Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat

Area of Science:

• Neuroscience
• Behavioral Biology

Background:

• Calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) are implicated in processing aversive information and signaling general alarm.
• Prior research primarily focused on CGRP neurons' role in passive defensive behaviors (e.g., freezing), with limited understanding of their involvement in active defense.

Purpose of the Study:

• To investigate the role of PBN CGRP neurons in active defensive behaviors, specifically flight responses.
• To determine if CGRP neuron activation modulates active defense based on threat intensity and context.

Main Methods:

• Utilized a predator-like robot to elicit active defensive behaviors (chasing) in mice.
• Employed electrophysiology to record CGRP neuron activity during aversive stimulus presentation.
• Used optogenetics to activate or inactivate PBN CGRP neurons during predator robot encounters.

Main Results:

• CGRP neurons encode aversive stimulus intensity through firing duration and amplitude.
• Optogenetic activation of CGRP neurons increased flight responses to the robot.
• Inactivation of CGRP neurons reduced flight responses, even to highly threatening stimuli.

Conclusions:

• PBN CGRP neurons function as a critical alarm system that dynamically regulates active defensive behaviors.
• These neurons amplify threat perception, facilitating adaptive responses to varying danger levels.
• Findings expand the known functions of CGRP neurons beyond passive defense mechanisms.