Phaclofen inhibition of the slow inhibitory postsynaptic potential in hippocampal slice cultures: A possible role for the GABAB-mediated inhibitory postsynaptic potential

A. T. Malouf, C. A. Robbins, Philip A Schwartzkroin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The GABAA antagonist bicuculline methiodide and the GABAB antagonist phaclofen were used to examine the function of the fast inhibitory postsynaptic potential and slow inhibitory postsynaptic potential, in hippocampal slice cultures in the rat. These cultures form easily-visualized monolayers of nerve cells which maintain the structure and synaptic organization of transverse hippocampal slices. The present study shows that the cellular and synaptic physiological properties of slice cultures are very similar, but not identical, to those observed in acutely-prepared hippocampal slices. The major difference is a higher incidence of fast excitatory postsynaptic potentials and inhibitory postsynaptic potentials compared to slices, and the appearance of spontaneous slow inhibitory postsynaptic potentials. This increase in synaptic drive has been useful for our investigation of the role of GABA-mediated inhibitory postsynaptic potentials. Bath application of 10 μM bicuculline blocked the fast inhibitory postsynaptic potentials and gave rise to bursts 1-11 s in duration. The presence of the slow inhibitory postsynaptic potentials did not prevent bicuculline-induced burst activity. Phaclofen (1 mM) perfused in the bath reversibly blocked the slow inhibitory postsynaptic potential, but did not result in the formation of large paroxysmal depolarizing shift-like bursts as seen with bicuculline. Rather, block of the slow inhibitory postsynaptic potential resulted in the formation of repetitive "afterdischarge bursts". These afterdischarge potentials typically appeared with a delay of 2-15 min following block of the slow inhibitory postsynaptic potential, during which time there was a gradual increase in non-synchronized excitatory activity. Once established, this cycle of increasing excitatory activity culminating in afterdischarge potentials recurred at 2-4 min intervals while phaclofen was present. These observations suggest that fast and slow inhibitory postsynaptic potentials serve different functions in the synaptic physiology of the hippocampus. While fast inhibitory postsynaptic potentials appear to limit the size of compound excitatory postsynaptic potentials and thereby prevent paroxysmal depolarizing shift-like epileptiform discharges, slow inhibitory postsynaptic potentials are ineffective at preventing such discharges. The primary function of the slow inhibitory postsynaptic potential appears to involve suppression of recurrent synaptic excitation which, if left undamped, can result in synchronization of excitatory activity and the formation of afterdischarge bursts.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalNeuroscience
Volume35
Issue number1
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

Inhibitory Postsynaptic Potentials
Bicuculline
Excitatory Postsynaptic Potentials
phaclofen
Baths
GABA-A Receptor Antagonists
gamma-Aminobutyric Acid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{bc1b3564586d441ea76241c81ab9f222,
title = "Phaclofen inhibition of the slow inhibitory postsynaptic potential in hippocampal slice cultures: A possible role for the GABAB-mediated inhibitory postsynaptic potential",
abstract = "The GABAA antagonist bicuculline methiodide and the GABAB antagonist phaclofen were used to examine the function of the fast inhibitory postsynaptic potential and slow inhibitory postsynaptic potential, in hippocampal slice cultures in the rat. These cultures form easily-visualized monolayers of nerve cells which maintain the structure and synaptic organization of transverse hippocampal slices. The present study shows that the cellular and synaptic physiological properties of slice cultures are very similar, but not identical, to those observed in acutely-prepared hippocampal slices. The major difference is a higher incidence of fast excitatory postsynaptic potentials and inhibitory postsynaptic potentials compared to slices, and the appearance of spontaneous slow inhibitory postsynaptic potentials. This increase in synaptic drive has been useful for our investigation of the role of GABA-mediated inhibitory postsynaptic potentials. Bath application of 10 μM bicuculline blocked the fast inhibitory postsynaptic potentials and gave rise to bursts 1-11 s in duration. The presence of the slow inhibitory postsynaptic potentials did not prevent bicuculline-induced burst activity. Phaclofen (1 mM) perfused in the bath reversibly blocked the slow inhibitory postsynaptic potential, but did not result in the formation of large paroxysmal depolarizing shift-like bursts as seen with bicuculline. Rather, block of the slow inhibitory postsynaptic potential resulted in the formation of repetitive {"}afterdischarge bursts{"}. These afterdischarge potentials typically appeared with a delay of 2-15 min following block of the slow inhibitory postsynaptic potential, during which time there was a gradual increase in non-synchronized excitatory activity. Once established, this cycle of increasing excitatory activity culminating in afterdischarge potentials recurred at 2-4 min intervals while phaclofen was present. These observations suggest that fast and slow inhibitory postsynaptic potentials serve different functions in the synaptic physiology of the hippocampus. While fast inhibitory postsynaptic potentials appear to limit the size of compound excitatory postsynaptic potentials and thereby prevent paroxysmal depolarizing shift-like epileptiform discharges, slow inhibitory postsynaptic potentials are ineffective at preventing such discharges. The primary function of the slow inhibitory postsynaptic potential appears to involve suppression of recurrent synaptic excitation which, if left undamped, can result in synchronization of excitatory activity and the formation of afterdischarge bursts.",
author = "Malouf, {A. T.} and Robbins, {C. A.} and Schwartzkroin, {Philip A}",
year = "1990",
doi = "10.1016/0306-4522(90)90119-O",
language = "English (US)",
volume = "35",
pages = "53--61",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Phaclofen inhibition of the slow inhibitory postsynaptic potential in hippocampal slice cultures

T2 - A possible role for the GABAB-mediated inhibitory postsynaptic potential

AU - Malouf, A. T.

AU - Robbins, C. A.

AU - Schwartzkroin, Philip A

PY - 1990

Y1 - 1990

N2 - The GABAA antagonist bicuculline methiodide and the GABAB antagonist phaclofen were used to examine the function of the fast inhibitory postsynaptic potential and slow inhibitory postsynaptic potential, in hippocampal slice cultures in the rat. These cultures form easily-visualized monolayers of nerve cells which maintain the structure and synaptic organization of transverse hippocampal slices. The present study shows that the cellular and synaptic physiological properties of slice cultures are very similar, but not identical, to those observed in acutely-prepared hippocampal slices. The major difference is a higher incidence of fast excitatory postsynaptic potentials and inhibitory postsynaptic potentials compared to slices, and the appearance of spontaneous slow inhibitory postsynaptic potentials. This increase in synaptic drive has been useful for our investigation of the role of GABA-mediated inhibitory postsynaptic potentials. Bath application of 10 μM bicuculline blocked the fast inhibitory postsynaptic potentials and gave rise to bursts 1-11 s in duration. The presence of the slow inhibitory postsynaptic potentials did not prevent bicuculline-induced burst activity. Phaclofen (1 mM) perfused in the bath reversibly blocked the slow inhibitory postsynaptic potential, but did not result in the formation of large paroxysmal depolarizing shift-like bursts as seen with bicuculline. Rather, block of the slow inhibitory postsynaptic potential resulted in the formation of repetitive "afterdischarge bursts". These afterdischarge potentials typically appeared with a delay of 2-15 min following block of the slow inhibitory postsynaptic potential, during which time there was a gradual increase in non-synchronized excitatory activity. Once established, this cycle of increasing excitatory activity culminating in afterdischarge potentials recurred at 2-4 min intervals while phaclofen was present. These observations suggest that fast and slow inhibitory postsynaptic potentials serve different functions in the synaptic physiology of the hippocampus. While fast inhibitory postsynaptic potentials appear to limit the size of compound excitatory postsynaptic potentials and thereby prevent paroxysmal depolarizing shift-like epileptiform discharges, slow inhibitory postsynaptic potentials are ineffective at preventing such discharges. The primary function of the slow inhibitory postsynaptic potential appears to involve suppression of recurrent synaptic excitation which, if left undamped, can result in synchronization of excitatory activity and the formation of afterdischarge bursts.

AB - The GABAA antagonist bicuculline methiodide and the GABAB antagonist phaclofen were used to examine the function of the fast inhibitory postsynaptic potential and slow inhibitory postsynaptic potential, in hippocampal slice cultures in the rat. These cultures form easily-visualized monolayers of nerve cells which maintain the structure and synaptic organization of transverse hippocampal slices. The present study shows that the cellular and synaptic physiological properties of slice cultures are very similar, but not identical, to those observed in acutely-prepared hippocampal slices. The major difference is a higher incidence of fast excitatory postsynaptic potentials and inhibitory postsynaptic potentials compared to slices, and the appearance of spontaneous slow inhibitory postsynaptic potentials. This increase in synaptic drive has been useful for our investigation of the role of GABA-mediated inhibitory postsynaptic potentials. Bath application of 10 μM bicuculline blocked the fast inhibitory postsynaptic potentials and gave rise to bursts 1-11 s in duration. The presence of the slow inhibitory postsynaptic potentials did not prevent bicuculline-induced burst activity. Phaclofen (1 mM) perfused in the bath reversibly blocked the slow inhibitory postsynaptic potential, but did not result in the formation of large paroxysmal depolarizing shift-like bursts as seen with bicuculline. Rather, block of the slow inhibitory postsynaptic potential resulted in the formation of repetitive "afterdischarge bursts". These afterdischarge potentials typically appeared with a delay of 2-15 min following block of the slow inhibitory postsynaptic potential, during which time there was a gradual increase in non-synchronized excitatory activity. Once established, this cycle of increasing excitatory activity culminating in afterdischarge potentials recurred at 2-4 min intervals while phaclofen was present. These observations suggest that fast and slow inhibitory postsynaptic potentials serve different functions in the synaptic physiology of the hippocampus. While fast inhibitory postsynaptic potentials appear to limit the size of compound excitatory postsynaptic potentials and thereby prevent paroxysmal depolarizing shift-like epileptiform discharges, slow inhibitory postsynaptic potentials are ineffective at preventing such discharges. The primary function of the slow inhibitory postsynaptic potential appears to involve suppression of recurrent synaptic excitation which, if left undamped, can result in synchronization of excitatory activity and the formation of afterdischarge bursts.

UR - http://www.scopus.com/inward/record.url?scp=0025286488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025286488&partnerID=8YFLogxK

U2 - 10.1016/0306-4522(90)90119-O

DO - 10.1016/0306-4522(90)90119-O

M3 - Article

C2 - 2359496

AN - SCOPUS:0025286488

VL - 35

SP - 53

EP - 61

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -