Biology subjects

Sauter, K.

Publications and source records attributed to Sauter, K..

5 recordsLinked to original sources

bioRxiv2023

Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors

Neuromodulatory signaling via G protein-coupled receptor (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. Recent efforts have led to the development of optogenetic tools to induce G protein-mediated signaling, with the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimized the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). We validated these optoDopRs showing that they exhibit high signaling specificity and light sensitivity in vitro. In vivo we detected receptor and cell type-specific effects of dopaminergic signaling in various behaviors including the ability of optoDopRs to rescue loss of the endogenous receptors. This work demonstrates that OptoXRs can enable optical control of neuromodulatory receptor specific signaling in functional and behavioral studies.

neuroscience↗

bioRxiv2022

Temporally extended and reversible neuronal silencing with Aion

Optogenetic silencing allows to reveal the necessity of selected neuronal populations for various neurophysiological functions ranging from specific behaviors to neuronal network activity. An ideal optogenetic silencing tool should be switchable between active and inactive states with precise timing while preserving its activity in the absence of light until switched to an inactive state. Although bistable anion-conducting channelrhodopsins (ACRs) were previously engineered to reach this goal, their conducting state life time was limited to only a few minutes and some ACRs were not fully switchable. Here we report Aion, a bistable ACR displaying a long-lasting open state with a spontaneous closing time constant close to 15 min. Moreover, Aion can be switched between the open and closed state with millisecond precision using blue and orange light, respectively. The long conducting state enables overnight silencing of neurons with minimal light exposure. We further generated trafficking-optimized versions of Aion, which show enhanced membrane localization and allow precisely timed, long-lasting all-optical control of nociceptive responses in larvae of Drosophila melanogaster.

neuroscience↗

bioRxiv2021

Optogenetic silencing of neurotransmitter release with a naturally occurring invertebrate rhodopsin

Information is carried between brain regions through neurotransmitter release from axonal presynaptic terminals. Understanding the functional roles of defined neuronal projection pathways in cognitive and behavioral processes requires temporally precise manipulation of their activity in vivo. However, existing optogenetic tools have low efficacy and off-target effects when applied to presynaptic terminals, while chemogenetic tools are difficult to control in space and time. Here, we show that a targeting-enhanced mosquito homologue of the vertebrate encephalopsin (eOPN3) can effectively suppress synaptic transmission through the Gi/o signaling pathway. Brief illumination of presynaptic terminals expressing eOPN3 triggers a lasting suppression of synaptic output that recovers spontaneously within minutes in vitro as well as in vivo. In freely moving mice, eOPN3-mediated suppression of dopaminergic nigrostriatal afferents leads to an ipsiversive rotational bias. We conclude that eOPN3 can be used to selectively suppress neurotransmitter release at synaptic terminals with high spatiotemporal precision, opening new avenues for functional interrogation of long-range neuronal circuits in vivo.

neuroscience↗

bioRxiv2020

Discrete escape responses are generated by neuropeptide-mediated circuit logic

Animals display a plethora of escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximize chances of survival. We uncovered a somatosensory network in Drosophila larvae that encodes two escape behaviors through input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of the same neuromodulatory hub neurons. These gate harsh touch responses via short Neuropeptide F, but noxious light avoidance via compartmentalized, acute Insulin-like peptide 7 action and cognate Relaxin-family receptor signaling in connected downstream neurons. Peptidergic hub neurons can thus act as central circuit elements for first order processing of converging sensory inputs to gate specific escape responses. One Sentence SummaryCompartment-specific neuropeptide action regulates sensory information processing to elicit discrete escape behavior in Drosophila larvae.

neuroscience↗

bioRxiv2020

BiPOLES: a tool for bidirectional dual-color optogenetic control of neurons

Optogenetic manipulation of neuronal activity has become an indispensable experimental strategy in neuroscience research. A large repertoire of excitatory and inhibitory tools allows precise activation or inhibition of genetically targetable neuronal populations. However, an optogenetic tool for reliable bidirectional control of neuronal activity allowing both up- and downregulation of the same neurons in a single experiment is still missing. Here we report BiPOLES, an optogenetic tool for potent excitation and inhibition of the same population of neurons with light of two different colors. BiPOLES consists of an inhibitory, blue-light-sensitive anion-conducting channelrhodopsin fused to an excitatory, red-light-sensitive cation-conducting channelrhodopsin in a single, trafficking-optimized tandem protein. BiPOLES enables multiple new applications including potent dual-color spiking and silencing of the same neurons in vivo and dual-color optogenetic control of two independent neuronal populations.

neuroscience↗