[Abstract Title]. - Society for Neuroscience

Authors: *D. BARRAZA 1 , C. J. WILSON 2 ;
2 Biol., 1 UTSA, San Antonio, TX
Abstract: Neurons of the subthalamic nucleus (STN) fire rhythmically in slices, even when
disconnected from synaptic input. When driven with short (1 s) depolarizing steps, they exhibit
reverse spike frequency adaptation and can fire at very high rates (up to 500 Hz). However, using
the perforated patch method to study longer current pulses, a slowly developing spike frequency
adaptation is apparent. Cells were driven by 2.5 minute current steps of various amplitudes. After
the initial rate increase during the first 50-200 ms after the onset of current injection, firing rate
gradually decreased over the next several seconds and stabilized at 18-63% of the maximal firing
rate. The adaptation could be described using two exponentials, a fast one with a time constant of
about 1.4 s and a longer one with a time constant averaging 23.0 s. Following current offset the
spontaneous firing was abolished for several seconds, followed by a gradual recovery of firing
rate with a time constant averaging 35.4 s. During adaptation, the variability of instantaneous
firing rate was greatly increased. Variability was measured as a deviation from the mean firing
rate during adaptation, and increased in parallel with adaptation and decreased during recovery.
Thus the influence of adaptation on variability was independent of rate, but depended upon
adaptation. Driving STN neurons with high frequency depolarizing voltage pulses in whole cell
voltage clamp recordings resulted in the accumulation of a slow apparent outward current that
outlasted the stimulus, and decayed with a time constant of about 1 second. We considered this
current a candidate for the mechanism responsible for spike frequency adaptation. The slow
outward current was reduced to zero below -70 mV, but never reversed, and increased in
amplitude rapidly at voltages above -55 mV. Using a voltage ramp from -70 to -30 mV, we
looked for changes in conductance that could be responsible for the outward current. We noted
that there was a reduction in the negative conductance region of the steady state I/V curve during
the period associated with the outward current, but no change in conductance at voltages outside
that range. The negative conductance region is caused by activation of a persistent sodium
conductance, as indicated by its sensitivity to TTX. Thus, the apparent outward current that
follows high frequency driven firing is actually a reduction in the voltage-dependent persistent
Na+ current that is known to be responsible for spontaneous firing. The slowly developing and
long-lasting inactivation of persistent Na+ currents can account for all the properties of the slow
spike frequency adaptation of STN neurons.
Disclosures: D. Barraza , None; C.J. Wilson, None.
Poster
240. Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs
and Activity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 240.18/E40