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 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 All-optical imaging and patterned stimulation with a one-photon endoscope

2021 ◽  
Author(s):  
Jinyong Zhang ◽  
Ryan N Hughes ◽  
Namsoo Kim ◽  
Isabella P Fallon ◽  
Konstantin I bakhurin ◽  
...  
Keyword(s):  
Neural Activity ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Integrated System ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Cellular Resolution ◽  
All Optical ◽  
Freely Moving

While in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation with near cellular resolution (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this highly portable system in freely moving mice, we were able to image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice in the field of view, or to synthesize arbitrary spatiotemporal patterns of photo-stimulation. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for interrogation of neural circuit function in freely moving animals.

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 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 All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0194947 ◽  
Author(s):  
Soon Keen Cheong ◽  
Jennifer M. Strazzeri ◽  
David R. Williams ◽  
William H. Merigan
Keyword(s):  
Retinal Degeneration ◽  
Optical Recording ◽  
Retinal Neurons ◽  
All Optical ◽  
Stimulation Of

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 Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

2015 ◽  
Vol 112 (45) ◽  
pp. 14072-14077 ◽  
Author(s):  
Robert Egger ◽  
Arno C. Schmitt ◽  
Damian J. Wallace ◽  
Bert Sakmann ◽  
Marcel Oberlaender ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Cell Types ◽  
Cortical Layer ◽  
Evoked Responses ◽  
Apical Tuft ◽  
Sensory Evoked ◽  
Pharmacological Manipulations

Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.

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