1. Introduction
In patients, a clinical diagnosis of ASD is often based on highly penetrant phenotypes related to impairments in social communication and repetitive behaviors \cite{RN4,RN1,RN5,RN3}. However, there are often comorbid deficits present in the realm of cognition and memory, including impairments related to the core functions of the hippocampus: episodic memory, social interactions and networks, and cognitive mapping \cite{RN6}. As a result, there has been extensive work on the impact of mutations in ASD risk genes on hippocampal structure and function in rodents, spanning many distinct models and conducted on many different levels of analysis, from synapses up through circuits and behavior (for previous reviews see \cite{RN10,RN9,RN8,RN7}). Here we attempt to comprehensively examine these current data through the lens of animal models of ASD shown to lead to changes in neuronal excitability and synaptic function and their relationship to shifts in excitatory/inhibitory (E/I) balance on the circuit level, mediated through both neuronal and glia phenotypes. We believe that the commonalities in these findings can be a key reference point in guiding future work, both for the understanding and the treatment of the cognitive and social phenotypes present in ASD.
The hippocampus (Figure 1A), sitting in the temporal lobe, is required for the formation, storage and recall of the episodic memories of our daily lives \cite{RN11}. However, it also plays a larger role in mapping cognitive relationships across many domains, including spatial \cite{RN13,RN12}, value based \cite{RN14,RN16,RN15} and social networks \cite{RN17,RN18}. While many disorders, both neurodevelopmental and neurodegenerative, compromise hippocampal function, it has increasingly been one focus of research into autism spectrum disorder (ASD) in humans \cite{RN20,RN19,RN21,RN8} While there is broad consensus among both clinical and animal models of ASD that a shift in E/I balance in the hippocampus contributes to aspects of the disorder, the heterogenous changes which fall within the broad scope of this balance make it a challenge to understand \cite{RN22}. Further, the dynamic nature of E/I changes across both short and long timescales, as well as the dynamic physiology of the hippocampus itself, have made a mechanistic understanding of how these imbalances are manifest elusive. However, over 50 years of research on the physiology and function of the rodent hippocampus \cite{RN23}, both in vitro and in vivo, position it as an ideal model system to probe how changes in E/I balance result in dynamic changes in information representation and circuit dynamics during behavior.
In this review we will highlight a subset of model mice that have been characterized on the level of both the neuronal and glial contributions to synaptic function (Figure 1B), as well as on the circuit level, to connect the finding across these analyses. Specifically, we will focus on four broad families of models, those targeting neurexins/neuroligins, mutations in shank family proteins, loss of function of voltage-gated sodium channels and finally, monogenetic neurodevelopmental disorders, briefly introduced below, for which sufficient data exist for a comprehensive picture to emerge.