PREVENTION OF CA2+-MEDIATED ACTION-POTENTIALS IN GABAERGIC LOCAL CIRCUIT NEURONS OF RAT THALAMUS BY A TRANSIENT K+ CURRENT

1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue,with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na+-K+-mediated spikes: the T-type Ca2+ current (I-T) and an A-type K+ current (I-A). Taking into account the differences in membrane surface area, the average size of I-T was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of I-T and I-A, were largely overlapping (V-H= -81.1 vs. -82.8 m V), both currents activated at around -70 m V, and they rapidly increased in amplitude With further depolarization. In relay cells, the inactivation curve of I-T was negatively shifted along the voltage axis by about 20 m V compared with that of I-A (V-h = -86.1 vs. -69.2 m V), and the activation threshold for I-T (at -80 m V) was 20 m V more negative than that for I-A. In interneurones, the activation range of I-T was shifted to values more positive than that in relay cells (V-h = -54.9 vs. -64.5 m V), whereas the activation range of I-A (V-h = -25.2 vs. -14.5 m V). 5. Under whole-cell voltage-clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from -110 m V evoked inward currents resembling I-T in relay cells and small outward currents indicative of I-A in local circuit neurones. After blockade of I-A With 4-aminopyridine (4-AP), the same pulse protocol produced I-T in both types of neurones. Under current clamp, 4-AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones. In relay cells, 4-AP increased the amplitude and duration of the Ca2+ action potential. 6. It is concluded that the voltage-dependent properties of I-T and I-A are delicately balanced in the two types of LGN neurones; in relay cells, the balance is shifted towards I-T and production of a low-threshold Ca2+ action potential, and I-A contributes to shaping the form of the regenerative depolarization; in local circuit neurones, the properties of I-T and I-A are widely overlapping, resulting in a functional compensation in terms of net membrane current, such that a regenerative Ca2+ response is prevented.