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.