Multiple convergent hypothalamus–brainstem circuits drive defensive behavior

Abstract

Animals survive environmental challenges by adapting their physiology and behavior through homeostatic regulatory processes, mediated in part by specific neuropeptide release from the hypothalamus. Animals can also avoid environmental stressors within seconds, a fast behavioral adaptation for which hypothalamic involvement is not established. Using brain-wide neural activity imaging in behaving zebrafish, here we find that hypothalamic neurons are rapidly engaged during common avoidance responses elicited by various environmental stressors. By developing methods to register cellular-resolution neural dynamics to multiplexed in situ gene expression, we find that each category of stressor recruits similar combinations of multiple peptidergic cell types in the hypothalamus. Anatomical analysis and functional manipulations demonstrate that these diverse cell types play shared roles in behavior, are glutamatergic, and converge upon spinal-projecting brainstem neurons required for avoidance. These data demonstrate that hypothalamic neural populations, classically associated with slow and specific homeostatic adaptations, also together give rise to fast and generalized avoidance behavior.1 .

Larval zebrafish use olfactory detection of sodium and chloride to avoid salt-water

“…Even the baseline activity in normal fish water is well above the minimal activity during exposure to deionized water. In line with a hypothesis discussed in Lovett-Baron et al 19 , retention of information about the surrounding salinity might be necessary for regulating non-motor related functions. After early attempts to escape salt fail, the animal may still survive if it can hormonally regulate its ion balance.…”

“…Zebrafish in particular, would benefit from the ability to detect and navigate NaCl gradients since the environments in which they likely evolved are characterized by dramatic changes in local salinity levels: the river basins that surround the Ganges River in India and Bangladesh for example 15,16 , are characterized by soft, ion-poor water with NaCl concentrations below 1 part per trillion,which can increase locally by orders of magnitude during the dry season 17 . Importantly, such changes lead to elevated stress and cortisol levels, and are ultimately lethal 18,19,20 , which makes neural mechanisms for detecting and avoiding salt gradients paramount for survival. Here, we show that zebrafish have evolved behavioral strategies to avoid high-salt environments and that this behavior is mediated by the olfactory system through a subset of olfactory sensory neurons that detect the combined presence of sodium and chloride.…”

Larval Zebrafish Use Olfactory Detection of Sodium and Chloride to Avoid Salt Water

“…29 One caveat to this observation is that our light sheet consists of a single beam that is scanned through the left eye of the animal. As such, we have likely missed salinity-related activity within the hypothalamus, as has been previously observed, 22,30 or subtle activity in small nuclei proximal to the eyes (i.e., the trigeminal nucleus). Nonetheless, we do observe a midbrain cluster of units near the dorsal raphe and interpeduncular nucleus (Figure 3F), whose activity patterns share high mutual information with the animal's behavior, as well as the combination of stimulus and behavior (Figures S3A and S3B).…”

“…Zebrafish, in particular, would benefit from the ability to detect and navigate NaCl gradients because the environments in which they likely evolved are characterized by dramatic changes in local salinity levels: the river basins that surround the Ganges River in India and Bangladesh, for example, 17,18 are characterized by soft, ion-poor water with NaCl concentrations as low as 1 part per trillion, which can increase locally by orders of magnitude during the dry season. 19 Importantly, such changes lead to elevated stress and cortisol levels and are ultimately lethal, [20][21][22] which makes neural mechanisms for detecting and avoiding salt gradients paramount for survival. Here, we show that zebrafish have evolved behavioral strategies to avoid highsalt environments and that this behavior is mediated by the olfactory system through a subset of olfactory sensory neurons that detect the combined presence of sodium and chloride.…”

A neural circuit basis for binasal input-enhanced chemosensory avoidance

“…These include chemosensory behaviors, alongside phototaxis, oculomotor and optokinetic responses, prey capture and various escape responses (Kalueff et al, 2013; Loring et al, 2020). With a relatively small, transparent brain that comprises a more tractable number of neurons (~10 5 ), much has been learnt about the circuitries mediating sensory processing and sensorimotor behaviors in larval zebrafish (Ahrens et al, 2012; Bahl and Engert, 2020; Chen et al, 2018; Dragomir et al, 2020; Fernandes et al, 2020; Gebhardt et al, 2019; Haesemeyer et al, 2018; Herrera et al, 2020; Kawashima et al, 2016; Knogler et al, 2017; Lacoste et al, 2015; Lovett-Barron et al, 2020; Migault et al, 2018; Naumann et al, 2016; Portugues et al, 2014; Vanwalleghem et al, 2020; Wee et al, 2019; Wolf et al, 2017; Yao et al, 2016; Zhang et al, 2017). Larval zebrafish also offers a unique opportunity for studying the brainwide organizational principles of neural circuits mediating bilateral sensory input integration.…”