Computational algorithm for assessing inter-neuronal connectivity to optimize optogenetic stimulation and neural circuit activity (Conference Presentation)

Author(s):  
Carlos Renteria ◽  
Shreya M. Santhanam ◽  
Yuan-Zhi Liu ◽  
Denise Medina ◽  
Parijat Sengupta ◽  
...  
Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.


2019 ◽  
Author(s):  
Daniel A. Lee ◽  
Grigorios Oikonomou ◽  
Tasha Cammidge ◽  
Young Hong ◽  
David A. Prober

ABSTRACTAlthough several sleep-regulating neurons have been identified, little is known about how they interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we use zebrafish to describe a neural circuit in which neuropeptide VF (npvf)-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and activate serotonergic RN neurons. We additionally demonstrate that optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and is abolished when the RN are ablated or lack serotonin. Finally, genetic epistasis demonstrates that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain circuit for sleep/wake control.


PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205386 ◽  
Author(s):  
Michael Avery ◽  
Jonathan Nassi ◽  
John Reynolds

2021 ◽  
Vol 7 (33) ◽  
pp. eabd9465
Author(s):  
Shahabeddin Vahdat ◽  
Arjun Vivek Pendharkar ◽  
Terrance Chiang ◽  
Sean Harvey ◽  
Haruto Uchino ◽  
...  

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.


2015 ◽  
Vol 27 (10) ◽  
pp. 2011-2038 ◽  
Author(s):  
John J. Hopfield

In higher animals, complex and robust behaviors are produced by the microscopic details of large structured ensembles of neurons. I describe how the emergent computational dynamics of a biologically based neural network generates a robust natural solution to the problem of categorizing time-varying stimulus patterns such as spoken words or animal stereotypical behaviors. The recognition of these patterns is made difficult by their substantial variation in cadence and duration. The neural circuit behaviors used are similar to those associated with brain neural integrators. In the larger context described here, this kind of circuit becomes a building block of an entirely different computational algorithm for solving complex problems. While the network behavior is simulated in detail, a collective view is essential to understanding the results. A closed equation of motion for the collective variable describes an algorithm that quantitatively accounts for many aspects of the emergent network computation. The feedback connections and ongoing activity in the network shape the collective dynamics onto a reduced dimensionality manifold of activity space, which defines the algorithm and computation actually performed. The external inputs are weak and are not the dominant drivers of network activity.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia Zhang ◽  
Dan Chen ◽  
Patrick Sweeney ◽  
Yunlei Yang

AbstractIt is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. However, the feeding circuit for the VMH regulation of food intake remains to be defined. Here, we combine fiber photometry, chemo/optogenetics, virus-assisted retrograde tracing, ChR2-assisted circuit mapping and behavioral assays to show that selective activation of VMH neurons expressing steroidogenic factor 1 (SF1) rapidly inhibits food intake, VMH SF1 neurons project dense fibers to the paraventricular thalamus (PVT), selective chemo/optogenetic stimulation of the PVT-projecting SF1 neurons or their projections to the PVT inhibits food intake, and chemical genetic inactivation of PVT neurons diminishes SF1 neural inhibition of feeding. We also find that activation of SF1 neurons or their projections to the PVT elicits a flavor aversive effect, and selective optogenetic stimulation of ChR2-expressing SF1 projections to the PVT elicits direct excitatory postsynaptic currents. Together, our data reveal a neural circuit from VMH to PVT that inhibits food intake.


2020 ◽  
Author(s):  
Richard J. Kopchock ◽  
Bhavya Ravi ◽  
Addys Bode ◽  
Kevin M. Collins

AbstractSuccessful execution of behavior requires the coordinated activity and communication between multiple cell types. Studies using the relatively simple neural circuits of invertebrates have helped to uncover how conserved molecular and cellular signaling events shape animal behavior. To understand the mechanisms underlying neural circuit activity and behavior, we have been studying a simple circuit that drives egg-laying behavior in the nematode worm C. elegans. Here we show that the female-specific, Ventral C (VC) motoneurons are required for vulval muscle contractility and egg laying in response to serotonin. Ca2+ imaging experiments show the VCs are active during times of vulval muscle contraction and vulval opening, and optogenetic stimulation of the VCs promotes vulval muscle Ca2+ activity. However, while silencing of the VCs does not grossly affect steady-state egg-laying behavior, VC silencing does block egg laying in response to serotonin and increases the failure rate of egg-laying attempts. Signaling from the VCs facilitates full vulval muscle contraction and opening of the vulva for efficient egg laying. We also find the VCs are mechanically activated in response to vulval opening. Optogenetic stimulation of the vulval muscles is sufficient to drive VC Ca2+ activity and requires muscle contractility, showing the presynaptic VCs and the postsynaptic vulval muscles can mutually excite each other. Together, our results demonstrate that the VC neurons facilitate efficient execution of egg-laying behavior by coordinating postsynaptic muscle contractility in response to serotonin and mechanosensory feedback.


Sign in / Sign up

Export Citation Format

Share Document