Adaptation in the Visual Cortex: Influence of Membrane Trajectory and Neuronal Firing Pattern on Slow Afterpotentials

<div><p>The input/output relationship in primary visual cortex neurons is influenced by the history of the preceding activity. To understand the impact that membrane potential trajectory and firing pattern has on the activation of slow conductances in cortical neurons we compared the afterpotentials that followed responses to different stimuli evoking similar numbers of action potentials. In particular, we compared afterpotentials following the intracellular injection of either square or sinusoidal currents lasting 20 seconds. Both stimuli were intracellular surrogates of different neuronal responses to prolonged visual stimulation. Recordings from 99 neurons in slices of visual cortex revealed that for stimuli evoking an equivalent number of spikes, sinusoidal current injection activated a slow afterhyperpolarization of significantly larger amplitude (8.5±3.3 mV) and duration (33±17 s) than that evoked by a square pulse (6.4±3.7 mV, 28±17 s; p<0.05). Spike frequency adaptation had a faster time course and was larger during plateau (square pulse) than during intermittent (sinusoidal) depolarizations. Similar results were obtained in 17 neurons intracellularly recorded from the visual cortex <i>in vivo</i>. The differences in the afterpotentials evoked with both protocols were abolished by removing calcium from the extracellular medium or by application of the L-type calcium channel blocker nifedipine, suggesting that the activation of a calcium-dependent current is at the base of this afterpotential difference. These findings suggest that not only the spikes, but the membrane potential values and firing patterns evoked by a particular stimulation protocol determine the responses to any subsequent incoming input in a time window that spans for tens of seconds to even minutes.</p></div

Slow postpotential induced by two different patterns of stimulation in visual cortex neurons <i>in vitro</i>.

<p><b>A</b>. The postpotential evoked by the injection of a depolarizing square pulse of 20 sec of duration is compared against the one induced by injection sinusoidal current for 20 sec (right) in the same neuron recorded <i>in vitro</i>. The intensity (nA) of both stimuli was adjusted to evoke similar number of action potentials (245 spikes with the square pulse and 282 spikes with the sinusoid). In both cases, a slow afterhyperpolarization following the current injection was observed. A larger AHP (11 mV, 41 s duration) followed the injection of sinusoidal current than the square pulse (8 mV, 39 s duration). <b>B</b>. Expanded traces from A. <b>a, b, c, d</b>: Comparison of spike-frequency adaptation generated in response to intracellular injection of square pulse (<b>a, b</b>) and sinusoidal current (<b>c, d</b>). Notice that action potential discharge had adapted strongly at the end of the square pulse. <b>C</b>. Plot of the difference in the number of action potential evoked with both protocols for each of the neurons against the difference in afterpotential amplitude. Black point show the neurons with the difference of AP was ≤50.</p

Comparison of firing adaptation and afterpotential measured <i>in vivo</i> or <i>in vitro</i>.

<p><b>A.</b> AHPs recorded from a visual neuron <i>in vivo</i>: the square pulse evoked a smaller postpotential than sinusoidal current injection (4 mV and 49 s vs 6 mV and 54 s). <b>B</b>. Comparison between <i>in vivo</i> and <i>in vitro</i> conditions. Data are reported as mean ± SE. For sinusoidal current injection the values of adaptation index and postpotential was very similar in both conditions. <i>In vitro</i> conditions we observed a similar adaptation index from the same protocol but the postpotential was larger than <i>in vivo</i> condition.</p

Slow adaptation during action potential discharge.

<p>The time course and strength of the firing rate adaptation varies with the type of intracellular injection current (square pulse or sinusoidal current). <b>A</b>. Example of the plot of the rate of the decay (fit by a single exponential) during square pulse intracellular injection current. The firing rate has been normalized such that 100% corresponds to the firing rate at the beginning of each stimulus. <b>B</b>. Comparison of the time courses and amplitudes of adaptation during the injection of each stimulus in 10 cortical neurons. Note a larger adaptation evoked by square pulse than sinusoidal injection current. <b>C, D</b>. Distributions of adaptation index values calculated for 99 cortical neurons recorded <i>in vitro</i> for square pulses (40±20%, C) and for sinusoidal current (67±18%, D). Adaptation index is the percentage of spikes during the last 500 ms of the protocol with respect to the number of spikes during the first 500 ms.</p

The difference in afterpotentials generated by pulses and sinusoids is calcium dependent.

<p><b>A</b>. Intracellular injection of square pulse results in the generation of an ADP (<b>A</b>) and of sinusoidal current in a slow AHP (<b>B</b>). In low calcium (0.1 mM; B) the ADP disappeared and both protocols evoked similar AHPs (<b>A, B</b>). Left panels show the substraction of the afterpotentials. <b>C–D</b>. In a different neuron, local application of 500µM Nifedipine also abolished the differences in afterpotentials.</p

The Head-Mounted Display and Tracking.

<p>(A) Participants experienced the virtual environment through a stereo wide field-of-view Head Mounted Display. (B) Upper limbs were tracked by 12 Optitrack markers grouped in 4 trackable objects. The right and left forearms were tracked for all participants. For right handed people, the right hand and the left index finger were also tracked. For left handed people, the positions of the markers were swapped and thus the right finger and the left hand were tracked.</p

Path Model Estimates Corresponding to Figure 8.

<p>n = 40, Chi-squared goodness of fit  = 12.48, d.f.  = 9, P = 0.19.</p

Means and Standard Errors of the Angular drifts for the elongation conditions.

<p><i>AngleBefore</i> is the mean of 10 estimations of hand position at the start of the experiment. <i>AngleAfter</i> is the single estimation of hand position after the arm elongation period. <i>AngleAfter</i> is significantly greater than <i>AngleBefore</i> for <i>C2</i> (P = 0.04) and <i>C3</i> (P = 0.01) but not for <i>C4</i> (P = 0.17), Wilcoxon matched-pairs signed-rank tests.</p

The Experiment Conditions.

<p>n = 10 for each condition in a between-groups design. Congruent visuo-tactile correlation refers to the virtual arm being in contact with the Stimulus Box while the participant was touching it, and Incongruent refers to the virtual arm not reaching the Stimulus Box. In each condition there was visuo-motor synchrony between the real and virtual dominant arm.</p

The elongation of the virtual arm and the threat event to the virtual hand.

<p>(A) At the start of the experiment, both virtual arms were of the same size as the participant’s arms. In <i>C1</i> the virtual arm did not change length during the experiment. (B) The arm elongated to double the true length (<i>C2</i>) (C) The arm elongated to triple the true length (<i>C3</i>) (D) The arm elongated to four times the true length (<i>C4</i>). When the elongation was complete for the condition and after the last angular estimation was made, a virtual saw fell to cut the virtual arm. The participants had been instructed to stay motionless just before this. (E) The position of the virtual threat was also close to the physical body and the real hand in the no elongation condition <i>C1</i> (F) The threat was far from the real body and real hand in condition <i>C4</i>.</p