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.
|Titolo:||Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice|
|Autori:||Cellot, Giada; Maggi, Laura; Di Castro, Maria Amalia; Catalano, Myriam; Migliore, Rosanna; Migliore, Michele; Scattoni, Maria Luisa; Calamandrei, Gemma; Cherubini, Enrico|
|Data di pubblicazione:||2016|
|Numero di Articolo:||31696|
|Digital Object Identifier (DOI):||10.1038/srep31696|
|Appare nelle tipologie:||1.1 Journal article|