Primary Cortical Representation of Sounds by the Coordination of Action-Potential Timing

1. Primary Cortical Representation of Sounds by the Coordination of Action-Potential Timing R. Christopher deCharms & Michael M. Merzenich Take-home: “Population coding based on relative spike timing can systematically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.”

2. Rationale • Cortical population coding is still not understood. • Firing rates versus relative timing of firing • Changes in firing rates of most neurons do not reflect duration of a stimulus. • Sensorimotor neurons in frontal cortex change the relative timing of firing even when firing rate does not change. • Purpose: Investigate the role of relative action potential timing in population coding of stimuli in the primary auditory cortex.

3. Methods • 3 marmoset monkeys • Extracellular recordings from pairs of locations of neurons in the supragranular primary auditory cortex 75-1,000 µm apart • Computer sampling at 20 kHz and spike sorting • Thresholded signals gave 54 pairs of single units & 369 pairs of multiunit groups • Auditory stimuli produced by a DSP chip and presented binaurally • Statistical significance est. between cross-correlograms • Mean, s.e. & confidence limits derived from all trials (~100)

4. Question 1 • Do cortical neurons that fire at low rates provide information about stimuli?

5. Figure 1 Conclusion: “Cortical neurons can thus maintain signals about ongoing stimuli by temporally coordinating the few action potentials present even at low firing rates.” a–d: average cross-correlations between 2 locations (100 reps.) f & g: firing-rate response to a long-lasting stimulus similar to a brief 50 ms stimulus e: amplitude envelope; 70 dB at 4 kHz; pure-stimulus tone b & c: the change in coordinated rate was highly significant (P<1x10-5 for b, P>3x10-4 for c, permutation test) d: Control for remaining relative spike timing or short-term synaptic plasticity after the introduction of a stimulus: unchanged f & g: mean firing rates at the 2 locations

6. Question 2 • Is neuronal coordination effective at the level of individual pairs of neurons or at the population level?

7. Figure 2 a: single pair of neurons: increased cross-correlation during the stimulus, but variability too high b: single pair of neurons with a significant cross-correlation, but little or no change in tonic firing rate Conclusion: “Neuronal coordination is a population effect.” c: comparison of two groups of well-isolated units with similar effect to b, but more robust d: two thresholded multiunit groups; similar effect as in c e: single unit and the local field potential (adjacent electrode): increase in correlation with sound

8. Question 3 • Is neuronal coordination stimulus specific, and if so, how is this specificity represented on the cortex?

9. Figure 3 a-h: frequency tuning of spike time coordination between two groups of neurons 3e: coordination rate increases even when mean firing decreases Conclusion: “ Where firing rate and relative timing both change, the absolute number of coordinated events reflects both effects.” Coordinated rate of action potentials was increased significantly by a 4 kHz stimulus & significantly decreased by a 6.35 kHz stimulus

10. Figure 3 Conclusion: Topographic map of coordinated spike tuning reflects the map for traditional onset burst tuning. i-k: spatial locations on auditory cortex Red: increased coordinated rate Blue: decreased coordinated rate 4 kHz 70 dB 4 kHz 40 dB Center frequency of tonic phase coordinated spike rate tuning 2.52 kHz 40 dB

11. Question 4 • Does neuronal coordination mimic the duration of the stimulus at locations where the firing rate does not?

12. Figure 4 Conclusion: “…a target location which samples across a broad & non-homogeneous population of neurons that are firing on average near background rate can nonetheless extract the time course of an ongoing stimulus by using temporal coincidence information from that population.” e: mean plus s.e. of all the coordinated spike-rate time courses a: coordinated discharge rate at two locations b & c: no significant change in firing rate at the same two locations as in a (not even transients) f: average of all individual firing rates from same population as in e

13. Conclusions • At stimulus transients, population firing rate & coordinated firing rate both reflect the change in signal • Results reveal that relative spike timing of action potentials in the primary auditory cortex may be vital for signaling features of a stimulus once population firing rate has returned to baseline. • More basic than the concept of neuronal grouping • Evolving temporal pattern of activity