No abstract

Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington's nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (Bar), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of Bar neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.

The transient receptor potential A1 (TRPA1) channel is an evolutionarily conserved detector of temperature and irritant chemicals. Here, we show that two specific isoforms of TRPA1 in Drosophila are H 2 O 2 sensitive and that they can detect strong UV light via sensing light-induced production of H 2 O 2 . We found that ectopic expression of these H 2 O 2 -sensitive Drosophila TRPA1 (dTRPA1) isoforms conferred UV sensitivity to light-insensitive HEK293 cells and Drosophila neurons, whereas expressing the H 2 O 2 -insensitive isoform did not. Curiously, when expressed in one specific group of motor neurons in adult flies, the H 2 O 2 -sensitive dTRPA1 isoforms were as competent as the blue light-gated channelrhodopsin-2 in triggering motor output in response to light. We found that the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the adipokinetic hormone (AKH) in the larval ring gland endogenously express these H 2 O 2 -sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC cells required dTRPA1 and H 2 O 2 production but not conventional phototransduction molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV light via photochemical production of H 2 O 2 . We speculate that UV sensitivity conferred by these isoforms in CC cells may allow young larvae to activate stress response-a function of CC cells-when they encounter strong UV, an aversive stimulus for young larvae.UV sensing | dTRPA1 isoforms | reactive oxygen species | Drosophila | optogenetics

It is believed that human primary visual cortex (V1) increases activity with increasing temporal frequency of a visual stimulus. Two kinds of visual stimulus were used in the previous studies, one is patterned-flash stimulus with a fixed onset period and an increasing average luminance with the increase of temporal frequency, the other is contrast reversing flickering checkerboard or grating with a constant average luminance across different temporal frequencies. That hemodynamic responses change as a function of reversal frequency of contrast reversing checkerboard is at odds with neurophysiological studies in animals and neuroimaging studies in humans. In the present study, we addressed the relationship between reversal frequency of contrast reversing checkerboard and hemodynamic response in human V1 using an event-related experimental paradigm and found that the transient characteristics of blood oxygenation level dependent response in human V1 depended very little on the reversal frequency of a contrast reversing checkerboard.