scholarly journals High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis

2016 ◽  
Vol 115 (6) ◽  
pp. 3204-3216 ◽  
Author(s):  
Xiangmin Xu ◽  
Taruna Ikrar ◽  
Yanjun Sun ◽  
Rommel Santos ◽  
Todd C. Holmes ◽  
...  
Keyword(s):  
High Resolution ◽  
Functional Organization ◽  
Stria Terminalis ◽  
Cell Type ◽  
Experimental Conditions ◽  
Bed Nucleus ◽  
Local Circuit ◽  
Synaptic Inputs ◽  
Cell Type Specific ◽  
Local Circuits

The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types.

scholarly journals Opiate dependence induces cell type-specific plasticity of intrinsic membrane properties in the rat juxtacapsular bed nucleus of stria terminalis (jcBNST)

2017 ◽  
Vol 234 (23-24) ◽  
pp. 3485-3498 ◽  
Author(s):  
Walter Francesconi ◽  
Attila Szücs ◽  
Fulvia Berton ◽  
George F. Koob ◽  
Leandro F. Vendruscolo ◽  
...  
Keyword(s):  
Opiate Dependence ◽  
Membrane Properties ◽  
Stria Terminalis ◽  
Cell Type ◽  
Bed Nucleus ◽  
Cell Type Specific ◽  
Intrinsic Membrane Properties

Anxiety-related cell-type-specific neural circuits in the anterior-dorsal bed nucleus of the stria terminalis

2020 ◽  
Vol 65 (14) ◽  
pp. 1203-1216 ◽  
Author(s):  
Xinxin Wang ◽  
Yongsheng Zhang ◽  
Xu Wang ◽  
Jiaqi Dai ◽  
Ruifang Hua ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Stria Terminalis ◽  
Cell Type ◽  
Bed Nucleus ◽  
Anterior Dorsal ◽  
Related Cell ◽  
Cell Type Specific

scholarly journals Genetic engineering for in vivo optical interrogation of neuronal responses to cell type-specific silencing

2021 ◽  
Author(s):  
Firat Terzi ◽  
Johannes Knabbe ◽  
Sidney B. Cambridge
Keyword(s):  
High Resolution ◽  
Genetic Engineering ◽  
Transgene Expression ◽  
Neuronal Morphology ◽  
Dependent Manner ◽  
Cell Type ◽  
Fluorescent Marker ◽  
Genetic Perturbations ◽  
Cell Type Specific

SummaryGenetic engineering of quintuple transgenic brain tissue was used to establish a low background, Cre-dependent version of the inducible Tet-On system for fast, cell type-specific transgene expression in vivo. Co-expression of a constitutive, Cre-dependent fluorescent marker selectively allowed single cell analyses before and after inducible, tet-dependent transgene expression. Here, we used this method for acute, high-resolution manipulation of neuronal activity in the living brain. Single induction of the potassium channel Kir2.1 produced cell type-specific silencing within hours that lasted for at least three days. Longitudinal in vivo imaging of spontaneous calcium transients and neuronal morphology demonstrated that prolonged silencing did not alter spine densities or synaptic input strength. Furthermore, selective induction of Kir2.1 in parvalbumin interneurons increased the activity of surrounding neurons in a distance-dependent manner. This high-resolution, inducible interference and interval imaging of individual cells (high I5, ‘HighFive’) method thus allows visualizing temporally precise, genetic perturbations of defined cells.

scholarly journals Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis

2019 ◽  
Vol 150 ◽  
pp. 80-90 ◽  
Author(s):  
Sarah E. Daniel ◽  
Aurélie Menigoz ◽  
Jidong Guo ◽  
Steven J. Ryan ◽  
Shivani Seth ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Stria Terminalis ◽  
Cell Type ◽  
Bed Nucleus

scholarly journals Differential effects of static and dynamic inputs on neuronal excitability

2015 ◽  
Vol 113 (1) ◽  
pp. 232-243 ◽  
Author(s):  
Attila Szücs ◽  
Ramon Huerta
Keyword(s):  
Neuronal Excitability ◽  
Computational Study ◽  
Ionic Currents ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Synaptic Inputs ◽  
Cation Current ◽  
Excitability Of Neurons ◽  
Inwardly Rectifying ◽  
Activity Dependent

The intrinsic excitability of neurons is known to be dynamically regulated by activity-dependent plasticity and homeostatic mechanisms. Such processes are commonly analyzed in the context of input-output functions that describe how neurons fire in response to constant levels of current. However, it is not well understood how changes of excitability as observed under static inputs translate to the function of the same neurons in their natural synaptic environment. Here we performed a computational study and hybrid experiments on rat bed nucleus of stria terminalis neurons to compare the two scenarios. The inward rectifying Kir current ( IKir) and the hyperpolarization-activated cation current ( Ih) were found to be considerably more effective in regulating the firing under synaptic inputs than under static stimuli. This prediction was experimentally confirmed by dynamic-clamp insertion of a synthetic inwardly rectifying Kir current into the biological neurons. At the same time, ionic currents that activate with depolarization were more effective regulating the firing under static inputs. When two intrinsic currents are concurrently altered such as those under homeostatic regulation, the effects in firing responses under static vs. dynamic inputs can be even more contrasting. Our results show that plastic or homeostatic changes of intrinsic membrane currents can shape the current step responses of neurons and their firing under synaptic inputs in a differential manner.

scholarly journals SnapHiC: a computational pipeline to map chromatin contacts from single cell Hi-C data

2020 ◽  
Author(s):  
Miao Yu ◽  
Armen Abnousi ◽  
Yanxiao Zhang ◽  
Guoqiang Li ◽  
Lindsay Lee ◽  
...  
Keyword(s):  
High Resolution ◽  
Single Cell ◽  
Target Genes ◽  
Embryonic Stem ◽  
Cell Type ◽  
Cortical Cells ◽  
Chromatin Loops ◽  
Chromatin Architecture ◽  
Prefrontal Cortical ◽  
Cell Type Specific

Single cell Hi-C (scHi-C) analysis has been increasingly used to map the chromatin architecture in diverse tissue contexts, but computational tools to define chromatin contacts at high resolution from scHi-C data are still lacking. Here, we describe SnapHiC, a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. We benchmark SnapHiC against HiCCUPS, a common tool for mapping chromatin contacts in bulk Hi-C data, using scHi-C data from 742 mouse embryonic stem cells. We further demonstrate its utility by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells. We uncover cell-type-specific chromatin loops and predict putative target genes for non-coding sequence variants associated with neuropsychiatric disorders. Our results suggest that SnapHiC could facilitate the analysis of cell-type-specific chromatin architecture and gene regulatory programs in complex tissues.

scholarly journals Detection of cell-type-specific risk-CpG sites in epigenome-wide association studies

2018 ◽  
Author(s):  
Xiangyu Luo ◽  
Can Yang ◽  
Yingying Wei
Keyword(s):  
High Resolution ◽  
Statistical Method ◽  
Individual Cell ◽  
Association Studies ◽  
Cell Types ◽  
Cell Type ◽  
Cpg Sites ◽  
Cpg Site ◽  
Cell Type Specific ◽  
Different Cell Types

In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. The current approaches to the association detection only claim whether a cytosine-phosphate-guanine (CpG) site is associated with the phenotype or not, but they cannot determine the cell type in which the risk-CpG site is affected by the phenotype. Here, we propose a solid statistical method, HIgh REsolution (HIRE), which not only substantially improves the power of association detection at the aggregated level as compared to the existing methods but also enables the detection of risk-CpG sites for individual cell types.

Cell-type diversity in the bed nucleus of the stria terminalis to regulate motivated behaviors

2021 ◽  
pp. 113401
Author(s):  
Maria M. Ortiz-Juza ◽  
Rizk A. Alghorazi ◽  
Jose Rodriguez-Romaguera
Keyword(s):  
Stria Terminalis ◽  
Cell Type ◽  
Bed Nucleus ◽  
Motivated Behaviors
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