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Early motor and sensory developmental delays precede Autism Spectrum Disorder (ASD) diagnosis and may serve as early indicators of ASD. The literature on sensorimotor development in animal models is sparse, male centered, and has mixed findings. We characterized early development in a prenatal valproic acid (VPA) model of ASD and found sex-specific developmental delays in VPA rats. We created a developmental composite score combining 15 test readouts, yielding a reliable gestalt measure spanning physical, sensory, and motor development, that effectively discriminated between VPA and control groups. Considering the heterogeneity in ASD phenotype, the developmental composite offers a robust metric that can enable comparison across different animal models of ASD and can serve as an outcome measure for early intervention studies.

Lead (Pb2+), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. However, the molecular processes affected by Pb2+ causing structural and functional anomalies are still unclear. To explore this, we employed behavioral and proteomic approaches using rat pups exposed to lead acetate through maternal lactation from postnatal day 0 (P0) until weaning. Behavioral results from three-month-old rats clearly emphasized the early life Pb2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb2+ induced cognitive abnormalities, we identified 45 key SUMO target proteins. The significant downregulation of SUMO target proteins such as metabotropic glutamate receptor 3 (GRM3), glutamate receptor isoforms 2 and 3 (GRIA 2 and GRIA3) and flotilin-1 (FLOT1) indicates SUMOylation at the synapses could contribute to and drive Pb2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition. Data availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212&#34.

The cellular and molecular effects of stress on the amygdala are strikingly different compared with those in the hippocampus. Previous findings on stress-induced plasticity were based primarily on postmortem analysis within individual areas. However, little is known about how stress affects dynamic changes and interactions in neuronal activity between the two areas. Hence, we simultaneously monitored in vivo activity of neuronal populations located in hippocampal areas CA1 and CA3 and the lateral amygdala (LA) in rats during and after chronic immobilization stress. The amplitude of auditory-evoked potentials (AEPs) in the hippocampus increased transiently only after a single 2 h stress but not when it was repeated for 10 d. In contrast, both acute and chronic stress caused a persistent increase in AEPs in the LA. Chronic stress also elicited a sustained increase in the LA but a decrease in the hippocampus in the evoked power of gamma and beta frequencies. Moreover, beta and gamma synchrony was reduced between areas CA1 and CA3 but enhanced between the LA and hippocampus after chronic stress. Granger causality spectra revealed a strong directional influence from the LA to area CA1 that persisted throughout and even 10 d after chronic stress. However, directional coupling from hippocampal area CA3 to CA1 became weaker at the end of chronic stress. Thus, our findings suggest that the growing dominance of amygdalar activity over the hippocampus during and even after chronic stress may contribute to the enhanced emotional symptoms, alongside impaired cognitive function, seen in stress-related psychiatric disorders. [ABSTRACT FROM AUTHOR]

Mice are favourite subjects in molecular and genetic memory research and frequently studied with classical fear conditioning paradigms that use an auditory cue (conditioned stimulus, CS+) to predict an aversive, unconditioned stimulus (US). Yet the conditions that control fear memory specificity and generalisation and their behavioural expression in such conditioned mice have not been analysed systematically. In the current study we addressed these issues in the most widely used mouse strain of behavioural genetics, C57Bl/6. In keeping with findings in other species we demonstrate the dependence of fear memory generalisation on training intensity (i.e. both US intensity and the number of CS+ and US applied) after both excitatory (explicitly paired presentation of CS+ and US) and inhibitory training (explicitly unpaired presentation of CS+ and US). Furthermore, inhibitory overtraining was associated with changes of uncued anxiety-like behaviour in a light/dark exploration test, indicative of an emotional sensitisation reaction as consequence of a lack of US predictability. Together our results describe the qualitatively and quantitatively different increases of defensive behaviour in response to conditioned stimuli of different salience and identify training conditions that lead to fear memory generalisation and emotional sensitisation in C57Bl/6 inbred mice. [Copyright &y& Elsevier]