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Journal of Neuroscience, Vol 12, 3804-3817, Copyright © 1992 by Society for Neuroscience
A novel T-type current underlies prolonged Ca(2+)-dependent burst firing in GABAergic neurons of rat thalamic reticular nucleus
JR Huguenard and DA Prince
Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305.
The inhibitory GABAergic projection of thalamic nucleus reticularis (nRt)
neurons onto thalamocortical relay cells (TCs) is important in generating
the normal thalamocortical rhythmicity of slow wave sleep, and may be a key
element in the production of abnormal rhythms associated with absence
epilepsy. Both TCs and nRt cells can generate prominent Ca(2+)-dependent
low-threshold spikes, which evoke bursts of Na(+)-dependent fast spikes,
and are influential in rhythm generation. Substantial differences in the
pattern of burst firing in TCs versus nRt neurons led us to hypothesize
that there are distinct forms of transient Ca2+ current (I(T)) underlying
burst discharges in these two cell types. Using whole-cell voltage-clamp
recordings, we analyzed I(T) in acutely isolated TCs and nRt neurons and
found three key differences in biophysical properties. (1) The transient
Ca2+ current in nRt neurons inactivated much more slowly than I(T) in TCs.
This slow current is thus termed I(Ts). (2) The rate of inactivation for
I(Ts) was nearly voltage independent. (3) Whole-cell I(Ts) amplitude was
increased when Ba2+ was substituted for Ca2+ as the charge carrier. In
addition, activation kinetics were slower for I(Ts) and the activation
range was depolarized compared to that for I(T). Other properties of I(Ts)
and I(T) were similar, including steady-state inactivation and
sensitivities to blockade by divalent cations, amiloride, and antiepileptic
drugs. Our findings demonstrate that subtypes of transient Ca2+ current are
present in two different classes of thalamic neurons. The properties of
I(Ts) lead to generation of long-duration calcium-dependent spike bursts in
nRt cells. The resultant prolonged periods of GABA release onto TCs would
play a critical role in maintaining rhythmicity by inducing TC
hyperpolarization and promoting generation of low-threshold calcium spikes
within relay nuclei.
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