The Aversive Brain System of Teleosts: Implications for Neuroscience and Biological Psychiatry

Abstract

Defensive behavior is a function of specific survival circuits, the “aversive brain system”, that are thought to be conserved across vertebrates, and involve threat detection and the organization of defensive responses to reduce or eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic subnuclei and midbrain circuits. The increased interest in teleost fishes as model organisms in neuroscience created a demand to understand which brain circuits are involved in defensive behavior. Telencephalic and habenular circuits represent a “forebrain circuit” for threat processing and organization of responses, being important to  mounting appropriate coping responses. Specific hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but are the less well-studied in fish. A “midbrain circuit” is represented by projections to interneurons in the optic tectum which mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Threatening stimuli (especially visual stimuli) can bypass the “high road” and directly activate this system, initiating escape responses. Increased attention to these circuits in an evolutionary framework is still needed.

Functional characterisation of single nucleotide variants of the psychiatric risk gene cacna1c in the zebrafish

“…This observation is similar to what was earlier reported for cacna1c LOF zebrafish larvae [23] and for humans carrying mutations in other neuropsychiatric related genes [59]. The brain circuitry and neurotransmitter systems mediating PPI in mammals are conserved in the zebrafish [63,64].…”

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

“…However, 5‐HT 1A , 5‐HT 2A , and 5‐HT 2C receptors in the dorsolateral periaqueductal gray area have been shown to phasically inhibit escape/fear responses in rats (de Soares & Zangrossi, ). While currently it is unknown whether the griseum centrale, the teleostean homolog of the periaqueductal gray area, is involved in fear responses in zebrafish or not, its anatomical position and hodology suggest so (do Carmo Silva et al, ; Maximino et al, ). Thus, 5‐HT 1A ‐ and 5‐HT 2 ‐like receptors appear to be involved in phasic inhibition of fear‐like behavior, but so far evidence for a tonic inhibition is lacking.…”

“…In non‐mammalian vertebrates, including teleost fish, 5‐HT is produced in additional brain regions, including pretectal and hypothalamic populations (Herculano & Maximino, ). There is some evidence that 5‐HTergic neurons innervate areas of the teleostean brain, which participate in defensive behavior, including prosencephalic and mesencephalic regions (do Carmo Silva, Lima‐Maximino, & Maximino, ). A role for 5‐HT in modulating fish defensive behavior has been demonstrated before: in zebrafish, 5‐HT 1A and 5‐HT 1B receptor antagonists decrease anxiety‐like behavior (Herculano, Puty, Miranda, Lima, & Maximino, ; Maximino, Lima, Jesus Oliveira Batista, Oliveira, & Herculano, ; Maximino et al, ; Nowicki, Tran, Muraleetharan, Markovic, & Gerlai, ), while 5‐HT 2 ‐ and 5‐HT 3 ‐type antagonists increase it (Nowicki et al, ).…”

Visual learning and its underlying neural substrate in two species of teleost fish (Zebrafish and Ambon damselfish)

“…Another structure likely involved in modulating the responses to approaching predators is the medial division of the dorsal pallium (Dm, brown structure in the telencephalon in Figure 2.4). This forebrain structure is viewed as the homolog of the mammalian amygdala (Wullimann and Mueller, 2004;Yamamoto et al, 2007;Mueller et al, 2011) and could therefore participate in responses to aversive stimuli in zebrafish (von Trotha et al, 2014;do Carmo Silva et al, 2018;Lal et al, 2018). The Dm is likely to receive most of its visual information from the preglomerular nucleus (brown relay structure in Figure 2.4).…”