Neural correlates of state transitions elicited by a chemosensory danger cue

Abstract

BackgroundDetection of predator cues changes the brain state in prey species and helps them avoid danger. Dysfunctionality in changing the central state appropriately in stressful situations is proposed to be an underlying cause of multiple psychiatric disorders in humans. MethodsHere, we investigate the dynamics of neural circuits mediating response to a threat, to characterize these states and to identify potential control networks. We use resonant scanning 2-photon microscopy for in vivo brain-wide imaging and custom designed behavioral assays for the study. ResultsWe first show that 5-7 day old zebrafish larvae react to an alarm pheromone (Schreckstoff ) with reduced mobility. They subsequently display heightened vigilance, as evidenced by increased dark avoidance. Calcium imaging indicates that exposure to Schreckstoff elicits stimulus-locked activity in olfactory sensory neurons innervating a lateral glomerulus and in telencephalic regions including the putative medial amygdala and entopeduncular nucleus. Sustained activity outlasting the stimulus delivery was detected in regions regulating neuromodulator release, including the lateral habenula, posterior tuberculum, superior raphe, and locus coeruleus. 1/15.

Specialized neurons in the right habenula mediate response to aversive olfactory cues

“…Through calcium imaging using a genetically encoded calcium indicator, we validated that the right dHb is responsive when larval zebrafish are exposed to aversive odors such as cadaverine or chondroitin sulfate ( Jetti et al, 2014 ; Krishnan et al, 2014 ), a component of alarm substance ( Mathuru et al, 2012 ), more specifically, that the lratd2a -expressing neurons of the right dHb significantly respond to these aversive olfactory cues above their response to water alone. As has also been observed by others ( Jesuthasan et al, 2021 ), application of vehicle alone, even when introduced slowly into a testing chamber, is sufficient to elicit a change in GCaMP fluorescence.…”

Specialized neurons in the right habenula mediate response to aversive olfactory cues

“…From calcium imaging, we validated that the right dHb appears more responsive than the left when larval zebrafish are exposed to aversive odors such as cadaverine or chondroitin sulfate (Jetti et al, 2014;Krishnan et al, 2014), a component of alarm substance (Mathuru et al, 2012), and further determined that the lratd2a-expressing neurons of the right dHb specifically respond to these aversive olfactory cues. As has also been observed by others (Jesuthasan et al, 2020), application of vehicle alone, even when introduced slowly into a testing chamber, is sufficient to elicit a change in GCaMP fluorescence. Determining the habenular response to odorants relative to vehicle alone is thus an essential measure, but one that has not been reported in all studies (Chen et al, 2019;Jetti et al, 2014;Krishnan et al, 2014).…”

Collective behavior emerges from genetically controlled simple behavioral motifs in zebrafish

“…Although fish have many sensory inputs that likely contribute to group behaviors, zebrafish are highly visual ( 39 , 41 , 46 ), suggesting that visual drives likely play a dominant role. Other sensory modalities, such as somatosensation through the lateral line ( 32 , 33 ) and olfaction ( 26 , 34 ), undoubtedly play roles in modulating social interactions, as might currently less decipherable elements such as “internal state” ( 25 – 27 ) and “personality” ( 28 – 31 ).…”