Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos

When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)−expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-μm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system.

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Faculty Opinions recommendation of Optogenetic stimulation of a hippocampal engram activates fear memory recall.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14256961.15779281 ◽

2012 ◽

Author(s):

Ted Abel ◽

Robbert Havekes

Keyword(s):

Fear Memory ◽

Memory Recall ◽

Optogenetic Stimulation ◽

Stimulation Of

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Faculty Opinions recommendation of Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738143860.793576394 ◽

2020 ◽

Author(s):

Gerd Kempermann

Keyword(s):

Optogenetic Stimulation ◽

Stimulation Of

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Incerto-thalamic modulation of fear via GABA and dopamine

Neuropsychopharmacology ◽

10.1038/s41386-021-01006-5 ◽

2021 ◽

Author(s):

Archana Venkataraman ◽

Sarah C. Hunter ◽

Maria Dhinojwala ◽

Diana Ghebrezadik ◽

JiDong Guo ◽

...

Keyword(s):

Brain Regions ◽

Zona Incerta ◽

Dependent Manner ◽

Post Traumatic Stress ◽

Functional Roles ◽

Functional Connections ◽

Optogenetic Stimulation ◽

Fear Generalization ◽

Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

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