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AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons.
Neuroscience. 2005; 135(2):555-67.N

Abstract

Positive modulators of AMPA receptors enhance synaptic plasticity and memory encoding. Facilitation of AMPA receptor currents not only results in enhanced activation of excitatory neurons but also increases the activity of inhibitory interneurons by up-modulating their excitatory input. However, little is known about the effects of these modulators on cells other than pyramidal neurons and about their impact on local microcircuits. This study examined the effects of members from three subfamilies of modulators (mainly CX516, CX546 and cyclothiazide) on excitatory synaptic responses in four classes of hippocampal CA1 neurons and on excitatory and disynaptically induced inhibitory field potentials in hippocampal slices. Effects on excitatory postsynaptic currents (EPSCs) were examined in pyramidal cells, in two types of inhibitory interneurons located in stratum radiatum and oriens, and in stratum radiatum giant cells, a novel type of excitatory neuron. With CX516, increases in EPSC amplitude in pyramidal cells were two to three times larger than in interneurons and six times larger than in radiatum giant cells. The effects of CX546 on response duration similarly were largest in pyramidal cells. However, this drug also strongly differentiated between stratum oriens and radiatum interneurons with increases being four times larger in the latter. In contrast, cyclothiazide had similar effects on response duration in all cell types. In field recordings, CX516 was several times more potent in enhancing excitatory postsynaptic potentials (EPSPs) than feedback or feedforward circuits, as expected from its larger influence on pyramidal cells. In contrast, BDP-20, a CX546 analog, was more potent in enhancing feedforward inhibition than either EPSPs or feedback inhibition. This preference for feedforward over feedback circuits is probably related to its higher potency in stratum radiatum versus oriens interneurons. Taken together, AMPA receptor modulators differ substantially in their potency and/or efficacy across major classes of neurons which is likely to have consequences with regard to their impact on circuits and behavior.

Authors+Show Affiliations

Department of Pharmacology, Southern Illinois University, School of Medicine, PO Box 19629, Springfield, IL 62794-9629, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16125852

Citation

Xia, Y-F, and A C. Arai. "AMPA Receptor Modulators Have Different Impact On Hippocampal Pyramidal Cells and Interneurons." Neuroscience, vol. 135, no. 2, 2005, pp. 555-67.
Xia YF, Arai AC. AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons. Neuroscience. 2005;135(2):555-67.
Xia, Y. F., & Arai, A. C. (2005). AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons. Neuroscience, 135(2), 555-67.
Xia YF, Arai AC. AMPA Receptor Modulators Have Different Impact On Hippocampal Pyramidal Cells and Interneurons. Neuroscience. 2005;135(2):555-67. PubMed PMID: 16125852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons. AU - Xia,Y-F, AU - Arai,A C, PY - 2005/04/05/received PY - 2005/06/03/revised PY - 2005/06/15/accepted PY - 2005/8/30/pubmed PY - 2006/1/26/medline PY - 2005/8/30/entrez SP - 555 EP - 67 JF - Neuroscience JO - Neuroscience VL - 135 IS - 2 N2 - Positive modulators of AMPA receptors enhance synaptic plasticity and memory encoding. Facilitation of AMPA receptor currents not only results in enhanced activation of excitatory neurons but also increases the activity of inhibitory interneurons by up-modulating their excitatory input. However, little is known about the effects of these modulators on cells other than pyramidal neurons and about their impact on local microcircuits. This study examined the effects of members from three subfamilies of modulators (mainly CX516, CX546 and cyclothiazide) on excitatory synaptic responses in four classes of hippocampal CA1 neurons and on excitatory and disynaptically induced inhibitory field potentials in hippocampal slices. Effects on excitatory postsynaptic currents (EPSCs) were examined in pyramidal cells, in two types of inhibitory interneurons located in stratum radiatum and oriens, and in stratum radiatum giant cells, a novel type of excitatory neuron. With CX516, increases in EPSC amplitude in pyramidal cells were two to three times larger than in interneurons and six times larger than in radiatum giant cells. The effects of CX546 on response duration similarly were largest in pyramidal cells. However, this drug also strongly differentiated between stratum oriens and radiatum interneurons with increases being four times larger in the latter. In contrast, cyclothiazide had similar effects on response duration in all cell types. In field recordings, CX516 was several times more potent in enhancing excitatory postsynaptic potentials (EPSPs) than feedback or feedforward circuits, as expected from its larger influence on pyramidal cells. In contrast, BDP-20, a CX546 analog, was more potent in enhancing feedforward inhibition than either EPSPs or feedback inhibition. This preference for feedforward over feedback circuits is probably related to its higher potency in stratum radiatum versus oriens interneurons. Taken together, AMPA receptor modulators differ substantially in their potency and/or efficacy across major classes of neurons which is likely to have consequences with regard to their impact on circuits and behavior. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16125852/AMPA_receptor_modulators_have_different_impact_on_hippocampal_pyramidal_cells_and_interneurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(05)00702-5 DB - PRIME DP - Unbound Medicine ER -