scholarly journals Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Cian O'Donnell ◽  
J Tiago Gonçalves ◽  
Carlos Portera-Cailliau ◽  
Terrence J Sejnowski
Keyword(s):  
Neural Circuit ◽  
Fragile X ◽  
Brain Disorders ◽  
Imaging Data ◽  
Neural Firing ◽  
Knock Out ◽  
Brain Circuitry ◽  
Circuit Function ◽  
Cellular Components

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.

scholarly journals Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

2016 ◽  
Author(s):  
Cian O’Donnell ◽  
J. Tiago Gonçalves ◽  
Carlos Portera-Cailliau ◽  
Terrence J. Sejnowski
Keyword(s):  
Neural Circuit ◽  
Fragile X ◽  
Brain Disorders ◽  
Imaging Data ◽  
Neural Firing ◽  
Knock Out ◽  
Brain Circuitry ◽  
Circuit Function ◽  
Cellular Components

AbstractA leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this onedimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here we combined computational simulations with analysis of in vivo 2-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: 1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; 2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; 3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher-dimensional models that can better capture the multidimensional computational functions of neural circuits.

scholarly journals Neural circuit function redundancy in brain disorders

2021 ◽  
Vol 70 ◽  
pp. 74-80
Author(s):  
Beatriz E.P. Mizusaki ◽  
Cian O'Donnell
Keyword(s):  
Neural Circuit ◽  
Brain Disorders ◽  
Circuit Function

scholarly journals All-optical interrogation of neural circuits in behaving mice

2021 ◽  
Author(s):  
Lloyd E. Russell ◽  
Henry W.P. Dalgleish ◽  
Rebecca Nutbrown ◽  
Oliver Gauld ◽  
Dustin Herrmann ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Barrel Cortex ◽  
Brain Area ◽  
Imaging Data ◽  
Temporal Precision ◽  
Two Photon ◽  
All Optical ◽  
The Impact

Recent advances combining two-photon calcium imaging and two-photon optogenetics with digital holography now allow us to read and write neural activity in vivo at cellular resolution with millisecond temporal precision. Such 'all-optical' techniques enable experimenters to probe the impact of functionally defined neurons on neural circuit function and behavioural output with new levels of precision. This protocol describes the experimental strategy and workflow for successful completion of typical all-optical interrogation experiments in awake, behaving head-fixed mice. We describe modular procedures for the setup and calibration of an all-optical system, the preparation of an indicator and opsin-expressing and task-performing animal, the characterization of functional and photostimulation responses and the design and implementation of an all-optical experiment. We discuss optimizations for efficiently selecting and targeting neuronal ensembles for photostimulation sequences, as well as generating photostimulation response maps from the imaging data that can be used to examine the impact of photostimulation on the local circuit. We demonstrate the utility of this strategy using all-optical experiments in three different brain areas - barrel cortex, visual cortex and hippocampus - using different experimental setups. This approach can in principle be adapted to any brain area for all-optical interrogation experiments to probe functional connectivity in neural circuits and for investigating the relationship between neural circuit activity and behaviour.

scholarly journals BACE inhibition-dependent repair of Alzheimer’s pathophysiology

2017 ◽  
Vol 114 (32) ◽  
pp. 8631-8636 ◽  
Author(s):  
Aylin D. Keskin ◽  
Maja Kekuš ◽  
Helmuth Adelsberger ◽  
Ulf Neumann ◽  
Derya R. Shimshek ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Cognitive Impairments ◽  
Amyloid Β ◽  
Pathogenic Role ◽  
Memory Impairments ◽  
Wide Range ◽  
Key Enzyme ◽  
Potential Benefits ◽  
Circuit Function

Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.

Oxytocin, Neural Plasticity, and Social Behavior

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Robert C. Froemke ◽  
Larry J. Young
Keyword(s):  
Social Behavior ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Social Behaviors ◽  
Neuron Activity ◽  
Annual Review ◽  
Publication Date ◽  
Social Stimuli ◽  
Circuit Function

Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo. These studies indicate that oxytocin can enhance the salience of social stimuli and increase signal-to-noise ratios by modulating spiking and synaptic plasticity in the context of circuits and networks. We highlight oxytocin effects on social behavior in nontraditional organisms such as prairie voles and discuss opportunities to enhance the utility of these organisms for studying circuit-level modulation of social behaviors. We then discuss recent insights into oxytocin neuron activity during social interactions. We conclude by discussing some of the major questions and opportunities in the field ahead. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Store-independent modulation of Ca2+ entry through Orai by Septin 7

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Bipan Kumar Deb ◽  
Trayambak Pathak ◽  
Gaiti Hasan
Keyword(s):  
Neural Circuit ◽  
Cell Types ◽  
Negative Regulator ◽  
Flight Duration ◽  
Multiple Cell ◽  
Circuit Function ◽  
Trisphosphate Receptor ◽  
Molecular Brake ◽  
Orai Channels

Abstract Orai channels are required for store-operated Ca2+ entry (SOCE) in multiple cell types. Septins are a class of GTP-binding proteins that function as diffusion barriers in cells. Here we show that Septin 7 acts as a ‘molecular brake’ on activation of Orai channels in Drosophila neurons. Lowering Septin 7 levels results in dOrai-mediated Ca2+ entry and higher cytosolic Ca2+ in resting neurons. This Ca2+ entry is independent of depletion of endoplasmic reticulum Ca2+ stores and Ca2+ release through the inositol-1,4,5-trisphosphate receptor. Importantly, store-independent Ca2+ entry through Orai compensates for reduced SOCE in the Drosophila flight circuit. Moreover, overexpression of Septin 7 reduces both SOCE and flight duration, supporting its role as a negative regulator of Orai channel function in vivo. Septin 7 levels in neurons can, therefore, alter neural circuit function by modulating Orai function and Ca2+ homeostasis.

scholarly journals A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types

2019 ◽  
Author(s):  
Donghoon Lee ◽  
Maiko Kume ◽  
Timothy E Holy
Keyword(s):  
Neural Circuit ◽  
Strong Predictor ◽  
Ectopic Expression ◽  
Cell Types ◽  
Specific Cell ◽  
Molecular Logic ◽  
Neuronal Types ◽  
A Cell ◽  
Circuit Function

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. Here, we report physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression-profiling cells based on their functional properties. We demonstrate that PhOTseq is capable of selecting rare cell types and enriching them by nearly one hundred-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among vomeronasal pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands, and revealed that the primary sequence of a chemoreceptor was an unexpectedly strong predictor of functional similarity.

scholarly journals All-optical electrophysiology reveals excitation, inhibition, and neuromodulation in cortical layer 1

2019 ◽  
Author(s):  
Linlin Z. Fan ◽  
Simon Kheifets ◽  
Urs L. Böhm ◽  
Kiryl D. Piatkevich ◽  
Hao Wu ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Barrel Cortex ◽  
Cortical Layer ◽  
Optical Recording ◽  
Tight Coupling ◽  
Basic Principles ◽  
All Optical ◽  
The Stability ◽  
Circuit Function

AbstractThe stability of neural dynamics arises through a tight coupling of excitatory (E) and inhibitory (I) signals. Genetically encoded voltage indicators (GEVIs) can report both spikes and subthreshold dynamics in vivo, but voltage only reveals the combined effects of E and I synaptic inputs, not their separate contributions individually. Here we combine optical recording of membrane voltage with simultaneous optogenetic manipulation to probe E and I individually in barrel cortex Layer 1 (L1) neurons in awake mice. Our studies reveal how the L1 microcircuit integrates thalamocortical excitation, lateral inhibition and top-down neuromodulatory inputs. We develop a simple computational model of the L1 microcircuit which captures the main features of our data. Together, these results suggest a model for computation in L1 interneurons consistent with their hypothesized role in attentional gating of the underlying cortex. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo.One Sentence SummaryAll-optical electrophysiology revealed the function in awake mice of an inhibitory microcircuit in barrel cortex Layer 1.

scholarly journals ICoRD: Iterative Correlation-Based ROI Detection Method for the Extraction of Neural Signals in Calcium Imaging

2021 ◽  
Author(s):  
Seongtak Kang ◽  
Jiho Park ◽  
Kyungsoo Kim ◽  
Sung-Ho Lim ◽  
Joon Ho Choi ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Neural Circuit ◽  
Detection Methods ◽  
Calcium Signal ◽  
Noise Power ◽  
Imaging Data ◽  
Calcium Signals ◽  
Low Snr ◽  
Target Neuron

In vivo calcium imaging is a standard neuroimaging technique that allows the simultaneous observation of neuronal population activity. In calcium imaging, the activation signals of neurons are key information for the investigation of neural circuits. For efficient extraction of the calcium signals of neurons, selective detection of the region of interest (ROI) pixels corresponding to the active subcellular region of the target neuron is essential. However, current ROI detection methods for calcium imaging data exhibit relatively low extraction performance from neurons with a low signal-to-noise power ratio (SNR). This is problematic because a low SNR is unavoidable in many biological experimental settings. Therefore, we propose an iterative correlation-based ROI detection (ICoRD) method that robustly extracts the calcium signal of the target neuron from a calcium imaging series with severe noise. ICoRD extracts calcium signals closer to the ground truth than the conventional method from simulated calcium imaging data in all low SNR ranges. Additionally, this study confirmed that ICoRD robustly extracts activation signals against noise, even within in vivo environments. ICoRD showed reliable detection from neurons with low SNR and sparse activation, which were not detected by the conventional methods. ICoRD will facilitate our understanding of neural circuit activity by providing significantly improved ROI detection from noisy images.

scholarly journals δ-Catenin engages the autophagy pathway to sculpt the developing dendritic arbor

2020 ◽  
Vol 295 (32) ◽  
pp. 10988-11001
Author(s):  
Cheryl Ligon ◽  
Eunju Seong ◽  
Ethan J. Schroeder ◽  
Nicholas W. DeKorver ◽  
Li Yuan ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Neural Circuit ◽  
Time Lapse ◽  
Apical Dendrite ◽  
Dendritic Arbor ◽  
Autophagy Pathway ◽  
Circuit Function ◽  
Time Lapse Imaging ◽  
Cellular Components ◽  
Adhesion Complex

The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which δ-catenin, a component of the cadherin–catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development. Loss or knockdown of δ-catenin uncoupled this coordination, leading to retraction of the apical dendrite without altering basolateral dendrite dynamics. Autophagy is a key cellular pathway that allows degradation of cellular components. We observed that the impairment of the dendritic arbor resulting from δ-catenin knockdown could be reversed by knockdown of autophagy-related 7 (ATG7), a component of the autophagy machinery. We propose that δ-catenin regulates the dendritic arbor by coordinating the dynamics of individual dendrites and that the autophagy mechanism may be leveraged by δ-catenin and other effectors to sculpt the developing dendritic arbor. Our findings have implications for the management of neurological disorders, such as autism and intellectual disability, that are characterized by dendritic aberrations.

Sign in / Sign up

Export Citation Format

Share Document