, 2010; Portugues and Engert, 2011) provide an opportunity for dissecting the neural mechanism and behavioral relevance of cross-modal modulation. Here, we focus on a sound-evoked escape behavior, which is called C-type fast-start (C-start) due to the “C” shape of the body at the end of the first stage of this behavior (Eaton et al., 2001; Korn and Faber, 2005). The C-start behavior, widely employed

by fish and amphibians (Eaton MK-8776 supplier et al., 2001), is executed through the neural circuit consisting of auditory afferents (VIIIth nerves) and command-like neurons, which are called Mauthner cells (M-cells) (Eaton et al., 2001; Korn and Faber, 2005; Liu and Fetcho, 1999). The spiking activity of Mauthner cells

(M-cells), a pair of large reticulospinal neurons bilaterally located in the rhombomere 4 of the hindbrain, is necessary and sufficient for initiating C-start behavior (Korn and Faber, 2005; Liu and Fetcho, 1999). The C-start behavior is an important audiomotor function for Ivacaftor cost animal survival (Korn and Faber, 2005), and its occurrence can be modulated by environmental context (Burgess and Granato, 2007; Eaton and Emberley, 1991). We hypothesize that the fish may optimize this auditory behavior by combining cues received through other sensory modalities, such as the visual system. In the present study, we first established a behavioral paradigm in which a preceding light flash can enhance sound-evoked C-start behavior in larval zebrafish. We then applied a multidisciplinary approach to dissect the synaptic and circuit mechanism underlying this visual modulation of audiomotor function by combining in vivo whole-cell and unit recordings, behavioral assay, pharmacological

treatment, genetic manipulation, two-photon laser ablation, and neural circuit tracing. We found that a flash presented within 0.2– 0.6 s prior to the sound onset enhances sound-evoked responses of M-cells, resulting in facilitated C-start behavior. At the synaptic level, this visual modulation can be accounted for by the increase in tuclazepam both the signal-to-noise (S/N) ratio of sound-evoked VIIIth nerve spiking activity and the transmission efficacy of synapses formed by VIIIth nerves on M-cells. Furthermore, the visual modulation is abolished by two-photon laser ablation of the caudal hypothalamus (HC), or by genetic impairment of dopamine (DA) synthesis or dopaminergic neuron development in the HC. Consistent with its essential role in the visual modulation, HC dopaminergic neurons exhibit bursting activity in response to flashes. Finally, the activation of D1 dopamine receptors (D1Rs) is required for the visual modulation of audiomotor function.