RECOVERY OF CABLE PROPERTIES THROUGH ACTIVE AND PASSIVE MODELING OF SUBTHRESHOLD MEMBRANE RESPONSES FROM LATERODORSAL TEGMENTAL NEURONS

The laterodorsal tegmental nucleus (LDT) is located in the dorsolatera l pontine reticular formation. Cholinergic neurons in the LDT and the adjacent pedunculopontine tegmental nucleus (PPT) are hypothesized to play a critical role in the generation of the electroencephalographic- desynchronized states of wakefulness and rapid eye movement sleep. A q uantitative analysis of the cable properties of these cells was undert aken to provide a more detailed understanding of their integrative beh avior. The data used in this analysis were the morphologies of intrace llularly labeled guinea pig LDT neurons and the voltage responses of t hese cells to somatic current injection. Initial attempts to model the membrane behavior near resting potential and in the presence of tetro dotoxin (TTX, 1 mu M) as purely passive produced fits that did not cap ture many features of the experimental data. Moreover, the recovered v alues of membrane conductance or intracellular resistivity were often very far from those reported for other neurons, suggesting that a pass ive description of cell behavior near rest was not adequate. An active membrane model that included a subthreshold A-type K+ current and/or a hyperpolarization-activated cation current (H-current) then was used to model cell behavior. The voltage traces calculated using this mode l were better able to reproduce the experimental data, and the cable p arameters determined using this methodology were more consistent with those reported for other cells. Additionally, the use of the active mo del parameter extraction methodology eliminated a problem encountered with the passive model in which parameter sets with widely varying val ues, sometimes spanning an order of magnitude or more, would produce e ffectively indistinguishable fits to the data. The use of an active mo del to directly fit the experimentally measured voltage responses to b oth long and short current pulses is a novel approach that is of gener al utility.