Variable Dendritic Integration in Hippocampal CA3 Pyramidal Neurons

The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons....

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Published inNeuron (Cambridge, Mass.) Vol. 80; no. 6; pp. 1438 - 1450
Main Authors Makara, Judit K., Magee, Jeffrey C.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 18.12.2013
Elsevier Limited
Cell Press
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Abstract The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K+ current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry. •Active nonlinear dendritic integration in CA3 pyramidal neurons•NMDARs mediate amplification of synchronous synaptic inputs•Compartmentalized control of dendritic integration and somatic output by K+ channels Makara and Magee demonstrate NMDA receptor-mediated supralinear dendritic integration of multiple coactive synaptic inputs in thin dendrites of hippocampal CA3 pyramidal neurons and reveal a powerful regulation of these NMDA spikes by G-protein-activated inwardly rectifying K+ channels.
AbstractList The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K + current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry. • Active nonlinear dendritic integration in CA3 pyramidal neurons • NMDARs mediate amplification of synchronous synaptic inputs • Compartmentalized control of dendritic integration and somatic output by K+ channels Makara and Magee demonstrate NMDA receptor-mediated supralinear dendritic integration of multiple coactive synaptic inputs in thin dendrites of hippocampal CA3 pyramidal neurons and reveal a powerful regulation of these NMDA spikes by G-protein-activated inwardly rectifying K+ channels.
The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K+ current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry.
The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K+ current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry. •Active nonlinear dendritic integration in CA3 pyramidal neurons•NMDARs mediate amplification of synchronous synaptic inputs•Compartmentalized control of dendritic integration and somatic output by K+ channels Makara and Magee demonstrate NMDA receptor-mediated supralinear dendritic integration of multiple coactive synaptic inputs in thin dendrites of hippocampal CA3 pyramidal neurons and reveal a powerful regulation of these NMDA spikes by G-protein-activated inwardly rectifying K+ channels.
The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of ensembles of CA3 pyramidal neurons produces spatiotemporally structured input patterns arriving onto dendrites of recurrently connected CA3 neurons. To understand how such input patterns are translated into specific output patterns, we characterized dendritic integration in CA3 pyramidal cells using two-photon imaging and glutamate uncaging. We found that thin dendrites of CA3 pyramidal neurons integrate synchronous synaptic input in a highly supralinear fashion. The amplification was primarily mediated by NMDA receptor activation and was present over a relatively broad range of spatiotemporal input patterns. The decay of voltage responses, temporal summation, and action potential output was regulated in a compartmentalized fashion mainly by a G-protein-activated inwardly rectifying K(+) current. Our results suggest that plastic dendritic integrative mechanisms may support ensemble behavior in pyramidal neurons of the hippocampal circuitry.
Author Makara, Judit K.
Magee, Jeffrey C.
AuthorAffiliation 2 Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA
1 Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary
AuthorAffiliation_xml – name: 1 Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary
– name: 2 Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA
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  surname: Makara
  fullname: Makara, Judit K.
  email: makara.judit@koki.mta.hu
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– sequence: 2
  givenname: Jeffrey C.
  surname: Magee
  fullname: Magee, Jeffrey C.
  organization: Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24360546$$D View this record in MEDLINE/PubMed
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Snippet The hippocampal CA3 region is essential for pattern completion and generation of sharp-wave ripples. During these operations, coordinated activation of...
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SubjectTerms Action Potentials - physiology
Animals
Brain
CA3 Region, Hippocampal - physiology
Dendrites - physiology
Experiments
G Protein-Coupled Inwardly-Rectifying Potassium Channels - physiology
Glutamic Acid - pharmacology
Male
N-Methylaspartate - physiology
Neurons
Potassium Channels
Pyramidal Cells - physiology
Rats
Sodium - physiology
Title Variable Dendritic Integration in Hippocampal CA3 Pyramidal Neurons
URI https://dx.doi.org/10.1016/j.neuron.2013.10.033
https://www.ncbi.nlm.nih.gov/pubmed/24360546
https://www.proquest.com/docview/1551721144
https://search.proquest.com/docview/1490740197
https://search.proquest.com/docview/1516739505
https://pubmed.ncbi.nlm.nih.gov/PMC3878388
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