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 "high road" 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 wellstudied in fish. A "low road" 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 (not shown). 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.

Npas4aexpression in the teleost forebrain is associated with stress coping style differences in fear learning

“…It is made The copyright holder for this preprint this version posted November 25, 2020. ; https://doi.org/10.1101/2020.11.24.396887 doi: bioRxiv preprint Npas4a Expression in Fear Learning ISH analysis showed that npas4a expression was significantly higher in reactive fish in the Dm, Dl, and Vs (Figures 2A-C). The Dm (BLA), Dl (HIP), and Vs (BNST) are key sites of experience-dependent plasticity and integral to fear learning and memory across species (32)(33)(34)(35).…”

“…We then quantified npas4a and gabbr1a forebrain expression to investigate their potential link with differences in conditioned fear responses between alternative stress coping styles. We predict that an increased conditioned fear response in reactive zebrafish will be associated with increased expression of neural plasticity-related genes in the dorsal and medial portions of the dorsal telencephalon (Dm, Dl) and the dorsal, ventral, and supracomissural portions of the ventral telencephalon (Vd, Vv, Vs), putative homologues of the mammalian basolateral amygdala, hippocampus, striatum, lateral septum, and bed nucleus of the stria terminalis, respectively (32)(33)(34)(35).…”

“…More recently other brain regions such as the bed nucleus of the stria terminalis (BNST), lateral septum (LS), and striatum have attracted greater interest due to their functional and structural connections with the hippocampal/amygdala affective forebrain, and their output to structures essential for behavioral and physiological responses to potential threats. The majority of this circuitry has been characterized in rodent models, with putatively homologous structures identified in the teleost forebrain which have also been shown to be critical for contextual fear learning and adaptive responses to stress (32)(33)(34)(35).…”

5-HT2C agonists and antagonists block different components of behavioral responses to potential, distal, and proximal threat in zebrafish

“…In zebrafish, extracellular 5-HT levels were increased after CAS exposure , an effect that can be related to decreased 5-HT uptake (Maximino et al, 2014) and/or decreased monoamine oxidase activity (Lima-Maximino et al, 2020;Quadros et al, 2018). In Crucian carp (Carassius carassius), exposure to CAS elicits increases in serotonergic activity in the brainstem and optic tectum (Höglund et al, 2005), structures which have been involved in responses to distal and proximal threat (do Carmo Silva et al, 2018a). However, this only 3/39 happened when hiding material was unavailable in the tank.…”

“…However, this only 3/39 happened when hiding material was unavailable in the tank. In Nile tilapia (Oreochromis niloticus), CAS did not increase serotonergic activity in the dorsomedial and dorsolateral telencephali (Silva et al, 2015), homologues of the frontotemporal amygdaloid nuclei and hippocampus, respectively (do Carmo Silva et al, 2018a). These results suggest that, during or after exposure, CAS increases serotonergic activity in regions associated with "quick-and-dirty" behavioral responses to distal threat (a "fight/flight/freeze" or "fear" system), but not in the telencephalic areas associated with cautious exploration/risk assessment (a "behavioral inhibition" or "anxiety" system).…”