Hyperpolarizing and depolarizing GABA(A) receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus

Nevin A Lambert, A. M. Borroni, L. M. Grover, T. J. Teyler

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

1. γ-Aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7- dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30 μM) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-](o)) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4- aminopyridine (50-100 μM), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.

Original languageEnglish (US)
Pages (from-to)1538-1548
Number of pages11
JournalJournal of Neurophysiology
Volume66
Issue number5
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Fingerprint

Inhibitory Postsynaptic Potentials
GABA-A Receptors
Hippocampus
gamma-Aminobutyric Acid
GABA-B Receptors
Pyramidal Cells
Excitatory Postsynaptic Potentials
Dendrites
GABA-B Receptor Antagonists
Population
2-Amino-5-phosphonovalerate
Aminobutyrates
GABA-A Receptor Antagonists
Excitatory Amino Acid Antagonists
4-Aminopyridine
Glutamate Receptors
Evoked Potentials
Electric Stimulation
Chlorides
Pressure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Hyperpolarizing and depolarizing GABA(A) receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus. / Lambert, Nevin A; Borroni, A. M.; Grover, L. M.; Teyler, T. J.

In: Journal of Neurophysiology, Vol. 66, No. 5, 01.01.1991, p. 1538-1548.

Research output: Contribution to journalArticle

@article{8c4dce8aa2094720959f8a548255e0d2,
title = "Hyperpolarizing and depolarizing GABA(A) receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus",
abstract = "1. γ-Aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7- dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30 μM) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-](o)) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4- aminopyridine (50-100 μM), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.",
author = "Lambert, {Nevin A} and Borroni, {A. M.} and Grover, {L. M.} and Teyler, {T. J.}",
year = "1991",
month = "1",
day = "1",
doi = "10.1152/jn.1991.66.5.1538",
language = "English (US)",
volume = "66",
pages = "1538--1548",
journal = "Journal of Neurophysiology",
issn = "0022-3077",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Hyperpolarizing and depolarizing GABA(A) receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus

AU - Lambert, Nevin A

AU - Borroni, A. M.

AU - Grover, L. M.

AU - Teyler, T. J.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - 1. γ-Aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7- dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30 μM) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-](o)) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4- aminopyridine (50-100 μM), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.

AB - 1. γ-Aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7- dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30 μM) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-](o)) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4- aminopyridine (50-100 μM), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.

UR - http://www.scopus.com/inward/record.url?scp=0026357486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026357486&partnerID=8YFLogxK

U2 - 10.1152/jn.1991.66.5.1538

DO - 10.1152/jn.1991.66.5.1538

M3 - Article

C2 - 1684989

AN - SCOPUS:0026357486

VL - 66

SP - 1538

EP - 1548

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 5

ER -