DPP6 domains responsible for its localization and function.

Dipeptidyl peptidase-like protein 6 (DPP6) is an auxiliary subunit of the Kv4 family of voltage-gated K(+) channels known to enhance channel surface expression and potently accelerate their kinetics. DPP6 is a single transmembrane protein, which is structurally remarkable for its large extracellular domain. Included in this domain is a cysteine-rich motif, the function of which is unknown. Here we show that this cysteine-rich domain of DPP6 is required for its export from the ER and expression on the cell surface. Disulfide bridges formed at C349/C356 and C465/C468 of the cysteine-rich domain are necessary for the enhancement of Kv4.2 channel surface expression but not its interaction with Kv4.2 subunits. The short intracellular N-terminal and transmembrane domains of DPP6 associates with and accelerates the recovery from inactivation of Kv4.2, but the entire extracellular domain is necessary to enhance Kv4.2 surface expression and stabilization. Our findings show that the cysteine-rich domain of DPP6 plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER.

Multiscale temporal integration organizes hierarchical computation in human auditory cortex.

To derive meaning from sound, the brain must integrate information across many timescales. What computations underlie multiscale integration in human auditory cortex? Evidence suggests that auditory cortex analyses sound using both generic acoustic representations (for example, spectrotemporal modulation tuning) and category-specific computations, but the timescales over which these putatively distinct computations integrate remain unclear. To answer this question, we developed a general method to estimate sensory integration windows-the time window when stimuli alter the neural response-and applied our method to intracranial recordings from neurosurgical patients. We show that human auditory cortex integrates hierarchically across diverse timescales spanning from ~50 to 400 ms. Moreover, we find that neural populations with short and long integration windows exhibit distinct functional properties: short-integration electrodes (less than ~200 ms) show prominent spectrotemporal modulation selectivity, while long-integration electrodes (greater than ~200 ms) show prominent category selectivity. These findings reveal how multiscale integration organizes auditory computation in the human brain.

Joint Representation of Spatial and Phonetic Features in the Human Core Auditory Cortex.

The human auditory cortex simultaneously processes speech and determines the location of a speaker in space. Neuroimaging studies in humans have implicated core auditory areas in processing the spectrotemporal and the spatial content of sound; however, how these features are represented together is unclear. We recorded directly from human subjects implanted bilaterally with depth electrodes in core auditory areas as they listened to speech from different directions. We found local and joint selectivity to spatial and spectrotemporal speech features, where the spatial and spectrotemporal features are organized independently of each other. This representation enables successful decoding of both spatial and phonetic information. Furthermore, we found that the location of the speaker does not change the spectrotemporal tuning of the electrodes but, rather, modulates their mean response level. Our findings contribute to defining the functional organization of responses in the human auditory cortex, with implications for more accurate neurophysiological models of speech processing.