Auditory processing in rodent models of autism: a systematic review

Abstract

Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population. A search was conducted in the PubMed and Web of Science databases to find primary research articles in mouse or rat models of autism which investigate central auditory processing. A total of 88 studies were included. These used non-invasive measures of auditory function, such as auditory brainstem response recordings, cortical event-related potentials, electroencephalography, and behavioural tests, which are translatable to human studies. They also included invasive measures, such as electrophysiology and histology, which shed insight on the origins of the phenotypes found in the non-invasive studies. The most consistent results across these studies were increased latency of the N1 peak of event-related potentials, decreased power and coherence of gamma activity in the auditory cortex, and increased auditory startle responses to high sound levels. Invasive studies indicated loss of subcortical inhibitory neurons, hyperactivity in the lateral superior olive and auditory thalamus, and reduced specificity of responses in the auditory cortex. This review compares the auditory phenotypes across rodent models and highlights those that mimic findings in human studies, providing a framework and avenues for future studies to inform understanding of the auditory system in autism.

Keywords: Auditory; Auditory brainstem recordings; Autism spectrum disorder; Cortical event-related potentials; Rodent models.

Fig. 1

Key structures in the auditory processing pathway in the human and mouse brain. Auditory information enters the central nervous system at the cochlear nuclei and is then processed at the level of the superior olivary complex, lateral lemniscus, inferior colliculus, auditory thalamus (medial geniculate nucleus and thalamic reticular nucleus), auditory cortex, and prefrontal cortex. Scale bars are approximate. Images generated with brainrender [18]

Fig. 2

A Search strategy for systematic review. Records were found from searches in two databases. After removing duplicated entries, 234 abstracts were screened for inclusion in the review. Of these, 88 were primary research articles investigating the structure and function of the auditory processing pathway in mouse or rat models of autism. B Publication year of the records which were included in the review. Almost all records were published in the last 10 years

Fig. 3

Measures of function in along the auditory pathway. A Example human auditory brainstem response (ABR) trace. The first peak represents activity in the auditory nerve, and the second correlates to the cochlear nucleus. Peak III represents the superior olivary complex, and peaks IV and V represent the lateral lemniscus and the inferior colliculus, respectively. B Example cortical auditory event-related potential (ERP) trace. The ERP is made up of 5 peaks, representing activation in different areas. P1 is produced by activity in the auditory thalamus (MGN) and the primary auditory cortex, N1 is produced by the auditory cortex. P2 is produced by the association cortex. N2 and P3 peaks (associated with the frontal cortex) are observed in humans, but less commonly in rodents. C Exemplar EEG frequency activity. Raw EEG traces (as may be recorded from the auditory or prefrontal cortices) are composite waves, from which activity in several frequency ranges can be extracted. The power in each of these frequency bands indicates the extent to which activity at that frequency contributes to the overall recorded activity

Fig. 4

The ascending auditory processing pathway with presumed changes in autism based on results from studies in rodent models. Excitatory (red) and inhibitory (blue) connections between structures along the pathway are illustrated along with the changes to these connections and the activity within areas in rodent models of autism. Connections are primarily ipsilateral unless otherwise stated. There is increased activity in structures such as the lateral superior olive (LSO), the medial geniculate nucleus of the thalamus (MGN), thalamic reticular nucleus (TRN), the auditory cortex (specifically in layers 2/3), and the prefrontal cortex. Activity is consistently decreased in the dorsal and ventral lateral lemniscus (DNLL and VNLL) and the anterior auditory field (AAF) of the rat auditory cortex. Activity in other areas is either unchanged or results are conflicted. The connection from the ventral cochlear nucleus (VCN) to the LSO is increased in strength, while the strength of the connection from the anterior VCN (AVCN) to the medial nucleus of the trapezoid body (MNTB) is decreased. Signals from the VCN take longer to reach the SPON and from the MGN take longer to reach the auditory cortex in rodent models of autism. The speed of other connections is either unchanged or disputed between studies. The strength of connections between contralateral auditory cortices and between the auditory and prefrontal cortex is decreased, as is the feedback connection from the prefrontal cortex to the TRN