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Cheng, R.-K.

Publications and source records attributed to Cheng, R.-K..

3 recordsLinked to original sources

Optical inhibition of zebrafish behavior with anion channelrhodopsins

In behavioral analysis, optical electrical silencing provides a way to test neuronal necessity. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown--in neuronal culture and in Drosophila--to inhibit neurons potently. Here, we test the usefulness of these channels in zebrafish. When the GtACRs were expressed in motor neurons and actuated with blue or green light, fish spontaneous movement was inhibited. In GtACR1-expressing fish, only 3 {micro}W/mm2 of light was sufficient to have an effect; GtACR2, which is poorly trafficked, required stronger illumination. After light offset, GtACR-expressing fish movement increased; this suggested that termination of light-induced neural inhibition may lead to depolarization. Consistent with this, two-photon imaging of spinal neurons showed that intracellular calcium also increased following light offset. The activity elicited at light offset needs to be taken into consideration in experimental design, although this property may help provide insight into the effects of stimulating a circuit transiently. These results show that GtACR1 and GtACR2 can be used to optically inhibit neurons in zebrafish, and thus to test neural circuit necessity.

neuroscience

Familiarity with companions aids recovery from fear inzebrafish

Interaction with social partners during or after a stressful episode aids recovery in humans and other mammals. We asked if a comparable phenomenon exists in zebrafish (Danio rerio) that live in shoals in the wild. In the first experiment, we observed that most quantifiable parameters of swimming behavior were similar when zerbafish swam alone or with companions. However, after exposure to an alarm substance (Schreckstoff), individuals recovering alone continued to display behaviors associated with fear after removal of the stimulus, while those recovering with companions did not. In the next two experiments, we examined the role of familiarity of companions. Subjects spent more time in the vicinity of familiar companions in a two-choice assay. While both familiar and unfamiliar companions reduced behavioral signs of distress, familiar companions additionally modulated cortisol and endogenous isotocin in subjects. Shortly after being united with familiar companions, isotocin spiked followed by a dampening of circulating cortisol levels. These results suggest that zebrafish experience fear attenuation in the presence of others and familiar companions are more effective at buffering the stress associated with escaping predation. Changes in behavior, circulating cortisol and isotocin levels due to social partners are reminiscent of changes due to amelioration of fear in some mammalian species in the presence of companions. The two phenomena may be related.

animal behavior and cognition

Loss of the habenula neuromodulator Kisspeptin1 disrupts learning

Learning how to actively avoid a predictable aversive stimulus involves two steps: recognizing the cue that predicts upcoming punishment, and learning a behavioral response that will lead to avoidance. In zebrafish, ventral habenula (vHb) neurons have been proposed to participate in both steps by encoding the expected aversiveness of a stimulus. vHb neurons increase their firing rate as expectation of punishment grows, but reduce their activity as avoidance learning occurs. How the change in vHb activity occurs is not known. Here, we ask whether the neuromodulator kisspeptin1, which is expressed in the ventral habenula, could be involved. Kiss1 mutants were generated with Cas9 using guide RNAs targeted to the signal sequence. Mutants, which have a stop codon upstream of the kisspeptin1 peptide, have a deficiency in learning to avoid a shock that is predicted by light. Electrophysiology indicates that kisspeptin1 has a concentration-dependent effect on vHb neurons: depolarizing at low concentrations and hyperpolarizing at high concentrations. These data suggest that as the fish learns to cope with a threat, kisspeptin1 may differentially modulate vHb neurons. This implies that learning a behavioral strategy to overcome a stressor is accompanied by physiological change in habenula neurons.\n\nSignificance statementLearning to deal with adversity can positively affect ones ability to cope with challenges in the immediate future. Control thus causes short-term change in the brain. Here, we show that the neuromodulator kisspeptin1 is required to learn to avoid a punishment. Expression and electrophysiological recordings suggest that this molecule functions by controlling the ventral habenula, a region of the brain that mediates fear by regulating serotonin release. Kisspeptin1 may be a potential player in resilience developed as a result of control, extending previous findings that it can reduce fear.

animal behavior and cognition