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Title: Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice
Authors: Cellot, Giada
Maggi, Laura
Di Castro, Maria Amalia
Catalano, Myriam
Migliore, Rosanna
Migliore, Michele
Scattoni, Maria Luisa
Calamandrei, Gemma
Cherubini, Enrico
First Published: 16-Aug-2016
Publisher: Nature Publishing Group
Citation: Scientific Reports, 2016, 6: 31696
Abstract: Coherent network oscillations (GDPs), generated in the immature hippocampus by the synergistic action of GABA and glutamate, both depolarizing and excitatory, play a key role in the construction of neuronal circuits. In particular, GDPs-associated calcium transients act as coincident detectors for enhancing synaptic efficacy at emerging GABAergic and glutamatergic synapses. Here, we show that, immediately after birth, in the CA3 hippocampal region of the BTBR T+tf/J mouse, an animal model of idiopathic autism, GDPs are severely impaired. This effect was associated with an increased GABAergic neurotransmission and a reduced neuronal excitability. In spite its depolarizing action on CA3 pyramidal cells (in single channel experiments EGABA was positive to Em), GABA exerted at the network level an inhibitory effect as demonstrated by isoguvacine-induced reduction of neuronal firing. We implemented a computational model in which experimental findings could be interpreted as the result of two competing effects: a reduction of the intrinsic excitability of CA3 principal cells and a reduction of the shunting activity in GABAergic interneurons projecting to principal cells. It is therefore likely that premature changes in neuronal excitability within selective hippocampal circuits of BTBR mice lead to GDPs dysfunction and behavioral deficits reminiscent of those found in autistic patients.
DOI Link: 10.1038/srep31696
eISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: In this Article, an affiliation has been omitted for Myriam Catalano. A Corrigendum is issued in Scientific Reports 7, Article number: 39726 (2017), doi:10.1038/srep39726 also archived
Appears in Collections:Published Articles, Dept. of Neuroscience, Psychology and Behaviour

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