scholarly journals Use of a Neural Circuit Probe to Validate in silico Predictions of Inhibitory Connections

2017 ◽  
Author(s):  
Honglei Liu ◽  
Daniel Bridges ◽  
Connor Randall ◽  
Sara A. Solla ◽  
Bian Wu ◽  
...  

AbstractUnderstanding how neuronal signals propagate in local network is an important step in understanding information processing. As a result, spike trains recorded with Multi-electrode Arrays (MEAs) have been widely used to study behaviors of neural connections. Studying the dynamics of neuronal networks requires the identification of both excitatory and inhibitory connections. The detection of excitatory relationships can robustly be inferred by characterizing the statistical relationships of neural spike trains. However, the identification of inhibitory relationships is more difficult: distinguishing endogenous low firing rates from active inhibition is not obvious. In this paper, we propose an in silico interventional procedure that makes predictions about the effect of stimulating or inhibiting single neurons on other neurons, and thereby gives the ability to accurately identify inhibitory causal relationships. To experimentally test these predictions, we have developed a Neural Circuit Probe (NCP) that delivers drugs transiently and reversibly on individually identified neurons to assess their contributions to the neural circuit behavior. With the help of NCP, three inhibitory connections identified by our in silico modeling were validated through real interventional experiments. Together, these methods provide a basis for mapping complete neural circuits.

2017 ◽  
Author(s):  
Ivan J. Santiago ◽  
Jing Peng ◽  
Curie Ahn ◽  
Burak Gür ◽  
Katja Sporar ◽  
...  

Laminar arrangement of neural connections is a fundamental feature of neural circuit organization. Identifying mechanisms that coordinate neural connections within correct layers is thus vital for understanding how neural circuits are assembled. In the medulla of the Drosophila visual system neurons form connections within ten parallel layers. The M3 layer receives input from two neuron types that sequentially innervate M3 during development. Here we show that M3-specific innervation by both neurons is coordinated by Drosophila Fezf (dFezf), a conserved transcription factor that is selectively expressed by the earlier targeting input neuron. In this cell, dFezf instructs layer specificity and activates the expression of a secreted molecule (Netrin) that regulates the layer specificity of the other input neuron. We propose that employment of transcriptional modules that cell-intrinsically target neurons to specific layers, and cell-extrinsically recruit other neurons is a general mechanism for building layered networks of neural connections.


2022 ◽  
Author(s):  
Zengpeng Han ◽  
Nengsong Luo ◽  
Jiaxin Kou ◽  
Lei Li ◽  
Wenyu Ma ◽  
...  

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jing Peng ◽  
Ivan J Santiago ◽  
Curie Ahn ◽  
Burak Gur ◽  
C Kimberly Tsui ◽  
...  

Laminar arrangement of neural connections is a fundamental feature of neural circuit organization. Identifying mechanisms that coordinate neural connections within correct layers is thus vital for understanding how neural circuits are assembled. In the medulla of the Drosophila visual system neurons form connections within ten parallel layers. The M3 layer receives input from two neuron types that sequentially innervate M3 during development. Here we show that M3-specific innervation by both neurons is coordinated by Drosophila Fezf (dFezf), a conserved transcription factor that is selectively expressed by the earlier targeting input neuron. In this cell, dFezf instructs layer specificity and activates the expression of a secreted molecule (Netrin) that regulates the layer specificity of the other input neuron. We propose that employment of transcriptional modules that cell-intrinsically target neurons to specific layers, and cell-extrinsically recruit other neurons is a general mechanism for building layered networks of neural connections.


2003 ◽  
Vol 03 (03) ◽  
pp. L275-L287 ◽  
Author(s):  
Dmitry Postnov ◽  
Olga Sosnovtseva ◽  
Dmitry Setsinsky

Dynamical features of neural circuits generating different patterns of spike trains in the presence of noise are investigated: (i) We explore noise-induced multimode dynamics in excitable functional units. Multiple gain of regularity is found to be related to different frequency entrainments and to the appearance of additional time scales; (ii) We develop stochastic implementation of central pattern generator to show that excitable units can successfully replace pacemakers at the appropriate level of noise; (iii) We study the coexistence of beta and gamma rhythms in a local network of nerve cells. It is found that noise can cause coherent switchings between different oscillatory states.


Nature ◽  
2007 ◽  
Vol 448 (7155) ◽  
pp. 802-806 ◽  
Author(s):  
Jaime de la Rocha ◽  
Brent Doiron ◽  
Eric Shea-Brown ◽  
Krešimir Josić ◽  
Alex Reyes

2017 ◽  
Vol 33 (4) ◽  
pp. 331-343
Author(s):  
Erick Javier Argüello Prada ◽  
Ignacio Antonio Buscema Arteaga ◽  
Antonio José D’Alessandro Martínez

2016 ◽  
Author(s):  
Nitin Gupta ◽  
Swikriti Saran Singh ◽  
Mark Stopfer

AbstractOscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly tested this idea in the locust olfactory system. We found that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we found that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrated that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.


Author(s):  
Samantha Hughes ◽  
Tansu Celikel

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.


2005 ◽  
Author(s):  
Marcus Holmberg ◽  
David Gelbart ◽  
Ulrich Ramacher ◽  
Werner Hemmert

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