Encoding by synchronization in the primate striatum

Abstract

Information is encoded in the nervous system through the discharge and synchronization of single neurons. The striatum, the input stage of the basal ganglia, is divided into three territories: the putamen, the caudate, and the ventral striatum, all of which converge onto the same motor pathway. This parallel organization suggests that there are multiple and competing systems in the basal ganglia network controlling behavior. To explore which mechanism(s) enables the different striatal domains to encode behavioral events and to control behavior, we compared the neural activity of phasically active neurons [medium spiny neurons (MSNs), presumed projection neurons] and tonically active neurons (presumed cholinergic interneurons) across striatal territories from monkeys during the performance of a well practiced task. Although neurons in all striatal territories displayed similar spontaneous discharge properties and similar temporal modulations of their discharge rates to the behavioral events, their correlation structure was profoundly different. The distributions of signal and noise correlation of pairs of putamen MSNs were strongly shifted toward positive correlations and these two measures were correlated. In contrast, MSN pairs in the caudate and ventral striatum displayed symmetrical, near-zero signal and noise correlation distributions. Furthermore, only putamen MSN pairs displayed different noise correlation dynamics to rewarding versus neutral/aversive cues. Similarly, the noise correlation between tonically active neuron pairs was stronger in the putamen than in the caudate. We suggest that the level of synchronization of the neuronal activity and its temporal dynamics differentiate the striatal territories and may thus account for the different roles that striatal domains play in behavioral control.

Figure 1.

Behavior and recording during the classical conditioning task. a, Left, Classical conditioning paradigm. Visual cues were presented for 2 s and predicted the delivery of food (reward trials, upper row), air puff (aversive trials, third row), or only sound (neutral trials, second row). The trial outcome epoch was followed by a variable ITI of 5–6 s. Right, Normalized behavioral response (average ± SEM, solid line and shaded envelope, respectively). The monkeys' licking and blinking behavioral responses were normalized between 0 and 1. In each time bin (20 ms), the licking and/or blinking response (x) was transformed by (x − min)/(max − min), where min and max are the minimal and maximal values of the response over all time bins, respectively. Ordinate shows normalized licking response minus normalized blinking response; abscissa shows time. Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. Blue indicates reward trials; green, neutral trials; and red, aversive trials. b, Recording sites. Shown is a representative coronal section +3 mm from the anterior commissure (adapted from Martin and Bowden, 2000). Eight electrodes were advanced separately into one or two of the three subregions of the striatum. P, Putamen; C, caudate; V, VS. c, Example of six simultaneously recorded units from the putamen. Each row is for a single electrode. Left, A 4 s analog trace of extracellular recording filtered between 300 and 6000 Hz. Right, Examples of spike waveforms. The spike waveform plot includes 100 superimposed 4 ms waveforms selected randomly from the whole recording time of the cell. Black, MSNs; gray, TANs.

Figure 2.

MSNs in the different striatal subregions display similar spiking parameters. a, Distribution of average MSN spontaneous (ITI) firing rates by striatal subregions. Abscissa shows the firing rate in Hz. The firing rate was calculated for each unit as the total number of spikes divided by the duration of the full-time segment used for analysis. The firing rate is displayed in logarithmic scale for clarity due to the low firing rates and wide range (0.01–7.8 Hz) of MSN discharge rates. Ordinate shows the ratio of cells. First row are MSNs recorded in the putamen (n = 344); second row, MSNs recorded in the caudate (n = 265); and third row, MSNs recorded in the VS (n = 287). b, Distribution of the coefficient of variation (CV) of the interspike intervals of MSNs in the striatal subregions. Abscissa shows the CV; ordinate, the fraction of cells (same conventions as in a). c, Distribution of average MSN waveform length by striatal subregions. Abscissa shows the spike waveform length calculated as the duration from the first negative peak to the next positive peak of the extracellular recorded action potential; the ordinate shows the fraction of cells (same conventions as in a).

Figure 3.

MSN cell population average response. a, Average MSN cell population response (±SEM) to behavioral events. Each row is the average response of MSNs recorded in a single striatal subregion. The PSTHs were calculated in 1 ms bins and smoothed with a Gaussian window with a SD of 20 ms. The baseline firing rate, calculated by averaging the firing rate in the last 0.5 s of the ITI, was subtracted from the smoothed PSTH. Abscissa shows the time in seconds. Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. The display is extended into the ITI to depict the return of the MSN discharge to baseline levels. Ordinate shows the firing rate in Hz. Blue indicates responses to all reward cues; green, responses to all neutral cues; and red, responses to all aversive cues. N indicates the number of neurons. b, Average MSN cell population response (±SEM) to behavioral cues alone. Cues were presented at time 0 (same conventions as in a). c, MSN cell population response to behavioral cues averaged over the absolute value of the PSTHs. The absolute PSTH was calculated for each neuron and then averaged over the entire population (same conventions as in b).

Figure 4.

MSNs in different striatal subregions display similar response profiles. a, MSN responses (±SEM) to the behavioral events divided into response clusters. Abscissa shows the time in seconds. Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. Ordinate shows the firing rate in Hz normalized by the ITI discharge rate. Blue RC, reward events; red AC, aversive events; green NC, neutral events. Rows are the striatal subregions: first row is the putamen; second row, the caudate; and third row, the VS. Columns show the average (±SEM, solid line and envelope) response clusters. In each subplot, N indicates the number of MSNs averaged and the percentage of these units of all the units in that subregion. b, Distributions of average MSN spike counts to cue presentation (time 0–2 s only). Each black dot represents an individual MSN. Red dots indicate population means. p, Putamen; c, caudate; v, VS. Asterisk marks statistically significant difference (p < 0.05 by one-way ANOVA). c, Distributions of time of peak response for all MSNs (same conventions as in b).

Figure 5.

MSNs in the putamen, but not in the caudate or VS, display positive signal and noise correlations. a, Distributions of the signal (left) and noise (middle) correlations for putamen MSN pairs. Abscissa shows correlation coefficient values; ordinate, ratio of pairs. Inset shows the ratio of pairs that had a significant positive (gray) or negative (black) correlation. Right: Correlation between the signal (abscissa) and noise (ordinate) correlation. N indicates the number of MSN pairs. Lower right, R² and a (slope) of the linear fit. b, Same as in a for the caudate MSN pairs. c, Same as in a for the VS MSN pairs.

Figure 6.

Putamen MSN pairs display different dynamics of noise correlation in the different behavioral events. a, Population JPSTH of putamen MSN pairs (n = 337). Left column shows reward trials; middle column, neutral trials; and right column, aversive trials. Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. The different JPSTHs have the same color scaling (color bar on the right) to enable comparison of the different behavioral events. b, Population JPSTH of caudate MSN pairs (n = 148). c, Population JPSTH of VS MSN pairs (n = 132). a, b, and c have the same color bar to enable comparison of striatal subregions.

Figure 7.

Dynamics of noise correlation of putamen MSN pairs do not reflect rate modulations. a, Common rate modulation: diagonal of the PSTH predictor (±SEM, shaded envelope) for putamen MSN pairs (n = 337). Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. Blue indicates reward cues; green, neutral cues; and red, aversive cues. b, Zero lag noise correlation: JPSTH diagonal (±SEM, shaded envelope) for putamen MSN pairs (n = 337; same conventions as in a).

Figure 8.

TANs in the different striatal subregions display similar spiking parameters. a, Distribution of average TAN spontaneous firing rates by striatal subregions. Abscissa shows firing rate in Hz; ordinate, ratio of cells. First row shows TANs recorded in the putamen; second row, caudate; and third row, VS (same conventions as in Figure 2a). b, Distribution of coefficient of variation (CV) of the interspike intervals of TANs in the three striatal subregions. Abscissa shows CV; ordinate, fraction of cells (same conventions as in a). c, Distribution of average TAN waveform length by striatal subregions. Abscissa shows spike waveform length calculated as the duration from the first negative peak to the next positive peak of the extracellular recorded action potential; ordinate, fraction of cells (same conventions as in a).

Figure 9.

TANs in different striatal subregions display similar response profiles. a, Average TAN population responses (±SEM) to behavioral events. Time 0 indicates the cue presentation followed by outcome delivery at time 2 s. Same conventions as in Figure 3a. b, Distributions of time of peak and minimum response and of average spike counts to cue presentation for all TANs. Each black/gray/blue dot represents an individual TAN. Red dots indicate population means. p, Putamen; c, caudate; v, VS. The distributions were not different across striatal subregions (one-way ANOVA). Black indicates time of minimum response; gray, time of peak response; and blue, average spike counts.

Figure 10.

Noise correlation between TAN pairs is stronger in the putamen than in the caudate. a, Distributions of signal (left) and noise (middle) correlations and the correlation between the two measures (right) for TAN pairs recorded in the putamen (first row, n = 72) and caudate (second row, n = 38). Same conventions as in Figure 5. b, Population JPSTH of TAN pairs. First row shows the putamen; second row, caudate (same pair numbers as in a, same conventions as in Figure 6).