- Restoring GABA tone rescues hippocampal long-term depression impaired after maternal immune stress doi link

Auteur(s): Barbanel G.

Conference: “Development, Functions and Disorders of the Nervous System” (Montreal, CA, 2014-07-19)

Ref HAL: hal-01226761_v1
DOI: 10.1016/j.ijdevneu.2015.04.105

Rat maternal immune challenge with lipopolysaccharide (LPS) led to an early disturbance of glutamatergic synaptic plasticity in the hippocampus of male offspring (Lanté et al., 2007, 2008). This was evidenced by a premature loss of the ability to exhibit long-term depression (LTD) (Escobar et al., 2011), which occurred between the second and the third postnatal weeks instead of after the first postnatal month. We hypothesized this would be related to GABAergic system deficiency.Sprague Dawley rats received either 500 μg kg−1 LPS or 2 ml kg−1 isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between postnatal days 12–25. GABAergic interneuron density was determined by stereology. GABAergic transmission and the effect of tiagabine on glutamatergic synaptic plasticity were assessed with patch clamp and extracellular recordings respectively.Prenatal LPS triggered a clear deficit of GABAergic interneurons predominant in the CA3 area of the hippocampus, associated with presynaptic GABAergic transmission deficiency, as shown by reduced evoked inhibitory post synaptic currents and by a reduction of the frequency of miniature post synaptic currents. Of note, GABAA and GABAB receptors and GABA transporters appeared mainly unaffected.Increasing ambient GABA by impairing GABA re-uptake with tiagabine did not interact with the occurrence of LTD in normal animals in this developmental window, but rescued the impaired synaptic plasticity observed in LPS-challenged rats.Deficiency in tonic actions of GABA seems to be central to the dysregulation of synaptic plasticity observed after immune prenatal challenge. Modulating GABAergic tone may be a valuable therapeutic strategy for the cognitive impairment associated with this condition.