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Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice

journal contribution
posted on 24.08.2017, 15:12 by Giada Cellot, Laura Maggi, Maria Amalia Di Castro, Myriam Catalano, Rosanna Migliore, Michele Migliore, Maria Luisa Scattoni, Gemma Calamandrei, Enrico Cherubini
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.

History

Citation

Scientific Reports, 2016, 6: 31696

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

Scientific Reports

Publisher

Nature Publishing Group

eissn

2045-2322

Acceptance date

27/07/2016

Copyright date

2016

Available date

24/08/2017

Publisher version

https://www.nature.com/articles/srep31696

Notes

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 http://hdl.handle.net/2381/41931

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en

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