Faculty Bibliography

The ionic requirements for electro-responsiveness in thalamic neurones were studied using in vitro slice preparations of the guinea-pig diencephalon. Analysis of the current-voltage relationship in these neurones revealed delayed and anomalous rectification. Substitution of Na+ with choline in the bath or addition of tetrodotoxin (TTX) abolished the fast spikes and the plateau potentials, described in the accompanying paper. Ca2+ conductance blockage with Co2+, Cd2+ or Mn2+, or replacement of Ca2+ by Mg2+ abolished the low-threshold spikes (l.t.s.). Substitution with Ba2+ did not significantly increase the duration of the l.t.s., suggesting that under normal conditions the falling phase of this response is brought about by inactivation of the Ca2+ conductance. The after-hyperpolarization (a.h.p.) following fast spikes was markedly reduced in amplitude and duration by bath application of Cd2+, Co2+ or Mn2+, indicating that a large component of this response is generated by a Ca2+-dependent K+ conductance (gK[Ca]). Following hyperpolarizing current pulses, the membrane potential showed a delayed return to base line. This delay is produced by a transient K+ conductance as it can be modified by changing the drive force for K+. Presumptive intra-dendritic recording demonstrated high-threshold Ca2+ spikes (h.t.s.s.) which activate a gK[Ca]. Such h.t.s.s. were also seen at the somatic level when K+ conductance was blocked with 4-aminopyridine. It is proposed that the intrinsic biophysical properties of thalamic neurones allow them to serve as relay systems and as single cell oscillators at two distinct frequencies, 9-10 and 5-6 Hz. These frequencies coincide with the alpha and theta rhythms of the e.e.g. and, in the latter case, with the frequency of Parkinson's tremor.

The electroresponsive properties of guinea-pig thalamic neurones were studied using an in vitro slice preparation. A total of 650 cells were recorded intracellularly comprising all regions of the thalamus; of these 229 fulfilled our criterion for recording stability and were used as the data base for this report. The resting membrane potential for thirty-four representative neurones which were analysed in detail was -64 +/- 5 mV (mean +/- S.D.), input resistance 42 +/- 18 M omega, and action potential amplitude 80 +/- 7 mV. Intracellular staining with horseradish peroxidase and Lucifer Yellow revealed that the recorded cells had different morphology. In some their axonal trajectory characterized them as thalamo-cortical relay cells. Two main types of neuronal firing were observed. From a membrane potential negative to -60 mV, anti- or orthodromic and direct activation generated a single burst of spikes, consisting of a low-threshold spike (l.t.s.) of low amplitude and a set of fast superimposed spikes. Tonic repetitive firing was observed if the neurones were activated from a more positive membrane potential; this was a constant finding in all but two of the cells which fulfilled the stability criteria. The l.t.s. response was totally inactivated at membrane potentials positive to -55 mV. As the membrane was hyperpolarized from this level the amplitude of the l.t.s. increased and became fully developed at potentials negative to -70 mV. This increase is due to a de-inactivation of the ionic conductance generating this response. After activation the l.t.s. showed refractoriness for approximately 170 ms. Deinactivation of l.t.s. is a voltage- and time-dependent process; full de-inactivation after a step hyperpolarization to maximal l.t.s. amplitude (-75 to -80 mV) requires 150-180 ms. Membrane depolarization positive to -55 mV generated sudden sustained depolarizing 'plateau potentials', capable of supporting repetitive firing (each action potential being followed by a marked after-hyperpolarization, a.h.p.). The a.h.p. and the plateau potential controlled the voltage trajectory during the interspike interval and, with the fast spike, constitute a functional state where the thalamic neurone displayed oscillatory properties. Frequency-current (f-I) plots from different initial levels of membrane potential were obtained by the application of square current pulses of long duration (2s). From resting membrane potential and from hyperpolarized levels a rather stereotyped onset firing rate was observed due to the presence of the l.t.s.(ABSTRACT TRUNCATED AT 400 WORDS)

The electroresponsiveness of mammalian thalamic neurons was studied in a slice preparation of the guinea pig diencephalon. Although the morphology of the cells varied, their electroresponsive properties were the same. Stimulation of thalamic cells at a membrane potential more negative than--60 mV produced burst responses and stimulation of more depolarized levels produced tonic firing of fast spikes. The burst response is generated by an inactivating Ca++-conductance. It is seen as a slow Ca++-spike which in turn triggers fast Na+-spikes. The Ca++-conductance is deinactivated by hyperpolarization beyond--60 mV. The membranes of thalamic neurons contain a number of other conductances including a Ca++-dependent K+-conductance producing spike afterhyperpolarization and a non-inactivating Na+-conductance which plays an important role during tonic activity of the cells. The early part of a response to a long-lasting stimulus given at rest or at a hyperpolarized level is dominated by the burst and thus is is independent of the stimulus amplitude. During the late part of such a response the firing rate is highly dependent of the stimulus intensity. Current-frequency plots for the first inter-spike intervals after the burst during long stimuli are upward convex, but after 'steady-state' is reached the plots are almost linear.

The electrophysiological properties of neurons in the pars compacta of the substantia nigra have been examined in vitro in guinea pig mesencephalic slices. These cells display a set of voltage- and Ca2+-dependent ionic conductances which confer upon them rather unique electrophysiological characteristics. In particular, the results indicate the presence of two separate dendritic Ca2+ conductances. One is inactivated at rest membrane potential and is de-inactivated by membrane hyperpolarization. The second resembles that responsible for dendritic spikes in other neurons. These conductances fulfil most of the physiological and pharmacological requirements for the ionic mechanisms underlying Ca2+-dependent dendritic release.