-NMDA receptor antagonists reduced epilepsy-like synchronous hyperactivity to the normal activity level.

Original languageEnglish
Pages (from-to)318-326
Number of pages9
JournalInternational Journal of Pharmacology
Volume11
Issue number4
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Pyramidal Cells
Synaptic Transmission
Ionotropic Glutamate Receptors
Baths
Epilepsy
Calcium
Neurons
Brain
Population

Keywords

  • AMPA receptor
  • Homeostasis
  • Membrane resistance
  • Neuronal network
  • Spontaneous activity

ASJC Scopus subject areas

  • Pharmacology

Cite this

Homeostatic hippocampal activity against reduced glutamatergic neurotransmission. / Ishikawa, Tomoe; Okamoto, Kazuki; Ikegaya, Yuji.

In: International Journal of Pharmacology, Vol. 11, No. 4, 2015, p. 318-326.

Research output: Contribution to journalArticle

@article{737089b109d34cd3a2f0e5bf6681f3e9,
title = "Homeostatic hippocampal activity against reduced glutamatergic neurotransmission",
abstract = "Glutam ate mediates the majority of excitatory neurotransmission in the brain. Thus, blockade of non-NMDA-type receptors, the main type of ionotropic glutamate receptors under baseline conditions is expected to eliminate neuronal network activity. In the present work, we challenge this simple notion by showing the stability of spontaneous neuronal activity in cultured hippocampal networks in situ. We monitored spiking activity of hippocampal CA3 neuron populations by using a functional Multineuron Calcium Imaging (fMCI) technique. Bath application of competitive non-NMDA receptor antagonists decreased excitatory neurotransmission by approximately 80{\%}. Surprisingly, however, it did not change the level of spontaneous network activity. The antagonists also reduced inhibitory synaptic inputs in CA3 pyramidal cells and thereby maintained the ratio between excitation and inhibition as a whole. Moreover, the antagonists induced an increase in the input resistance of CA3 pyramidal cells. These compensatoiy adaptations in excitability balance and neuronal intrinsic properties may provide ongoing network activity with homeostatic robustness against an external perturbation of non-NMDA receptors. Interestingly, the non-NMDA receptor antagonists reduced epilepsy-like synchronous hyperactivity to the normal activity level.",
keywords = "AMPA receptor, Homeostasis, Membrane resistance, Neuronal network, Spontaneous activity",
author = "Tomoe Ishikawa and Kazuki Okamoto and Yuji Ikegaya",
year = "2015",
doi = "10.3923/iup.2015.318.326",
language = "English",
volume = "11",
pages = "318--326",
journal = "International Journal of Pharmacology",
issn = "1811-7775",
publisher = "Asian Network for Scientific Information",
number = "4",

}

TY - JOUR

T1 - Homeostatic hippocampal activity against reduced glutamatergic neurotransmission

AU - Ishikawa, Tomoe

AU - Okamoto, Kazuki

AU - Ikegaya, Yuji

PY - 2015

Y1 - 2015

N2 - Glutam ate mediates the majority of excitatory neurotransmission in the brain. Thus, blockade of non-NMDA-type receptors, the main type of ionotropic glutamate receptors under baseline conditions is expected to eliminate neuronal network activity. In the present work, we challenge this simple notion by showing the stability of spontaneous neuronal activity in cultured hippocampal networks in situ. We monitored spiking activity of hippocampal CA3 neuron populations by using a functional Multineuron Calcium Imaging (fMCI) technique. Bath application of competitive non-NMDA receptor antagonists decreased excitatory neurotransmission by approximately 80%. Surprisingly, however, it did not change the level of spontaneous network activity. The antagonists also reduced inhibitory synaptic inputs in CA3 pyramidal cells and thereby maintained the ratio between excitation and inhibition as a whole. Moreover, the antagonists induced an increase in the input resistance of CA3 pyramidal cells. These compensatoiy adaptations in excitability balance and neuronal intrinsic properties may provide ongoing network activity with homeostatic robustness against an external perturbation of non-NMDA receptors. Interestingly, the non-NMDA receptor antagonists reduced epilepsy-like synchronous hyperactivity to the normal activity level.

AB - Glutam ate mediates the majority of excitatory neurotransmission in the brain. Thus, blockade of non-NMDA-type receptors, the main type of ionotropic glutamate receptors under baseline conditions is expected to eliminate neuronal network activity. In the present work, we challenge this simple notion by showing the stability of spontaneous neuronal activity in cultured hippocampal networks in situ. We monitored spiking activity of hippocampal CA3 neuron populations by using a functional Multineuron Calcium Imaging (fMCI) technique. Bath application of competitive non-NMDA receptor antagonists decreased excitatory neurotransmission by approximately 80%. Surprisingly, however, it did not change the level of spontaneous network activity. The antagonists also reduced inhibitory synaptic inputs in CA3 pyramidal cells and thereby maintained the ratio between excitation and inhibition as a whole. Moreover, the antagonists induced an increase in the input resistance of CA3 pyramidal cells. These compensatoiy adaptations in excitability balance and neuronal intrinsic properties may provide ongoing network activity with homeostatic robustness against an external perturbation of non-NMDA receptors. Interestingly, the non-NMDA receptor antagonists reduced epilepsy-like synchronous hyperactivity to the normal activity level.

KW - AMPA receptor

KW - Homeostasis

KW - Membrane resistance

KW - Neuronal network

KW - Spontaneous activity

UR - http://www.scopus.com/inward/record.url?scp=84928045566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928045566&partnerID=8YFLogxK

U2 - 10.3923/iup.2015.318.326

DO - 10.3923/iup.2015.318.326

M3 - Article

AN - SCOPUS:84928045566

VL - 11

SP - 318

EP - 326

JO - International Journal of Pharmacology

JF - International Journal of Pharmacology

SN - 1811-7775

IS - 4

ER -