All thalamocortical neurones possess a T-type Ca2+ 'window' current that enables the expression of bistability-mediated activities.
1. The existence of a non-negligible steady-state ('window') component of the low threshold, T-type Ca2+current (IT) and an appropriately large ratio of IT to ILeak conductance (i.e. gT/gLeak) have been shown to underlie a novel form of intrinsic bistability that is present in about 15 % of thalamocortical (TC) neurones. 2. In the present experiments, the dynamic clamp technique was used to introduce into mammalian TC neurones in vitro either an artificial, i.e. computer-generated, IT in order to enhance endogenous IT, or an artificial inward ILeak to decrease endogenous ILeak. Using this method, we were able to investigate directly whether the majority of TC neurones appear non-bistable because their intrinsic ionic membrane properties are essentially different (i.e. presence of a negligible IT 'window' component), or simply because they possess a gT or gLeak conductance that is insufficiently large or small, respectively. 3. The validity of the dynamic clamp arrangement and the accuracy of artificial IT were confirmed by (i) recreating the low threshold calcium potential (LTCP) with artificial IT following its block by Ni2+ (0.5-1 mM), and (ii) blocking endogenous LTCPs with an artificial outward IT. 4. Augmentation of endogenous IT by an artificial analog or introduction of an artificial inward ILeak transformed all non-bistable TC neurones to bistable cells that expressed the full array of bistability-mediated behaviours, i.e. input signal amplification, slow oscillatory activity and membrane potential bistability. 5. These results demonstrate the existence of a non-negligible IT 'window' component in all TC neurones and suggest that rather than being a novel group of neurones, bistable cells are merely representative of an interesting region of dynamical modes in the (gT, gLeak) parameter space that may be expressed under certain physiological or pathological conditions by all TC neurones and other types of excitable cells that possess an IT 'window' component with similar biophysical properties.
Hughes
S W
SW
Physiology Unit, Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF1 3US, UK.
Cope
D W
DW
Tóth
T I
TI
Williams
S R
SR
Crunelli
V
V
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D020747:Calcium Channels, T-Type; D002415:Cats; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008322:Mammals; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D009991:Oscillometry; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000502:physiology*
D015220:Calcium Channels; D020747:Calcium Channels, T-Type