Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

Table 1 Recommended assays for ASD-related changes in rodent models

Levels of analysis	Specific assays
Molecular assays	Focused biochemical and molecular assays directed at the targeted gene and pathway Unbiased proteomic and genome-wide gene expression analysis, with pathway and network analysis
Nervous system morphology assays	Gross pathology Analyses of neuronal fate and neuronal migration including tract-tracing Assessment of neuronal morphology, dendritic and spine integrity, and synaptic morphology
Electrophysiological assays	Use of evoked field potentials to assess basal synaptic properties, short-term plasticity, long-term plasticity, and analysis of seizure-like activity Patch-clamp recording for basic membrane properties, characterization of voltage- and ligand-gated ion channel currents, and assessment of spontaneous neurotransmission
Neurological assays	General observations, spontaneous and elicited behaviors Assessment of grip strength, sensitivity to pain, gait, accelerating rotarod, acoustic startle, and prepulse inhibition of acoustic startle Analysis of seizure susceptibility
Higher-order behavioral assays	Assessment of anxiety, open field/spontaneous locomotor behavior Analysis of social interaction/recognition, including ultrasonic vocalizations Assessment of learning and memory, including cued and contextual fear conditioning, Morris water maze, radial arm maze, and passive avoidance Recording of behavioral stereotypes

Based on a survey of findings, we conclude that five levels of analysis should be carried out on rodent ASD models. Four are derived from the unbiased enrichment analyses described in the main text and the fifth (molecular) is part of the standard and enhanced workup of novel model systems. In each of the five domains, specific assays are suggested, based on expert review of publications of at least 40 genes associated with electrophysiological, neurological, or higher behavioral features.

ISSN: 2040-2392