Chronic Loss of CA2 Transmission Leads to Hippocampal Hyperexcitability

Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility a...

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Vydané v:Neuron (Cambridge, Mass.) Ročník 94; číslo 3; s. 642
Hlavní autori: Boehringer, Roman, Polygalov, Denis, Huang, Arthur J Y, Middleton, Steven J, Robert, Vincent, Wintzer, Marie E, Piskorowski, Rebecca A, Chevaleyre, Vivien, McHugh, Thomas J
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 03.05.2017
Predmet:
Animals
CA2 Region, Hippocampal - cytology
CA2 Region, Hippocampal - physiology
CA3 Region, Hippocampal - cytology
CA3 Region, Hippocampal - physiology
Hippocampus - physiology
Metalloendopeptidases - genetics
Metalloendopeptidases - metabolism
Mice
Nerve Net - physiology
Neural Inhibition - physiology
Pyramidal Cells - physiology
Synaptic Transmission - physiology
Tetanus Toxin - genetics
Tetanus Toxin - metabolism
Theta Rhythm - physiology
theta oscillation
CA3
hippocampus
ripple
CA2
spatial coding
DREADD
tetanus toxin
place cell
ISSN:1097-4199, 1097-4199
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Popis
Shrnutí:Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility and generating ripple oscillations, an interventional examination of the integrative functions of these connections has yet to be reported. Here we demonstrate that CA2 recruits feedforward inhibition in CA3 and that chronic genetically engineered shutdown of CA2-pyramidal-cell synaptic transmission consequently results in increased excitability of the recurrent CA3 network. In behaving mice, this led to spatially triggered episodes of network-wide hyperexcitability during exploration accompanied by the emergence of high-frequency discharges during rest. These findings reveal CA2 as a regulator of network processing in hippocampus and suggest that CA2-mediated inhibition in CA3 plays a key role in establishing the dynamic excitatory and inhibitory balance required for proper network function.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4199
1097-4199
DOI:10.1016/j.neuron.2017.04.014