A systematic exploration of local network state space in neocortical mouse brain slices.

The ex vivo cortical slice is an extremely versatile preparation, but its utility ultimately depends on understanding its limitations and functional constraints. A question for experimentalists new to the field of cortical slice electrophysiology might be - what are the different network dynamical states available to a cortical slice as a function of excitatory drive? The purpose of this study is to provide a coherent answer to this question, within the context of extracellularly recorded population field potentials. Cortical slices (400 µm) were prepared from adult male or female C57 mice. Evoked responses were recorded within cortical layer III/IV using extracellularly positioned metal electrodes. In the first part of the study, slice excitatory drive was increased by reducing the concentration of magnesium ions in the artificial cerebrospinal fluid - and the evoked responses categorized during the transition. In the second part, each of the identified functional states were explored in greater detail with tissue perfusion conditions and excitatory drive optimised for the requisite response state. As expected, rodent cortical slices did not generate spontaneous, persistent EEG-like field potential activity. However, distinct response states (spontaneous and evoked) characterized by intermittent population bursts could be differentiated as a function of excitatory drive. Each state reflected different modes of neocortical activation: "monosynaptic" responses were brief, non-propagating activations, reflecting an inhibited cortex with sensory processing blocked; polysynaptic and epileptiform activity propagated intra-cortically, the latter reflecting a hyperactivated, hypersynchronous "seizing" cortex. Polysynaptic activity most closely resembled sensory "up states" associated with intracortical sensory processing. Understanding the functional distinction between the different cortical slice response states is the starting point for designing experiments that maximise the utility of this ex vivo model. The results and descriptions in this study should help slice experimentalists less experienced in the nuances of cortical slice neurophysiology to make informed choices about how to tailor the parameters of the model to suit the specific aims of their research.