Prenatal protein malnutrition results in increased frequency of miniature inhibitory synaptic currents in rat CA1 pyramidal cells

Abstract

There is growing evidence for an effect of prenatal protein malnutrition on the GABAergic neurotransmitter system in the rat hippocampus and associated structures. In the present study, we examined the functional electrophysiological consequences of observed alterations in GABA(A) and benzodiazepine receptor systems. Whole-cell patch clamp recordings of spontaneous and of miniature inhibitory postsynaptic currents (mIPSCs) generated by CA1 pyramidal cells were performed in in vitro hippocampal slices prepared from control and prenatally protein malnourished adult male rats. The characteristics of spontaneous synaptic currents were unaltered by the prenatal insult, as were the amplitudes and kinetics of GABA(A) receptor-mediated mIPSCs. The frequency of mIPSCs, however, was significantly increased in CA1 pyramidal cells in slices prepared from prenatally malnourished vs. control rats. The effect of the benzodiazepine receptor agonist chlordiazepoxide on the characteristics of mIPSCs was also examined and found to be the same in cells from both nutritional groups. The increased frequency of mIPSCs together with the lack of a change in amplitude, kinetics, or modulation by benzodiazepines of mIPSCs in response to prenatal protein malnutrition indicate a presynaptic locus of effect of this insult.

Neonatal low-protein diet reduces the masticatory efficiency in rats

“…Undernutrition has also been shown to affect the γ-aminobutyric acid (GABA)ergic system in several ways (i.e. in the number of GABAergic neurons ( 73 ) , the composition and sensitivity of GABAergic receptors ( 67 , 71 ) and the frequency of miniature inhibitory post-synaptic currents ( 74 ) ). In a recent study, protein deficiency was associated with reduced sensory processing and a substantial increase in GAD65 neurons in the whisker barrel cortex ( 63 ) .…”

Early-Life Nutritional Programming of Cognition—The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process

“…Afferents from the raphe nuclei, the locus coeruleus, and the medial septum synapse onto intermediate g-aminobutyric acid (GABA) neurons, which then project to the hippocampus. Previous studies have indicated that prenatal protein malnutrition enhances GABAergic inputs to the hippocampus and suggest that altered GABAergic function may be caused by changes in serotonergic inputs (13,14). Indeed, protein-restricted rats showed a downregulation in the serotonin fiber density and uptake sites in the dentate gyrus and cornu ammonis 3 (15).…”

The neural basis of attentional alterations in prenatally protein malnourished rats

“…Prior work with this model has shown that prenatal protein malnutrition produces specific effects on the structure and function of the hippocampus and specifically affects inhibitory networks and neuroplastic mechanisms such as long-term potentiation (e.g., Diáz-Cintra et al, 1991, 1994Bronzino et al, 1997;Rushmore et al, 1998;Luebke et al, 2000;Morgane et al, 2002;Chang et al, 2003;Lister et al, 2005). While some hippocampallymediated behaviors show clear differences in 25/25 vs. 6/25 rats, other behaviors commonly associated with an intact hippocampal formation, such as spatial navigation and working memory, showed little difference in the prenatally malnourished animals (Morgane et al, 2002), suggesting prenatally malnourished animals may be able to compensate for changes in hippocampal structure and function.…”