Serotonergic modulation of startle-escape plasticity in an African cichlid fish: a single-cell molecular and physiological analysis of a vital neural circuit

Abstract

Whitaker KW, Neumeister H, Huffman LS, Kidd CE, Preuss T, Hofmann HA. Serotonergic modulation of startle-escape plasticity in an African cichlid fish: a single-cell molecular and physiological analysis of a vital neural circuit. J Neurophysiol 106: 127-137, 2011. First published March 30, 2011 doi:10.1152/jn.01126.2010.-Social life affects brain function at all levels, including gene expression, neurochemical balance, and neural circuits. We have previously shown that in the cichlid fish Astatotilapia burtoni brightly colored, socially dominant (DOM) males face a trade-off between reproductive opportunities and increased predation risk. Compared with camouflaged subordinate (SUB) males, DOMs exposed to a loud sound pip display higher startle responsiveness and increased excitability of the Mauthner cell (M-cell) circuit that governs this behavior. Using behavioral tests, intracellular recordings, and single-cell molecular analysis, we show here that serotonin (5-HT) modulates this socially regulated plasticity via the 5-HT receptor subtype 2 (5-HTR 2 ). Specifically, SUBs display increased sensitivity to pharmacological manipulation of 5-HTR 2 compared with DOMs in both startle-escape behavior and electrophysiological properties of the M-cell. Immunohistochemistry showed serotonergic varicosities around the M-cells, further suggesting that 5-HT impinges directly onto the startle-escape circuitry. To determine whether the effects of 5-HTR 2 are pre-or postsynaptic, and whether other 5-HTR subtypes are involved, we harvested the mRNA from single M-cells via cytoplasmic aspiration and found that 5-HTR subtypes 5A and 6 are expressed in the M-cell. 5-HTR 2 , however, was absent, suggesting that it affects M-cell excitability through a presynaptic mechanism. These results are consistent with a role for 5-HT in modulating startle plasticity and increase our understanding of the neural and molecular basis of a trade-off between reproduction and predation.Mauthner cell; single-cell polymerase chain reaction; Astatotilapia burtoni; 5-HT receptor subtype 2; ketanserin BRAIN AND BEHAVIOR ARE SCULPTED by an intricate and dynamic interplay between genotype, prior experience, and an individual's current social and physiological state (Hofmann 2003;Robinson et al. 2008;

The Activity of Isolated Neurons and the Modulatory State of an Isolated Nervous System Represent a Recent Behavioural State

“…Recent reports demonstrating that behavioural state induced changes in receptor gene expression (Whitaker et al, 2011), neuronal response to neurotransmitters (Yeh et al, 1996;Edwards et al, 2002) and in neurotransmitter synthesis (Hatcher et al, 2008) at the single-cell level are in line with this point of view as well.…”

Neural Circuit Reconfiguration by Social Status

“…Status-dependent circuit reconfiguration in other species may result from proximate mechanisms similar to those described in crayfish, including changes in modulatory function, neuronal thresholds, and the gain or sign of synaptic function (Yeh et al, 1996;Krasne et al, 1997;Herberholz et al, 2001). Indeed, as in crayfish (Yeh et al, 1996;Cattaert et al, 2010), the status-dependent changes in Mauthner excitability have been linked to status-dependent changes in serotonergic modulation (Whitaker et al, 2011). Other proximate mechanisms may result from the kinds of status-related differences in the nervous system already observed in many animals, including transmitter or neuromodulator concentration (Gutzler et al, 2010), receptor populations (Spitzer et al, 2005;Burmeister et al, 2007), changes in neuronal size and shape (White et al, 2002), neurogenesis (Kozorovitskiy and Gould, 2004;Song et al, 2007), and gross brain morphology (Holmes et al, 2007;O'Donnell et al, 2007).…”

“…Social status affects neurogenesis in rodents (Kozorovitskiy and Gould, 2004) and crayfish (Song et al, 2007), neuronal size in fish (White et al, 2002), brain morphology in wasps (O'Donnell et al, 2007) and naked mole rats (Holmes et al, 2007), and cell receptor populations in crayfish (Spitzer et al, 2005) and fish (Burmeister et al, 2007). Social status also affects the serotonergic neuromodulation of synaptic responses in both crayfish (Yeh et al, 1996(Yeh et al, , 1997 and fish (Whitaker et al, 2011), and the excitability of neural circuits that produce different behaviors (Krasne et al, 1997;Herberholz et al, 2001;Neumeister et al, 2010). It remains unclear, however, how neural circuits are altered to produce status-dependent behavioral responses.…”

Fear is the mother of invention: anuran embryos exposed to predator cues alter life-history traits, post-hatching behaviour, and neuronal activity patterns

“…It is well known that developing embryos and tadpoles modify the timing of hatching/ metamorphosis as well as morphology and behaviour in response to the perception of chemical cues of predation (Van Buskirk, 2001;Laurila et al, 2002;Orizaola and Braña, 2004;Ireland et al, 2007;Ferrari and Chivers, 2009;, and this plasticity may result in increased survival (Mathis et al, 2008). In contrast, the neurophysiological changes underlying phenotypic behavioural plasticity induced by predator cues remain largely unexplored (Orr et al, 2007;Whitaker et al, 2011). Predator odours processed through the olfactory neural system may, for example, modulate the hypothalamo-pituitary-adrenocortical axis and hence corticosteroid production, which in turn mediates life-history, morphological and behavioural changes in tadpoles (Denver, 2009;Maher et al, 2013).…”