Homeostatic control of intrinsic excitability of hippocampal neurons
A recent paper published in The Journal of Physiology uses Scientifica's PatchStar micromanipulator in an electrophysiological study that models the homeostatic regulation of intrinsic excitability (HRIE). The impressive stability of the PatchStar (drifting <1 μm in 2 hours) enabled accurate recordings to be taken over extended periods from the cultured hippocampal neurons.
The intrinsic electrical properties of a neuron in the central nervous system (CNS) is crucial to its functionality within a network of cells. Changes to a cell's physiological environment will have considerable impact on its excitability. It is therefore necessary for cells to have a method of coping with perturbations that occur through out its life. The hypothesized, and increasingly accepted, mechanism for regulation is homeostasis.
Researchers at the University of Edinburgh have proposed a simple model system in which they studied the responses of hippocampal neurons response to sustained depolarisation. They exposed cultures of primary hippocampal pyramidal neurons to increased levels of potassium chloride (KCl) to explore the dynamics and mechanisms of response over varying time scales, ranging from hours to weeks. O'Leary et al made whole-cell recordings from neurons that were either left in a 'control' extracellular solution or ones which contained elevated levels of KCl. They recorded the changes these treatments made to the intrinstic properties of the neurons and whether such changes were reversible and depended on calcium channel activity.
They observed that neurons exposed to elevated concentrations of extracellular KCl had lower input resistances and resting potentials and needed more current to be injected to evoke action potentials. This can be illustrated by a right-ward shift in the FI curve (spike rate vs current injected) of the cell. They found this shift to be dependent on the amount KCl concentrations were elevated by and importantly showed the changes were reversible indicating the existence of a very dynamic response to electrochemical changes. They also found that L-type calcium channel blocker nifedipine almost entirely blocked the shift in excitability.
Understanding a cell's physiological response to change is not only fascinating but is crucial for developing treatments for pathological conditions where the underlying problem may be a breakdown in a cell's homeostatic control. The simple model described in the paper published by O'Leary et al is very repeatable and easy to manipulate, allowing many possibilities for development in the future.
The Journal of Physiology 588.1 (2010) pp 157-170
Homeostasis of intrinsic excitability in hippocampal neurons: dynamics and mechanism of the response of chronic depolarization
Timothy O'Leary, Mark C. W. van Rossum and David J. A. Wyllie
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