Cellular mechanisms underlying pacemaking, variability and heterogeneity in the globus pallidus
Neurons in the external segment of the globus pallidus (GPe) fire in an autonomous fashion in vitro, and this persistent, self-generated, firing appears to influence the activity of GPe neurons in vivo. Therefore, understanding how the output of GPe neurons relates to its inputs will require not only a characterization of its synaptic inputs, but also their autonomous firing patterns and intrinsic membrane conductances, as they are inexorably linked. Electrophysiological recordings, pharmacology and computer modeling were used to characterize the ionic basis of two important aspects of autonomous firing: spike-to-spike variability (jitter) and heterogeneity, which are both likely to influence the network activity of GPe neurons. Because synaptic inputs are not needed to generate action potentials, it is possible that GPe neurons encode information in the relative timing of their action potentials, instead of the presence or absence of one. However, jitter poses a problem for a timing-based neural code by placing a limit on its fidelity. A combination of K+ channels interact with each other to determine how much jitter there will be in the firing pattern. The firing rates of GPe neurons spans a wide-range (1--70 Hz). This rate heterogeneity will influence the ability of GPe neurons to respond similarly to common inputs, and therefore the ability of the network to fire in a synchronized or desynchronized manner. In contrast to jitter, heterogeneity is controlled by slow fluctuations in inward currents, particularly those contributed by HCN channels. Thus, distinct ion channels control key features of autonomous firing in GPe neurons, which may allow GPe neurons to regulate each aspect of their firing independently to suit the needs of the network.