Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

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The STROBE: a system for closed-looped optogenetic control of freely feeding flies

10.1101/486050 ◽

2018 ◽

Author(s):

Pierre-Yves Musso ◽

Pierre Junca ◽

Meghan Jelen ◽

Damian Feldman-Kiss ◽

Han Zhang ◽

...

Keyword(s):

Sensory Neurons ◽

Dopaminergic Neurons ◽

Mushroom Body ◽

Internal State ◽

Feeding Behaviors ◽

Optogenetic Stimulation ◽

Freely Moving ◽

Neural Excitation ◽

Stimulation Of ◽

Feeding Circuits

AbstractManipulating feeding circuits in freely moving animals is challenging, in part because the timing of sensory inputs is affected by the animal’s behavior. To address this challenge in Drosophila, we developed the Sip-Triggered Optogenetic Behavior Enclosure (“STROBE”). The STROBE is a closed-looped system for real-time optogenetic activation of feeding flies, designed to evoke neural excitation coincident with food contact. We demonstrate that optogenetic stimulation of sweet sensory neurons in the STROBE drives attraction to tasteless food, while activation of bitter sensory neurons promotes avoidance. Moreover, feeding behavior in the STROBE is modified by the fly’s internal state, as well as the presence of chemical taste ligands. We also find that mushroom body dopaminergic neurons and their respective post-synaptic partners drive opposing feeding behaviors following activation. Together, these results establish the STROBE as a new tool for dissecting fly feeding circuits and suggest a role for mushroom body circuits in processing naïve taste responses.

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Coordination of brain wide activity dynamics by dopaminergic neurons

10.1101/042168 ◽

2016 ◽

Author(s):

Garret Stuber ◽

Heather Decot ◽

Vijay Namboodiri ◽

Wei Gao ◽

Jenna McHenry ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Large Scale ◽

Cerebral Blood Volume ◽

Brain Activity ◽

Functional Magnetic Resonance ◽

Transgenic Rats ◽

Optogenetic Stimulation ◽

The Brain ◽

Neuropsychiatric Conditions ◽

Stimulation Of

Several neuropsychiatric conditions, such as addiction, schizophrenia, and depression may arise in part from dysregulated activity of ventral tegmental area dopaminergic (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. However, whether THVTA activity affects large-scale brain-wide function remains unknown. Here, we selectively activated THVTA neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging (fMRI). Selective optogenetic stimulation of THVTA neurons not only enhanced cerebral blood volume (CBV) signals in striatal target regions in a dopamine receptor dependent fashion, but also engaged many additional anatomically defined regions throughout the brain. In addition, repeated pairing of THVTA neuronal activity with forepaw stimulation, produced an expanded brain-wide sensory representation. These data suggest that modulation of THVTA neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTA input.

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High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

10.1101/051912 ◽

2016 ◽

Cited By ~ 1

Author(s):

Christopher P Burgess ◽

Armin Lak ◽

Nicholas A Steinmetz ◽

Peter Zatka-Haas ◽

Charu Bai Reddy ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Visual Stimulation ◽

Mammalian Species ◽

High Yield ◽

Steering Wheel ◽

Neural Basis ◽

Two Photon ◽

Optogenetic Stimulation ◽

Observer Model ◽

Mouse Vision

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis.

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