Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior

Abstract

The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here we leverage 2-photon calcium imaging combined with single cell holographic photostimulation through an endoscopic lens implanted in the deep brain to demonstrate a direct causal role for discrete ensembles of BLA neurons in the control of oppositely valenced behavior. We report that targeted photostimulation of individual groups of appetitive or aversive BLA neurons shifts behavioral responses toward those behaviors which recruited a specific consumption or avoidance ensemble. Here we identify that neuronal encoding of valence in the BLA is graded and relies on the relative proportion of individual BLA neurons recruited during a stable appetitive or aversive ensemble.

Distinct ventral tegmental area neuronal ensembles are indispensable for reward-driven approach and stress-driven avoidance behaviors

“…For instance, inhibition of about 6% of neurons in the medial prefrontal cortex can suppress drug relapse 36 , and stimulation of as few as 800 AgRP neurons in the arcuate hypothalamus can drive food intake 37 . In another study, direct optogenetic stimulation of small ensembles of basolateral amygdala neurons, with either sucrose or quinine responsivity, could alter consummatory behavior 38 . Together these findings emphasize the increasing recognition of the power of small neuronal ensembles in shaping behavior.…”

Bicistronic Expression of a High-Performance Calcium Indicator and Opsin for All-Optical Stimulation and Imaging at Cellular Resolution

“…Currently, most studies employing all-optical methods for circuit dissection have focused on cortical areas. However, holographic stimulation can be used to investigate network function in other brain regions, as in the olfactory bulb ( Gill et al, 2020 ) or the basolateral amygdala ( Piantadosi et al, 2022 ). While viral tropisms may affect whether any given virus that works well in the cortex also works well in other brain regions, bicistronic delivery methods of both opsin and indicator will simplify testing of expression strategies.…”

The representational geometry of emotional states in basolateral amygdala

“…These locally activated and inactivated neurons may have a variety of response properties. Advancement in multiphoton techniques that allow the simultaneous perturbation and recording of activity-defined ensembles in the BLA can help shed light on mechanisms at the microcircuit level 53 .…”