Based on our findings, we propose the following scheme for this visuo-auditory cross-modal modulation (Figure 8C). Ipsilateral visual inputs can selleck compound evoke bursting activity in hypothalamic dopaminergic neurons, possibly leading to dopamine secretion around the area of VIIIth nerve-Mauthner cell circuits, and then exert D1R-dependent neuromodulatory actions within a time window of a few hundred milliseconds on both the VIIIth nerve and its synapses on the

Mauthner cell. These actions include a reduction of spontaneous spiking activity and resultant increased S/N ratio of sound-evoked spiking activity in the VIIIth nerve as well as an increased efficacy of VIIIth nerve-Mauthner cell synapses. These effects cooperatively enhance the sound-evoked responses of Mauthner cells, leading to the enhancement of auditory C-start escape behavior. Thus, by addressing cross-modal modulation from behavioral level to circuit and synaptic level, our study illustrates a cooperative neural mechanism

for visual modulation of audiomotor processing, and reveals a role of dopaminergic system in cross-modal modulation. This Adriamycin mouse two-step cooperative mechanism, i.e., decreasing presynaptic spontaneous activity and increasing downstream synaptic efficacy, represents an efficient strategy to improve signal detection. Obviously, increasing synaptic efficacy alone can increase neural responsivity to sensory stimuli. However, it also inevitably amplifies noise responses, which could be generated by background sensory input or presynaptic spontaneous activity, resulting in increased energy consumption. On the other hand, decreasing spontaneous activity is capable of reducing noise response and thus increases S/N ratio (Foote et al., 1975; Hestrin, 2011; Hurley et al., 2004; Kuo and Trussell, 2011). To our knowledge, the coexistence of these two cooperative mechanisms in single neural circuits has not yet been experimentally

demonstrated. In the present work, we found that decreasing presynaptic noise and increasing downstream synaptic efficacy take place concurrently to enhance the detection of auditory signals. With a preceding light flash, the spontaneous spiking activity Lenalidomide (CC-5013) of VIIIth nerves is significantly suppressed, whereas its sound-evoked activity is less affected. Thus the S/N ratio of sound-evoked spiking activity in the VIIIth nerve is increased by the preceding flash. Besides the increase in S/N ratio, the reduction in presynaptic spontaneous activity may also indirectly increase the efficacy of downstream synaptic transmission by partially removing presynaptically originated short-term depression of sound-evoked responses (Hestrin, 2011; Kuo and Trussell, 2011). This contribution to increase in synaptic efficacy can be limited, because the low spontaneous firing rate of the VIIIth nerve (see Figure 4) restricts the degree of short-term depression.