Brain dysfunction during warming is caused by oxygen limitation in larval zebrafish

Abstract

Understanding animal thermal tolerance is crucial to predict how animals will respond to increasingly warmer temperatures, and to mitigate the impact of the climate change on species survival. Yet, the physiological mechanisms underlying animal thermal tolerance are largely unknown. In this study, we developed a method for measuring upper thermal limit (CTmax) in larval zebrafish (Danio rerio) and found that it occurs at similar temperatures as in adult zebrafish. We discovered that CTmax precedes a transient, heat-induced brain-wide depolarization during heat ramping. By monitoring heart rate, we established that cardiac function is sub-optimal during the period where CTmax and brain depolarization occur. In addition, we found that oxygen availability affects both locomotor neural activity and CTmax during a heat stress. The findings of this study suggest that neural impairment due to limited oxygen availability at high temperatures can cause CTmax in zebrafish.HighlightsLarval zebrafish reach their critical thermal limit (CTmax) at similar temperature as adult zebrafishAcute heat stress causes a brain-wide spreading depolarization near the upper thermal limitCTmax precedes brain-wide depolarizationHeart rate declines at high temperatures but is maintained during CTmax and brain depolarizationNeural activity is impaired prior to CTmax and brain-wide depolarizationOxygen availability in the water affects both CTmax and neural activity

Can temperature-dependent changes in myocardial contractility explain why fish only increase heart rate when exposed to acute warming?

“…However, increases in f H cannot carry on indefinitely, and at a certain point f H plateaus before becoming arrhythmic and dropping back to resting levels just prior to the fish's upper critical temperature ( Farrell et al, 1996 ; Farrell, 2009 ; Gollock et al, 2006 ; Leeuwis et al, 2021 ; Steinhausen et al, 2008 ; Verhille et al, 2013 ). Research indicates that this cardiac collapse is likely the result of a combination of factors, including a loss of ventricular excitability due to disruptions in cardiomyocyte ionic currents ( Haverinen and Vornanen, 2006 , 2020 ), a decrease in the efficiency of mitochondrial oxidative phosphorylation ( Christen et al, 2018 ; Gerber et al, 2020 , 2021 ; Iftikar and Hickey, 2013 ; Penney et al, 2014 ) and, potentially, a loss of nervous function ( Andreassen et al, 2020 ). However, why f H alone is responsible for temperature-dependent increases in Q is not known, especially when experiments where the capacity to increase f H is limited by pharmacological agents (e.g.…”

Research on sablefish (Anoplopoma fimbria) suggests that limited capacity to increase heart function leaves hypoxic fish susceptible to heat waves

“…oxygen consumption, ṀO 2 ) [4,5]. For example, heart rate ( f H ) and cardiac output ( _ Q; the amount of blood pumped per minute) increase with temperature, and cardiac collapse [6][7][8][9][10] and neural impairment [11] appear to be key factors in determining the upper thermal limit of fishes. The occurrence and severity of hypoxia are also increasing with climate change [1,12], and hypoxia often coincides with high temperatures in coastal environments [12,13], including at aquaculture cage-sites [14][15][16].…”

Efficacy of Tricaine (MS-222) and Hypothermia as Anesthetic Agents for Blocking Sensorimotor Responses in Larval Zebrafish

“…Though the effects of cold on neuronal signaling have been described in other animals ( 40 ), to the best of our knowledge, this calcium surge has not been reported for zebrafish elsewhere. However, a spreading depolarization has recently been shown to occur in larval zebrafish exposed to noxious heat ( 41 ), and also following extended (>25 min) mechanical suppression of heartbeat ( 21 ). Spreading depolarization refers to a slow spreading wave of depolarization which travels through the brain, is similar to a seizure, but occurs at a much slower timescale (2–6 mm/min).…”