Brittany A. Davis's research while affiliated with Lieber Institute for Brain Development and other places

... Lastly, we determined if the reduction in IN density was reflected in the balance of excitatory and inhibitory inputs onto pyramidal cells in the mPFC. Prior studies of both human and mouse models of PTHS have reported a reduction in spontaneous excitatory synaptic transmission and excitatory synapses [49][50][51][52]. Consistent with these prior results, we observed that pyramidal neurons in brain slices from Tcf4 +/tr mice showed a significant reduction in the frequency and amplitude of sEPSCs compared to WT pyramidal cells (Fig. 7A). ...

... An mRuby fluorescence reference image and a time-series of GFP were acquired at 4 Hz for 8 min for each well. Analysis was conducted using the CapTure pipeline [40]. T-test was used to calculate p-values listed in all figures. ...

... This is in line with the ndings of Benevento et al., who showed that BDNF levels were abnormally increased in the brain of Ehmt1 +/− mice due to hypomethylation of the BDNF promoter 38 . Similarly, in Ehmt1 +/− mouse embryonic stem cell-derived neurons Bdnf was repressed by NRSF/REST and loss of Ehmt1 by reducing the expression of NRSF/REST resulted in increased expression of REST-target genes, among them Bdnf 39 . We further investigated the synapthogenesis but the increase in neurite outgrowth did not lead to higher connectivity within neuronal networks as assessed by the lower expression of PSD-95 and SYNP in the KS line. ...

... EHMT1 −/+ mice demonstrate cranial abnormalities, hypotonia and delayed postnatal growth [18]. Functionally they show deficits in fear extinction and novel object recognition [18][19][20][21]. In rodent primary neuron cultures EHMT1 regulates the dynamics of multiple neural processes, including synaptic scaling and response to addiction and stress [20,22] and knockdown of Ehmt1 or the other KSS associated genes alter synaptic gene regulation and neuronal excitability. ...

... Nakashima et al. similarly concluded that a high PI was significantly associated with the development of ASD. Phan et al. [32] found that preoperative PT and PI-LL were larger, while SS and LL were smaller in patients with postoperative ASD compared to controls, indicating significant correlations between changes in sagittal parameters (PT, SS, PI-LL, and LL) and the development of ASD. Moreover, Saitoh et al. found that preoperative LL was significantly lower and PT was significantly higher in the postoperative ASD group compared to controls. ...

... De-repression of paternal Cdkn1c-Fluc-lacZ initiated early in gestation can continue beyond birth and long after LPD exposure, whilst gestational sensitivity to LPD is ameliorated by supplementation of maternal LPD with folate, which effectively restores correct DNA methylation across the sDMR 28 . Independent studies by others have also shown that folate depletion in pregnancy impacts brain development in adults 27,31,34 and that Cdkn1c upregulation can alter the proliferation and differentiation of developing dopaminergic neurons within the midbrain 20,27,29 . We therefore examined the brains and the behaviours of juvenile and adult offspring that had experienced gestational LPD exposure. ...

... Supplementation of maternal LPD with folate as a source of methyl-donors, corrects methylation across the sDMR and substantially reduces Cdkn1c misexpression in the resulting offspring 28 . These results show some similarity to prior genetic experiments where relatively mild over-expression of Cdkn1c was shown to be sufficient to provoke increased numbers of TH-positive cells in the periventricular hypothalamus and VTA, and a range of behavioural abnormalities that included altered reward-related and social dominance behaviours [20][21][22]29 . Maternally inherited loss of function of Cdkn1c has also been reported to result in reduced numbers of Nurr1-positive and TH-positive cells in the ventral midbrain at E18.5 54 . ...

... The association between parameters of visual gamma and the neural E/I balance, however, is not straightforward. Despite an initial encouraging report 17 , larger follow-up studies failed to find associations between amplitude or frequency of the visual gamma response (GR) induced by static gratings and concentration of GABA and glutamate assessed in the visual cortex using magnetic resonance spectroscopy 18,19 . Moreover, a study on patients with photosensitive epilepsy-a disorder characterized by extremely high excitability of the visual OPEN ...