Henrik Jahnsen

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 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 effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.