ABSTRACT

INTRODUCTION Brain responses involve coinciding contributions from multiple cell types sharing a highly organized microenvironment. In vitro cell culture techniques have the capacity to address mechanistic questions concerning cell-specifi c responses within the nervous system. The majority of these studies have relied heavily on dissociated primary cultures enriched in one or more distinct, neural cell types in isolation. While these types of preparations allow for an examination of specifi c mechanistic questions, they are signifi cantly hindered with regard to translation to the in vivo environment. Accurate modeling of neuronal toxicity, in particular, is highly dependent upon the cellular interactions available to the target cells in question. As such, the dynamic cell-cell interactions of the nervous system need to be considered to appropriately interpret and translate changes in neural activity and toxicity. Thus, many in vitro models have been designed with a goal towards maintaining endogenous functional interactions, including normal synaptic connections, between both neuronal and non-neuronal cell types. One approach to incorporate the three-dimensionality of in vivo systems into a culture model has been the use of organotypic slice cultures (OSCs). Such slice systems can maintain integrated components of in vivo neural architecture for extended periods of time in vitro.