Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology

AbstractOptogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.

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Mesencephalic GABA neuronal development: no more on the other side of oblivion

BioMolecular Concepts ◽

10.1515/bmc-2014-0023 ◽

2014 ◽

Vol 5 (5) ◽

pp. 371-382 ◽

Cited By ~ 1

Author(s):

Suyan Li ◽

Sampada Joshee ◽

Anju Vasudevan

Keyword(s):

Transcriptional Control ◽

Neuronal Development ◽

Developmental Regulation ◽

Molecular Characteristics ◽

Psychiatric Illnesses ◽

Neuronal Populations ◽

Gaba Neurons ◽

Recent Developments ◽

And Function ◽

The Brain

AbstractMidbrain GABA neurons, endowed with multiple morphological, physiological and molecular characteristics as well as projection patterns are key players interacting with diverse regions of the brain and capable of modulating several aspects of behavior. The diversity of these GABA neuronal populations based on their location and function in the dorsal, medial or ventral midbrain has challenged efforts to rapidly uncover their developmental regulation. Here we review recent developments that are beginning to illuminate transcriptional control of GABA neurons in the embryonic midbrain (mesencephalon) and discuss its implications for understanding and treatment of neurological and psychiatric illnesses.

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Viral Vector Delivery to Dividing Cells

Contemporary Neuroscience - The Cell Cycle in the Central Nervous System ◽

10.1007/978-1-59745-021-8_33 ◽

2008 ◽

pp. 477-493

Author(s):

Yoshinaga Saeki

Keyword(s):

Viral Vector ◽

Dividing Cells ◽

Vector Delivery

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Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

10.1101/658161 ◽

2019 ◽

Cited By ~ 2

Author(s):

Manxiu Ma ◽

Alexandro D. Ramirez ◽

Tong Wang ◽

Rachel L. Roberts ◽

Katherine E. Harmon ◽

...

Keyword(s):

Animal Model ◽

Light Adaptation ◽

Neural Circuit ◽

Oculomotor System ◽

Gaze Stabilization ◽

Ocular Disorders ◽

Motor Apraxia ◽

Premotor Pathways ◽

And Function ◽

Circuit Function

AbstractDown Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

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Neural contributors to trauma resilience: a review of longitudinal neuroimaging studies

Translational Psychiatry ◽

10.1038/s41398-021-01633-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alyssa R. Roeckner ◽

Katelyn I. Oliver ◽

Lauren A. M. Lebois ◽

Sanne J. H. van Rooij ◽

Jennifer S. Stevens

Keyword(s):

Individual Differences ◽

Neural Circuit ◽

Major Life ◽

Stress Resilience ◽

Control Networks ◽

The Face ◽

Sensory Cortices ◽

Life Stressor ◽

Threat Cues ◽

And Function

AbstractResilience in the face of major life stressors is changeable over time and with experience. Accordingly, differing sets of neurobiological factors may contribute to an adaptive stress response before, during, and after the stressor. Longitudinal studies are therefore particularly effective in answering questions about the determinants of resilience. Here we provide an overview of the rapidly-growing body of longitudinal neuroimaging research on stress resilience. Despite lingering gaps and limitations, these studies are beginning to reveal individual differences in neural circuit structure and function that appear protective against the emergence of future psychopathology following a major life stressor. Here we outline a neural circuit model of resilience to trauma. Specifically, pre-trauma biomarkers of resilience show that an ability to modulate activity within threat and salience networks predicts fewer stress-related symptoms. In contrast, early post-trauma biomarkers of subsequent resilience or recovery show a more complex pattern, spanning a number of major circuits including attention and cognitive control networks as well as primary sensory cortices. This novel synthesis suggests stress resilience may be scaffolded by stable individual differences in the processing of threat cues, and further buttressed by post-trauma adaptations to the stressor that encompass multiple mechanisms and circuits. More attention and resources supporting this work will inform the targets and timing of mechanistic resilience-boosting interventions.

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Perceptual detection depends on spike count integration

10.1101/865410 ◽

2019 ◽

Author(s):

Jackson J. Cone ◽

Morgan L. Bade ◽

Nicolas Y. Masse ◽

Elizabeth A. Page ◽

David J. Freedman ◽

...

Keyword(s):

Neural Networks ◽

Cerebral Cortex ◽

Visual Cortex ◽

Recurrent Neural Networks ◽

Neural Circuit ◽

Visual Detection ◽

Spike Count ◽

Neuronal Responses ◽

Neuronal Populations ◽

And Behavior

AbstractWhenever the retinal image changes some neurons in visual cortex increase their rate of firing, while others decrease their rate of firing. Linking specific sets of neuronal responses with perception and behavior is essential for understanding mechanisms of neural circuit computation. We trained mice to perform visual detection tasks and used optogenetic perturbations to increase or decrease neuronal spiking primary visual cortex (V1). Perceptual reports were always enhanced by increments in V1 spike counts and impaired by decrements, even when increments and decrements were delivered to the same neuronal populations. Moreover, detecting changes in cortical activity depended on spike count integration rather than instantaneous changes in spiking. Recurrent neural networks trained in the task similarly relied on increments in neuronal activity when activity was costly. This work clarifies neuronal decoding strategies employed by cerebral cortex to translate cortical spiking into percepts that can be used to guide behavior.

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Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

eLife ◽

10.7554/elife.22234 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 15

Author(s):

Catherine M Drerup ◽

Amy L Herbert ◽

Kelly R Monk ◽

Alex V Nechiporuk

Keyword(s):

Neural Circuit ◽

Genetic Interaction ◽

Retrograde Transport ◽

Genetic Screen ◽

Binding Domain ◽

Loss Of Function ◽

Mitochondrial Transport ◽

Interaction Studies ◽

Mitochondrial Motility ◽

And Function

Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

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