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Horii, A.

Publications and source records attributed to Horii, A..

2 recordsLinked to original sources

Orthogonal spectral and temporal envelope representation in auditory cortex

Speech perception relies on two fundamental acoustic components: spectral and temporal. While spectral information is known to be represented in the auditory cortex through tonotopy, how temporal features are organized has remained unclear. Here, by varying rise-ramp steepness and frequencies, we reveal that the steepness of the temporal envelope--a critical cue for phonemes discrimination and sound source perception--is systematically mapped in the mouse auditory cortex. Using widefield calcium imaging, we discovered that the envelope steepness is represented orthogonally to the tonotopic axis, forming a two-dimensional cortical map that mirrors the dual structure of sounds. This organization was observed in primary-like auditory regions but not in higher-order-like areas, indicating distinct auditory processing streams. These findings uncover a principle of cortical organization, suggesting that the auditory cortex encodes sound along two independent axes and thereby provides a neural basis for parallel processing for complex sounds such as speech and natural acoustic environments.

neuroscience↗

Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response

NRF2 is a transcription factor responsible for antioxidant stress responses that is usually regulated in a redox-dependent manner. p62 bodies formed by liquid-liquid phase separation contain Ser349-phosphorylated p62, which participates in the redox-independent activation of NRF2. However, the regulatory mechanism and physiological significance of phosphorylation remain unclear. Herein, we identify ULK1 as a kinase responsible for phosphorylation of p62. ULK1 co-localizes with p62 bodies, and directly interacts with p62. This phosphorylation allows KEAP1 to be retained within p62 bodies, activating NRF2. p62S351E/+ mice are phosphomimetic knock-in mice in which Ser351 corresponding to human Ser349 is replaced by Glu. These mice, but not phosphodefective p62S351A/S351A mice, exhibit NRF2 hyperactivation and growth retardation, the latter caused by malnutrition and dehydration due to obstruction of the esophagus and forestomach secondary to hyperkeratosis. p62S351E/+ mice are a phenocopy of systemic Keap1-knockout mice. Our results expand our understanding of the physiological importance of the redox-independent NRF2 activation pathway and provide new insight into the role of phase separation in this process.

cell biology↗