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Sunday, June 17, 2012

Effects of third trimester-equivalent ethanol exposure on Cl− co-transporter expression, network activity, and GABAergic transmission in the CA3 hippo

Fetal alcohol spectrum disorders are often associated with structural and functional hippocampal abnormalities, leading to long-lasting learning and memory deficits. The mechanisms underlying these abnormalities are not fully understood.

Here, we investigated whether ethanol exposure during the 3rd trimester-equivalent period alters spontaneous network activity that is involved in neuronal circuit development in the CA3 hippocampal region. This activity is driven by GABA
A receptors, which can have excitatory actions in developing neurons as a consequence of greater expression of the Cl importer, NKCC1, with respect to expression of the Cl exporter, KCC2, resulting in high [Cl]i.

Rat pups were exposed to ethanol vapor from postnatal day (P) 2–16 (4 h/day).

Weight gain was significantly reduced in pups exposed to ethanol compared to control at P15 and 16. Brain slices were prepared immediately after the end of the 4-h exposure on P4-16 and experiments were also performed under ethanol-free conditions at the end of the exposure paradigm (P17-22).

Ethanol exposure did not significantly affect expression of KCC2 or NKCC1, nor did it affect network activity in the CA3 hippocampal region. Ethanol exposure significantly decreased the frequency (at P9-11) and increased the amplitude (at P5-8 and P17-21) of GABA
A receptor-mediated miniature postsynaptic currents.

These data suggest that repeated
in vivo exposure to ethanol during the 3rd trimester-equivalent period alters GABAergic transmission in the CA3 hippocampal region, an effect that could lead to abnormal circuit maturation and perhaps contribute to the pathophysiology of fetal alcohol spectrum disorders.

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