Abstract
Optogenetics provides a means to dissect the organization and function of neural circuits. Optogenetics also offers the translational promise of restoring sensation, enabling movement or supplanting abnormal activity patterns in pathological brain circuits. However, the inherent sluggishness of evoked photocurrents in conventional channelrhodopsins has hampered the development of optoprostheses that adequately mimic the rate and timing of natural spike patterning. Here, we explore the feasibility and limitations of a central auditory optoprosthesis by photoactivating mouse auditory midbrain neurons that either express channelrhodopsin-2 (ChR2) or Chronos, a channelrhodopsin with ultra-fast channel kinetics. Chronos-mediated spike fidelity surpassed ChR2 and natural acoustic stimulation to support a superior code for the detection and discrimination of rapid pulse trains. Interestingly, this midbrain coding advantage did not translate to a perceptual advantage, as behavioral detection of midbrain activation was equivalent with both opsins. Auditory cortex recordings revealed that the precisely synchronized midbrain responses had been converted to a simplified rate code that was indistinguishable between opsins and less robust overall than acoustic stimulation. These findings demonstrate the temporal coding benefits that can be realized with next-generation channelrhodopsins, but also highlight the challenge of inducing variegated patterns of forebrain spiking activity that support adaptive perception and behavior.
Highlights
Prostheses that deliver patterned electrical stimulation to retinal ganglion or spiral ganglion processes generally provide superior outcomes than stimulation of low-level brain areas
We addressed discrepancies between neural coding in midbrain and behavioral performance by documenting how high-fidelity temporal codes for optogenetic stimulation in the midbrain were transformed in ostensibly disadvantageous ways at the level of the auditory cortex
To understand more about the accuracy and limitations of temporal coding with optogenetic stimulation of the central auditory pathways, we characterized the temporal response fidelity of midbrain neurons activated by trains of narrow-band noise (NBN) bursts or pulses of light at presentation rates ranging from 20–300 Hz
Summary
Prostheses that deliver patterned electrical stimulation to retinal ganglion or spiral ganglion processes generally provide superior outcomes than stimulation of low-level brain areas (for review see Ref. 9,10). One fundamental problem lies in the fact that light-activated photocurrents are sluggish due to inherently slow channel kinetics in channelrhodopsins, which reduces their ability to deliver long lasting, high-frequency neural stimulation (e.g., above 40 Hz,[13,14]) This limitation is problematic for any attempt to reconstitute sound representations in early stages of the auditory pathway, where temporal modulations in acoustic signals are normally encoded with submillisecond precision at rates as high as several hundred hertz[15,16,17]. We addressed discrepancies between neural coding in midbrain and behavioral performance by documenting how high-fidelity temporal codes for optogenetic stimulation in the midbrain were transformed in ostensibly disadvantageous ways at the level of the auditory cortex These findings support the feasibility of single channel optoprosthetic implants for basic auditory awareness but underscore the need to develop more sophisticated approaches for multi-channel cell type-specific activation for encoding spectrotemporally complex signals such as speech
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