Changes in stimuli and feeding in pregnant mothers alter the behavior of offspring. Since behavior is mediated by brain activity, it is expected that postnatal changes occur at the level of currents, receptors or soma and dendrites structure and modulation. In this work, we explore at the mechanism level the effects on Sprague–Dawley rat offspring following the administration of serotonin (5-HT) agonist 5-methoxytryptamine (5-MT). We analyzed whether 5-HT affects the glutamate-activated (I_Glut) and N-methyl-D-aspartate (NMDA)-activated currents (I_Glut, I_NMDA) in dissociated pyramidal neurons from the prefrontal cortex (PFC). For this purpose, we performed voltage-clamp experiments on pyramidal neurons from layers V-VI of the PFC of 40-day-old offspring born from 5-MT-treated mothers at the gestational days (GD) 11 to 21. We found that the pyramidal-neurons from the PFC of offspring of mothers treated with 5-MT exhibit a significant increased reduction in both the I_Glut and I_NMDA when 5-HT was administered. Our results suggest that the concentration increase of a neuromodulator during the gestation induces changes in its modulatory action over the offspring ionic currents during the adulthood thus contributing to possible psychiatric disorders.

Huntington’s Disease (HD) is a degenerative disease which produces cognitive and motor disturbances. Treatment with GABAergic agonists improves the behavior and activity of mitochondrial complexes in rodents treated with 3-nitropropionic acid to mimic HD symptomatology. Apparently, GABA receptors activity may protect striatal medium spiny neurons (MSNs) from excitotoxic damage. This study evaluates whether mitochondrial inhibition with 3-NP that mimics the early stages of HD, modifies the kinetics and pharmacology of GABA receptors in patch clamp recorded dissociated MSNs cells. The results show that MSNs from mice treated with 3-NP exhibited differences in GABA-induced dose-response currents and pharmacological responses that suggests the presence of GABA_C receptors in MSNs. Furthermore, there was a reduction in the effect of the GABA_C antagonist that demonstrates a lessening of this GABA receptor subtype activity as a result of mitochondria inhibition.

β-catenin-coding gene CTNNB1 is a top-ranking risk gene for autism and intellectual disability. To better understand how CTNNB1 haploinsufficiency is involved in the pathophysiology of neurodevelopmental disorders, we generated a new mouse model that enables Ctnnb1 deletion in forebrain excitatory neurons starting at embryonic corticogenesis. Behavioral assays of the Ctnnb1 conditional knockout (cKO) mice revealed significant fear memory deficits, despite normal social preference, anxiety, spatial and recognition memory. Pyramidal neurons in prefrontal cortex (PFC) of Ctnnb1 cKO mice exhibited the significantly elevated intrinsic excitability but markedly decreased AMPA receptor-mediated synaptic response, while GABAA or NMDA receptor-mediated synaptic response was unchanged. Gene profiling revealed the significantly reduced mRNA level of Syp (encoding Synaptophysin) and Nlng2 (encoding Neuroligin-2) in PFC of Ctnnb1 cKO mice, while most of other screened genes were unchanged. These results suggest that β-catenin deficiency in forebrain excitatory neurons leads to fear conditioning impairment, which could be contributed by the diminished excitatory synaptic transmission in PFC resulting from disrupted synaptic gene expression.