Adaptive, behaviorally gated, persistent encoding of task-relevant auditory information in ferret frontal cortex

Abstract

Top-down signals from frontal cortex are thought to be important in cognitive control of sensory processing. To explore this interaction, we compared activity in ferret frontal cortex and primary auditory cortex (A1) during auditory and visual tasks requiring discrimination between classes of reference and target stimuli. Frontal cortex responses were behaviorally gated, selectively encoded the timing and invariant behavioral meaning of target stimuli, could be rapid in onset, and sometimes persisted for hours following behavior. These results are consistent with earlier findings in A1 that attention triggered rapid, selective, persistent, task-related changes in spectrotemporal receptive fields. Simultaneously recorded local field potentials revealed behaviorally gated changes in inter-areal coherence that were selectively modulated between frontal cortex and focal regions of A1 that were responsive to target sounds. These results suggest that A1 and frontal cortex dynamically establish a functional connection during auditory behavior that shapes the flow of sensory information and maintains a persistent trace of recent task-relevant stimulus features.

Figure 1

Sites of physiological recordings. (a) Lateral view of the ferret brain indicating location of auditory (AC) and frontal (FC) cortices. The AC is located on the anterior, middle and posterior ectosylvian gyri (AEG, MEG, PEG), with primary auditory cortex (A1) situated in posterior MEG. Ferret PFC includes orbital gyrus (OBG) and the rostral portion of anterior sigmoid gyrus (ASG). We recorded from dorsal OBG and/or rostral ASG (dark green), and simultaneously in A1 (dark red). The numbers (1-3) indicate rostrocaudal position of neuroanatomically confirmed recording sites in PFC, shown in two representative brains in b and corresponding coronal sections in c. (b) Dorsal view of brains of two experimental ferrets. FC recording areas are encircled (recordings were made bilaterally, but for simplicity, are shown only in the right hemisphere). Numbered lines indicate rostrocaudal position in PFC of coronal sections shown in c. Stars indicate recording sites marked by lesions and fluorescent dye. (c) Coronal Nissl-stained sections from three rostrocaudal levels of FC (as indicated in b) showing recording sites. (1): section through OBG. Arrowheads indicate entrance and endpoint of penetrations in dorsal OBG marked by lesions. (2): section at rostrocaudal level of the transition between OBG and rostral ASG. The arrowhead points to cortical depression caused by numerous electrode penetrations superficially marked by fluorescent dye (green beads) shown in lower inset. (3): section through rostral ASG. Arrowheads point to two recording sites labelled with fluorescent dye (green beads), shown in greater detail in upper inset.

Figure 2

Behavioral paradigm and examples of typical FC neuron responses. (a) Conditioned avoidance task structure. In each trial, the animal was presented with a random number (1-7) of reference sounds (gray), to be discriminated from a target sound (black) that differed along a feature dimension that defined the task. Animals licked water from a spout throughout the reference stimuli, and learned to refrain from licking upon hearing the target sound in order to avoid receiving a mild shock during the “shock window” 400-800 ms after target offset. All auditory stimuli were of equal duration (either 1 s or 1.5 s in a given behavioral block) and sound level (70 dB). In most tasks, reference sounds consisted of spectro-temporally modulated broadband noise. In detection tasks, the target stimulus could vary substantially. The animals were trained to respond to a range of acoustic targets such as a pure tone (fixed or variable frequency), tone-in-noise, or click-train. In the two-tone discrimination task, both reference and target stimuli were hybrid sounds, consisting of modulated noise stimuli with a tone attached at the end: the two end-tones for reference and target differed in frequency. In the visual task, reference stimuli consisted of a series of steady lights followed by a brighter, rapidly flashing target light. (b)Unit showing enhanced responses during a tone-detection task. The peri-stimulus time histogram (PSTH) response to the target tone (black) and the reference noise (gray) were aligned to the onset of 1-s long stimuli (indicated by gray bar at top; white bar indicates silent “reaction interval” period – extending from target offset to 400 ms post-offset; black bar indicates 400 ms shock window between 400-800 ms following target offset). No responses were observed during passive presentation of the acoustic stimuli prior to the task. During the task, only the target tone elicited strong responses that declined gradually after the end of the tone. Post-task, the response to the target persisted weakly. (c)PSTH response of a suppressed cell in a detection task sequence. Panels display responses of the same FC neuron before behavior, and during a series of detection tasks (for three types of target – tone, tone-in-noise and click train). Prior to behavior, activity was weakly suppressed by target sounds, perhaps because of persistent effects from prior behavioral sessions earlier in the same recording day. During the behavior, suppression was stronger and built up over time, becoming substantially stronger well past the offset of the target tone, through the 400 ms reaction window and into the 400 ms shock window.

Figure 3

FC population target responses during tone-detection behavior. (a) Three heat maps show population responses (n=208) to target sounds during presentation of tone-detection stimuli in pre-behavior passive condition (left panel), during active behavior (middle panel), and in post-behavior passive condition (right panel). Each horizontal line illustrates modulation in a single neuron for 400 ms before target onset, 1 sec during the stimulus and 800 ms after offset. Neurons were normalized to have the same peak modulation, grouped by sign (enhanced versus suppressed) and ordered by onset latency of modulation during behavior. Red indicates activity enhanced from baseline and blue indicates suppressed activity. After behavior, there were some faint, persistent post-behavioral passive effects (right panel). In contrast, the little modulation present in the left panel pre-behavioral passive heat map is likely due to the imprint of previous behavioral sessions on the same recording day. (b) Each panel displays the population average target and reference PSTH for neurons with enhanced target responses, during behavior in a. Stimulus and shock windows are labeled as in Figure 2. During behavior, population activity increased rapidly after the target onset (black line) and was sustained through the shock window before returning rapidly to baseline. Very little modulation to reference stimuli was observed (gray line). In addition to being weaker, persistent modulation after behavior returned to baseline soon after target offset. (c) Average target and reference modulation for target-suppressed cells in a. During behavior, response latency was slightly slower than for enhanced neurons, but otherwise showed similar persistence.

Figure 4

FC class-specific responses to task-relevant sounds. (a) A single unit's response to two randomly alternating target tones in a tone detection task, plotted as in Fig. 2. This cell responded equally well to either of the two target tones (550 or 2200 Hz) but not to any of the 30 different reference noise stimuli. (b) During two-tone discrimination the 550 Hz (low) tone became a reference sound, and the unit now stopped responding to this tone, while maintaining its response to the 2200 Hz (high) tone, which remained a target. (c) Each point indicates the response of a neuron (n=66/115 responsive neurons) to the same target tone during tone detection (vertical axis) and discrimination (horizontal axis). Responses to the target tone were strongly correlated between behavior conditions (r=0.51, p<0.001). The dashed ellipse indicates the first (major axis) and second (minor axis) principal components of the covariance matrix of target responses under the two task conditions. The regression line (black) has a slope of 0.9, indicating that response magnitude was similar in both conditions. (d) Responses of the same neurons to the tone whose task-related ‘stimulus class’ or ‘meaning’ switched from target during tone detection to reference during the two-tone discrimination task, plotted as in c. Responses were much weaker when the tone acted as a reference in the two-tone discrimination task, and the responses were not correlated between behavior conditions (r=0.16, p>0.2).

Figure 5

Persistence and extinction of FC responses following behavior. (a) Neuron showing persistent target modulation following tone detection behavior. Behavior condition (passive or active) and time relative to the beginning of behavior (hours:minutes) is indicated in the upper right of each panel, with PSTHs plotted as in Fig. 2. The target response post-behavior was more phasic than during behavior and faded within one hour after the task performance. (b) Neuron showing exceptionally persistent modulation, plotted as in a. Target responses persisted over two hours after the task was completed and returned rapidly to high levels during a second behavior session. (c) Average normalized response magnitude for the population of 208 behaviorally activated neurons, as a function of trial number since the beginning of each epoch (i.e., before (green), during (red), after (blue), and long after (black) behavior). The dashed blue line indicates responses of the subset of 99 “persistent” neurons that were significantly modulated after the end of the behavioral session. (d) Scatter plot comparing target modulation during behavior (horizontal axis) versus post-behavior for all neurons showing sensory modulation during behavior (n=208). Black dots indicate units for which target responses were either significantly weaker or not significantly modulated during passive listening (p<0.05, t-test, 144/208, 69%). Responses post-behavior (vertical axis) were similar to responses during behavior (horizontal axis), although weaker (r=0.55, p<0.001, slope=0.31).

Figure 6

Selective top-down modulation of LFP in A1 and FC. (a) Average event related potential (ERPs) in FC (n=362 sites) evoked by reference (left panel) and target stimuli (right panel) during pre-behavior passive presentation (gray line) of tone detection stimuli and during behavior (black line). Variance of responses is reported for passive (gray) and behavior (black) in the upper right corner of each panel. ERPs occurred for both references and targets during passive presentation, despite the absence of spiking responses. During behavior, the magnitude of ref-ERP was reduced, while the tar-ERP showed two peaks of stronger, early hyperpolarization (100-200 ms) and stronger, late depolarization (400-600 ms) and later hyperpolarization (> 600 ms). (b) Average coherence of LFP recorded simultaneously in A1 and FC during reference phase of tone detection behavior (left panel, n=339 A1-FC site pairs). During passive presentation of reference sounds (both pre-behavior, light gray curve, and post-behavior, dark gray curve), there was strong coherence in the alpha-beta frequency range (10-20 Hz). This coherence was greatly diminished during behavior (black). Average coherence measured during the first 10 trials of each condition (~40 reference stimuli) reveals that the passive post-behavior condition was only partially restored to the original pre-behavior baseline, reflecting the persistent change in coherence and the gradual return of intra-areal communications to the passive state. (c) In some recordings (n=102 site pairs), there were two successive tone detection behavioral blocks with different target frequencies. Data were divided into two groups, pairs where the target frequency was near the best frequency (BF) of the A1 site (“near,” left panel) or far from the BF (“far,” right panel). The behaviorally-induced decrease in 10-20 Hz modulation occurred for near A1 sites. The decrease in FC-A1 coherence was dramatically diminished for far A1 sites.

Figure 7

Bimodal and unimodal sensory responses in FC. (a) Example of single unit responses to successive auditory and visual tasks, plotted as in Fig. 2. This cell showed modulation during behavior only to the auditory target. (b) A second neuron showed target modulation by both the visual and the auditory stimuli. This cell also responded persistently after behavior, particularly to the visual target. (c) Scatter plot of auditory (horizontal axis) and visual (vertical axis) target responses shows that cells responded similarly if they were bimodal (i.e., responded to both auditory and visual stimuli, n=93, r=0.30, p<0.01).