Author response: Computational models of O-LM cells are recruited by low or high theta frequency inputs depending on h-channel distributions

Neurons transmit information using electrical activity. Whereas electrical currents in wires consist of moving electrons, those in neurons are made up of charged particles called ions. These flow into and out of the cells through specialized channels in the outer membrane. Changes in ion channels can disrupt brain activity. However, unravelling the interactions between molecules that give rise to particular behaviours or diseases is challenging in living animals. Computer models can simplify this task, but only if the models are accurate copies of living systems. It is never possible to obtain a completely accurate model, so instead the goal is to make sure that any understanding derived from the models can guide new experiments, and that models are refined appropriately based on the results of these new experiments. Sekulić and Skinner used computer modelling to explore how ion channels affect the properties of a type of neuron called the oriens lacunosum/moleculare (O-LM) cell. These are found in a region of the brain called the hippocampus, which is involved in learning and memory. When animals explore their environment, the O-LM cells fire in synchrony with other cells in the hippocampus. Hippocampal cell populations typically fire either between 4 and 7 times per second, known as low theta, or 7 to 12 times per second, called high theta. Low theta firing supports the processing of emotions, whereas high theta helps animals form a mental map of their surroundings. Sekulić and Skinner wanted to know how the distribution of ion channels in O-LM cells – particularly a subtype called h-channels – affects whether the cells take part in theta firing. The task was made possible by the availability of a database of computer models of O-LM cells, each featuring a different distribution of ion channels. Sekulić and Skinner exposed each model to patterns of activity simulating those in the brain of an animal exploring its environment. The results revealed that specific combinations and distributions of ion channels predispose, or “tune”, O-LM cells to participate in either low or high theta, and thus emotional or spatial learning in the hippocampus. The next step is to test the predictions of the models experimentally. Studies should examine whether the distribution of ion channels in O-LM cells does indeed predispose them to fire at particular frequencies, as the models suggest. A further question is how targeting O-LM cells in freely moving animals would affect spatial and emotional memory.

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