THE WINDOW COMPONENT OF THE LOW-THRESHOLD CA2+ CURRENT PRODUCES INPUTSIGNAL AMPLIFICATION AND BISTABILITY IN CAT AND RAT THALAMOCORTICAL NEURONS

1. The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat an d cat thalamocortical (TC) neurones maintained in slices and by comput er simulation with a biophysical model of these neurones. 2. In a narr ow membrane potential range centred around -60 mV, TC neurones challen ged with small (10-50 pA), short (50-200 ms) current steps produced a stereotyped, large amplitude hyperpolarization (> 20 mV) terminated by the burst firing of action potentials, leading to amplification of th e duration and amplitude of the input signal, that is hereafter referr ed to as input signal amplification. 3. In the same voltage range cent red around -60 mV, single evoked EPSPs and IPSPs also produced input s ignal amplification, indicating that this behaviour can be triggered b y physiologically relevant stimuli. In addition, a novel, intrinsic, l ow frequency oscillation, characterized by a peculiar voltage dependen ce of its frequency and by the presence of plateau potentials on the f alling phase of low threshold Ca2+ potentials, was recorded. 4. Blocka de of pure Na+ and K+ currents by tetrodotoxin (1 uM) and Ba2+ (0.1-2 0 mM), respectively, did not affect input signal amplification, neithe r did the presence of excitatory or inhibitory amino acid receptor ant agonists in the perfusion medium. 5. A decrease in [Ca2(+)](o) (from 2 to 1 mM) and an increase in [Mg2+](o) (from 2 to 10 mM), or the addit ion of Ni2+ (2-3 mM), abolished input signal amplification, while an i ncrease in [Ca2+](o) (from 2 to 8 mM) generated this behaviour in neur ones where it was absent in control conditions. These results indicate the involvement of the low threshold Ca2+ current (I-T) in input sign al amplification, since the other Ca2+ currents of TC neurones are act ivated at potentials more positive than -40 mV. 6. Blockade of the slo w inward mixed cationic current (I-h) by 4-(N-ethyl-N-phenylamino)-1,2 dimethyl -6-(methylamino)-pyrimidinium chloride (ZD 7288) (100-300 mu M) did not affect the expression of the large amplitude hyperpolariza tion, but abolished the subsequent repolarization to the original memb rane potential. In this condition, therefore, input signal amplificati on was replaced by bistable membrane behaviour, where two stable membr ane potentials separated by 15-30 mV could be switched between by smal l current steps. 7. Computer simulation with a model of a TC neurone, which contained only I-T, I-h, K+ leak current (I-Leak) and those curr ents responsible for action potentials, accurately reproduced the qual itative and quantitative properties of input signal amplification, bis tability and low frequency oscillation, and indicated that these pheno mena will occur at some value of the injected DC if, and only if, the 'window' component of I-T (I-T,I-Window) and the leak conductance (g(L eak)) satisfy the relation (dI(T. Window)/dV)(max)) g(Leak). 8. The ph ysiological implications of these findings for the electroresponsivene ss of TC neurones are discussed, and, as I-T is widely expressed in th e central nervous system, we suggest that 'window' I-T will markedly a ffect the integrative properties of many neurones.