Atypical Antipsychotic Haloperidol Disrupts Prepulse Inhibition of Acoustic Startle Reflex in Larval Zebrafish

Prepulse inhibition (PPI) in larval zebrafish can be utilized as a behavioral marker for neural dysfunction. In this study, we show that application of pharmacological agents to affect the Mauthner Cell mediated startle movement in response to acoustic stimuli can be used to quantify dysfunction. By establishing a robust protocol, we were able to confirm the effects of numerous pharmacological agents on PPI. We were also able to establish that haloperidol had a negative effect on PPI. This parallels some recent mammalian PPI studies that indicate that haloperidol has mixed effect on PPI. Dose dependent effects, timing, and even the nature of the reductionist zebrafish model may be responsible for this difference. However, the large sample sizes and simple neural circuitry makes the larval zebrafish and excellent model for high throughput screens of psychotropic therapeutic agents

Rapid habituation of a touch-induced escape response in Zebrafish (Danio rerio) Larvae.

Zebrafish larvae have several biological features that make them useful for cellular investigations of the mechanisms underlying learning and memory. Of particular interest in this regard is a rapid escape, or startle, reflex possessed by zebrafish larvae; this reflex, the C-start, is mediated by a relatively simple neuronal circuit and exhibits habituation, a non-associative form of learning. Here we demonstrate a rapid form of habituation of the C-start to touch that resembles the previously reported rapid habituation induced by auditory or vibrational stimuli. We also show that touch-induced habituation exhibits input specificity. This work sets the stage for in vivo optical investigations of the cellular sites of plasticity that mediate habituation of the C-start in the larval zebrafish

Long-term habituation of the C-start escape response in zebrafish larvae

The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning—specifically, long-term habituation (LTH)—of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish’s hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory