The 'window' component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neurones

Stephen R. Williams, Tibor I. Tóth, Jonathan P. Turner, Stuart W. Hughes, Vincenzo Crunelli

    Research output: Contribution to journalArticlepeer-review


    1. The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat and cat thalamocortical (TC) neurones maintained in slices and by computer simulation with a biophysical model of these neurones. 2. In a narrow membrane potential range centred around -60 mV, TC neurones challenged 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 the duration and amplitude of the input signal, that is hereafter referred to as input signal amplification. 3. In the same voltage range centred around -60 mV, single evoked EPSPs and IPSPs also produced input signal amplification, indicating that this behaviour can be triggered by physiologically relevant stimuli. In addition, a novel, intrinsic, low frequency oscillation, characterized by a peculiar voltage dependence of its frequency and by the presence of plateau potentials on the falling phase of low threshold Ca2+ potentials, was recorded. 4. Blockade of pure Na+ and K+ currents by tetrodotoxin (1 μM) and Ba2+ (0.1-2.0 mM), respectively did not affect input signal amplification, neither did the presence of excitatory or inhibitory amino acid receptor antagonists 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 addition of Ni2+ (2-3 mM), abolished input signal amplification, while an increase in [Ca2+](O) (from 2 to 8 mM) generated this behaviour in neurones where it was absent in control conditions. These results indicate the involvement of the low threshold Ca2+ current (I(T)) in input signal amplification, since the other Ca2+ currents of TC neurones are activated at potentials more positive than -40 mV. 6. Blockade of the slow inward mixed cationic current (I(h)) by 4-(N-ethyl-N-phenylamino)-l,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD 7288) (100-300 μM) did not affect the expression of the large amplitude hyperpolarization, but abolished the subsequent repolarization to the original membrane potential. In this condition, therefore, input signal amplification was replaced by bistable membrane behaviour, where two stable membrane potentials separated by 15-30 mV could be switched between by small 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 currents responsible for action potentials, accurately reproduced the qualitative and quantitative properties of input signal amplification, bistability and low frequency oscillation, and indicated that these phenomena will occur at some value of the injected DC if, and only if, the 'window' component of I(T) (I(T,Window)) and the leak conductance (g(Leak)) satisfy the relation (dI(T,Window)/dV)(max) > g(Leak). 8. The physiological implications of these findings for the electroresponsiveness of TC neurones are discussed, and, as I(T) is widely expressed in the central nervous system, me suggest that 'window' I(T) will markedly affect the integrative properties of many neurones.
    Original languageEnglish
    Pages (from-to)689-705
    Number of pages16
    JournalJournal of Physiology
    Issue number3
    Publication statusPublished - 15 Dec 1997


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