The excitatory population responds to aversive events

Calcium signals rose in the labeled excitatory BLA population during tail suspension. Following chronic social defeat, responses to a social stimulus were greater than before stress. Activity-marker c-Fos findings also indicated altered BLA activity under stress.

Population calcium measurements give these changes a time course, with responses rising around particular stimuli. Individual cells and animals can still differ. Manipulating activity then allows the study to examine its links with context avoidance, social interaction and preference.

Original figure 1Calcium responses during tail suspension and social stimuli

Excitatory and inhibitory populations yield different outcomes

Recruiting the excitatory population reduced time spent on the stimulation-paired side, producing real-time place aversion, and increased the immobile fraction during tail suspension. These outcomes connect the population to aversive and immobility-related behavior.

Recruiting GABAergic cells decreased the immobile fraction during tail suspension without significantly changing occupancy of the stimulation-paired side. Increased local inhibition can affect one behavior without producing place preference. This distinction provides a starting point for examining stress-related outcomes.

Original figure 2Population differences in place behavior and tail suspension

The effects also depend on prior stress

Recruiting the excitatory population during subthreshold social defeat reduced social interaction and sucrose preference. Tail-suspension immobility and open-field center time did not significantly change, revealing different responses across measures.

After chronic social defeat, suppressing these cells over three consecutive days improved social interaction and sucrose preference and reduced tail-suspension immobility in supplementary experiments. Open-field center time did not significantly improve. The intervention affected selected outcomes across tasks.

Original figure 3Stress-related manipulation of the excitatory population

Changing inhibitory activity reshapes excitatory responses

Suppressing GABAergic cells increased calcium-event frequency in the labeled excitatory population. Conversely, recruiting GABA cells attenuated foot-shock-evoked excitatory-population calcium responses. These opposite manipulations connect local inhibition with excitatory responses.

GABA is a major inhibitory signal in the brain. Within a local network, inhibitory cells help shape neighboring cells’ responses. Examining them makes the regional description of amygdala hyperactivity more specific by identifying the responding population and cells able to constrain its responses.

This provides a cellular explanation for the behavioral findings: recruiting GABA cells can attenuate local excitatory-population responses to aversive stimulation. These are population calcium measurements; the most affected individual cells and distinct inhibitory subtypes remain to be examined.

Original figure 4GABA manipulations and excitatory-population calcium activity

Recruiting inhibition increases social approach

Suppressing GABA cells during subthreshold social defeat reduced social interaction and sucrose preference and increased tail-suspension immobility; supplementary experiments also found less open-field center time. Lower inhibitory activity promoted selected stress-related outcomes.

Recruiting GABA cells over three days after chronic defeat increased social interaction and sucrose preference in susceptible mice. Supplementary results showed less tail-suspension immobility and more open-field center time. This open-field outcome differs from direct suppression of the excitatory population, highlighting distinct profiles of local manipulations.

BLA receives inputs from multiple cortical areas and can integrate stress-related information. This study focuses on its internal excitatory–inhibitory interactions, identifying local cellular relationships as an entry point into behavioral regulation. The findings concern adult male mice; relevant inhibitory subtypes, effect duration and functions across sexes and human disease remain open.

Original figure 5Opposite behavioral effects of GABA manipulation