Learning produces differential tone responses

Adult males associate a 12-kHz tone with shock while a 2-kHz tone is unpaired. Greater later freezing to the former provides a learned frequency-cue distinction. Frequencies and prior meanings differ.

Testing uses settings distinct from training, with the two tones presented in different contexts. Freezing means immobility apart from breathing and describes learned defensive responses. The task compares behavioral differentiation of experienced cues.

After the task, most CPu-projecting AAF cells carry c-Fos. Forward labeling identifies many GABA-associated striatal recipients, motivating tests of their contribution.

Original figure 1AAF projections and striatal-recipient labeling

Lower recipient activity makes responses more similar

After learning, inhibition of AAF-recipient striatal GABA cells leaves tone-freezing differences nonsignificant, whereas controls retain a difference. The manipulation concerns retrieval-test expression of learned cue discrimination.

Different tone orders yield similar inhibition outcomes, relating responses to cue identity and experience rather than presentation order alone.

Original figure 2Responses after recipient inhibition

D1 and D2 populations differ

D1- and D2-receptor medium spiny neurons are principal striatal GABA populations. Inhibiting AAF-recipient D1 cells removes significant tone differentiation, while D2 inhibition preserves it.

The same auditory source engages recipient classes with distinct task contributions. D1-cell function extends into learned auditory-cue behavior, guiding downstream tracing.

Original figure 3Behavior after D1-recipient inhibition

Photoinhibition also alters differential responses

Test-time photoinhibition of D1 recipients also weakens differential freezing, while unilluminated conditions retain differentiation. Brief optical and chemogenetic results align.

These findings concern expression after learning cue meanings. Striatal recipients lie between auditory input and behavior, with their state influencing differential responses.

Original figure 5D1-recipient photoinhibition outcomes

Auditory input joins striatal–nigral output

D1-related terminals reach SNr, and retrograde tracing labels CPu. Combining AAF forward labeling with SNr GABA-associated monosynaptic tracing yields colabeled CPu cells, joining both ends anatomically.

SNr is a basal-ganglia output node. Researchers next select CPu D1 cells associated with both input and output to test their behavioral contribution.

Original figure 9Input/output-associated CPu colabeling

Inhibition and removal alter cue responses

Chemogenetic inhibition of the associated CPu D1 population makes freezing differences nonsignificant. Apoptotic removal yields a similar pattern, aligning reversible and cell-removal evidence.

Open-field distance and speed do not significantly change after ablation. Comparable locomotion accompanies altered differential tone responses, supporting a task-related contribution.

Original figure 8Population ablation and locomotor controls

The threat-predictive tone has clearer responses

SNr calcium responses to 12 kHz exceed fluorescence controls, while the 2-kHz comparison is nonsignificant, revealing distinct responses to learned cues.

The male-mouse study links differential tone responses with auditory cortex, striatal D1 cells and nigral-associated output, revealing cellular contributions to expressing distinct defensive responses after learning.

Original figure 10SNr calcium to the two tones