Emerging strategies for the genetic dissection of gene functions, cell types, and neural circuits in the mammalian brain

2021 ◽  
Author(s):  
Ling Gong ◽  
Xue Liu ◽  
Jinyun Wu ◽  
Miao He
Keyword(s):  
Neural Circuits ◽  
Cell Types ◽  
Mammalian Brain ◽  
Genetic Dissection ◽  
Gene Functions

scholarly journals Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain

2021 ◽  
Vol 101 (1) ◽  
pp. 213-258 ◽  
Author(s):  
Rohini Kuner ◽  
Thomas Kuner
Keyword(s):  
Chronic Pain ◽  
Neural Circuits ◽  
Cell Types ◽  
Mammalian Brain ◽  
Specific Cell ◽  
Dynamic Regulation ◽  
Maladaptive Plasticity ◽  
Pathological Pain ◽  
Dimensions Of Pain ◽  
Cellular Circuits

Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.

scholarly journals Transgenic Silencing of Neurons in the Mammalian Brain by Expression of the Allatostatin Receptor (AlstR)

2009 ◽  
Vol 102 (4) ◽  
pp. 2554-2562 ◽  
Author(s):  
M. Wehr ◽  
U. Hostick ◽  
M. Kyweriga ◽  
A. Tan ◽  
A. P. Weible ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Neural Circuits ◽  
Hippocampal Slices ◽  
Neuronal Cell ◽  
Cell Types ◽  
Mammalian Brain ◽  
Specific Cell ◽  
Membrane Hyperpolarization

The mammalian brain is an enormously complex set of circuits composed of interconnected neuronal cell types. The analysis of central neural circuits will be greatly served by the ability to turn off specific neuronal cell types while recording from others in intact brains. Because drug delivery cannot be restricted to specific cell types, this can only be achieved by putting “silencer” transgenes under the control of neuron-specific promoters. Towards this end we have created a line of transgenic mice putting the Drosophila allatostatin (AL) neuropeptide receptor (AlstR) under the control of the tetO element, thus enabling its inducible expression when crossed to tet-transactivator lines. Mammals have no endogenous AL or AlstR, but activation of exogenously expressed AlstR in mammalian neurons leads to membrane hyperpolarization via endogenous G-protein-coupled inward rectifier K+ channels, making the neurons much less likely to fire action potentials. Here we show that this tetO/AlstR line is capable of broadly expressing AlstR mRNA in principal neurons throughout the forebrain when crossed to a commercially-available transactivator line. We electrophysiologically characterize this cross in hippocampal slices, demonstrating that bath application of AL leads to hyperpolarization of CA1 pyramidal neurons, making them refractory to the induction of action potentials by injected current. Finally, we demonstrate the ability of AL application to silence the sound-evoked spiking responses of auditory cortical neurons in intact brains of AlstR/tetO transgenic mice. When crossed to other transactivator lines expressing in defined neuronal cell types, this AlstR/tetO line should prove a very useful tool for the analysis of intact central neural circuits.

scholarly journals Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures

2010 ◽  
Vol 5 (3) ◽  
pp. 439-456 ◽  
Author(s):  
Feng Zhang ◽  
Viviana Gradinaru ◽  
Antoine R Adamantidis ◽  
Remy Durand ◽  
Raag D Airan ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Brain Structures ◽  
Mammalian Brain

scholarly journals Electrophysiological and Transcriptomic Features Reveal a Circular Taxonomy of Cortical Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejandro Rodríguez-Collado ◽  
Cristina Rueda
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neuronal Dynamics ◽  
Electrophysiological Signals ◽  
Visual Cortex Neurons ◽  
Line Level ◽  
Mouse Visual Cortex ◽  
Different Levels

The complete understanding of the mammalian brain requires exact knowledge of the function of each neuron subpopulation composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre lines. Moreover, the proposed methodology locates other Cre lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.

scholarly journals Electrophysiological and Transcriptomic Features Reveal a Circular Taxonomy of Cortical Neurons

2021 ◽  
Author(s):  
Alejandro Rodríguez-Collado ◽  
Cristina Rueda
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neuronal Dynamics ◽  
Electrophysiological Signals ◽  
Visual Cortex Neurons ◽  
Line Level ◽  
Mouse Visual Cortex ◽  
Different Levels

The complete understanding of the mammalian brain requires exact knowledge of the function of each of the neurons composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types Database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre Lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre Line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre Lines. Moreover, the proposed methodology locates other Cre Lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.

scholarly journals Correction to: Recent Advances in the Genetic Dissection of Neural Circuits in Drosophila

2019 ◽  
Vol 35 (6) ◽  
pp. 1138-1138 ◽  
Author(s):  
Chao Guo ◽  
Yufeng Pan ◽  
Zhefeng Gong
Keyword(s):  
Neural Circuits ◽  
Genetic Dissection ◽  
Recent Advances

scholarly journals MicroRNAs and synaptic plasticity—a mutual relationship

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130515 ◽  
Author(s):  
Ayla Aksoy-Aksel ◽  
Federico Zampa ◽  
Gerhard Schratt
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Abilities ◽  
Neural Circuits ◽  
Cell Activity ◽  
Regulatory Function ◽  
Mammalian Brain ◽  
Regulation Of Transcription ◽  
Control Mechanisms ◽  
Mutual Relationship ◽  
Loss Of Function

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

Neural Circuits for Context Processing in Aversive Learning and Memory

2016 ◽  
Author(s):  
Stephen Maren
Keyword(s):  
Emotional Disorders ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Neural Circuits ◽  
Stress Disorder ◽  
Emotional Responses ◽  
Mammalian Brain ◽  
Post Traumatic Stress ◽  
Context Processing ◽  
Post Traumatic

The nature and properties of emotional expression depend importantly on not only the stimuli that elicit emotional responses, but also the context in which those stimuli are experienced. Deficits in context processing have been associated with a variety of cognitive-emotional disorders, including post-traumatic stress disorder (PTSD). These deficits can be localized to specific neural circuits underlying context processing in the mammalian brain. In particular, the hippocampus has been implicated through numerous animal and human studies to be involved both in normal contextual memory formation, but also in discrimination of trauma-related cues. Decreased hippocampal functioning, as is observed in PTSD, is associated with increased generalization of fear and threat responses as well as deficits in extinction of fear. Understanding context processing offers the opportunity to further understand the biology of PTSD and to target new approaches to therapeutics.

scholarly journals Distinct Transcriptomic Cell Types and Neural Circuits of the Subiculum and Prosubiculum along the Dorsal-Ventral Axis

Cell Reports ◽  
2020 ◽  
Vol 31 (7) ◽  
pp. 107648 ◽  
Author(s):  
Song-Lin Ding ◽  
Zizhen Yao ◽  
Karla E. Hirokawa ◽  
Thuc Nghi Nguyen ◽  
Lucas T. Graybuck ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Cell Types

scholarly journals Illuminating the Neural Circuits Underlying Orienting of Attention

Vision ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 4 ◽  
Author(s):  
Michael Posner ◽  
Cristopher Niell
Keyword(s):  
Animal Models ◽  
Superior Colliculus ◽  
Large Scale ◽  
Neural Circuits ◽  
Cell Types ◽  
Local Networks ◽  
Sensory Stimuli ◽  
Cortical Areas ◽  
Large Scale Networks ◽  
Human Neuroimaging

Human neuroimaging has revealed brain networks involving frontal and parietal cortical areas as well as subcortical areas, including the superior colliculus and pulvinar, which are involved in orienting to sensory stimuli. Because accumulating evidence points to similarities between both overt and covert orienting in humans and other animals, we propose that it is now feasible, using animal models, to move beyond these large-scale networks to address the local networks and cell types that mediate orienting of attention. In this opinion piece, we discuss optogenetic and related methods for testing the pathways involved, and obstacles to carrying out such tests in rodent and monkey populations.

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