scholarly journals Temporal regulation of motor behavior on a modified forelimb dexterity test in mice

2020 ◽  
Author(s):  
Hisham Mohammed ◽  
Yue Li ◽  
Paola Di Grazia ◽  
Amanda Bernstein ◽  
Sydney Agger ◽  
...  
Keyword(s):  
Task Difficulty ◽  
Neural Circuit ◽  
Motor Behavior ◽  
High Variability ◽  
Cortical Inhibition ◽  
Significant Percentage ◽  
Temporal Regulation ◽  
Single Pellet ◽  
Circuit Function ◽  
Task Acquisition

ABSTRACTHand and arm manual dexterity is a hallmark of humans and non-human primates. While rodents are less dexterous than primates, they provide powerful models for testing neural circuit function in behavioral output, including dexterous behaviors. In rodents, the single pellet reach task has been used extensively to study both dexterous forelimb motor learning as well as recovery from injury; however, mice exhibit high variability in task acquisition in comparison to rats and a significant percentage fail to learn the task. We have created a recessed version of the task that requires greater dexterity. This subtle modification increases both task difficulty as well as the proportion of mice that show an improvement with training. Furthermore, motor cortex inactivation shows a greater effect on the execution of the recessed forelimb reach task, with distinct effects on reach targeting vs grasping components depending on the timing of inhibitory activation. Kinematic analysis revealed differences in reach targeting upon transient cortical inhibition prior to reach onset. In summary, the recessed single pellet reach task provides a robust assessment of forelimb dexterity in mice and a tool for studying skilled motor acquisition and execution.

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 Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

2019 ◽  
Author(s):  
Manxiu Ma ◽  
Alexandro D. Ramirez ◽  
Tong Wang ◽  
Rachel L. Roberts ◽  
Katherine E. Harmon ◽  
...  
Keyword(s):  
Animal Model ◽  
Light Adaptation ◽  
Neural Circuit ◽  
Oculomotor System ◽  
Gaze Stabilization ◽  
Ocular Disorders ◽  
Motor Apraxia ◽  
Premotor Pathways ◽  
And Function ◽  
Circuit Function

AbstractDown Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

scholarly journals Quantitative synapse analysis for cell-type specific connectomics

2018 ◽  
Author(s):  
Dika A. Kuljis ◽  
Khaled Zemoura ◽  
Cheryl A. Telmer ◽  
Jiseok Lee ◽  
Eunsol Park ◽  
...  
Keyword(s):  
Large Scale ◽  
Neural Circuit ◽  
Apical Dendrite ◽  
Automated Detection ◽  
Cell Type ◽  
Disease States ◽  
Specific Localization ◽  
Cell Type Specific ◽  
Dendritic Branches ◽  
Circuit Function

AbstractAnatomical methods for determining cell-type specific connectivity are essential to inspire and constrain our understanding of neural circuit function. We developed new genetically-encoded reagents for fluorescence-synapse labeling and connectivity analysis in brain tissue, using a fluorogen-activating protein (FAP)-or YFP-coupled, postsynaptically-localized neuroligin-1 targeting sequence (FAP/YFPpost). Sparse viral expression of FAP/YFPpost with the cell-filling, red fluorophore dTomato (dTom) enabled high-throughput, compartment-specific localization of synapses across diverse neuron types in mouse somatosensory cortex. High-resolution confocal image stacks of virally-transduced neurons were used for 3D reconstructions of postsynaptic cells and automated detection of synaptic puncta. We took advantage of the bright, far-red emission of FAPpost puncta for multichannel fluorescence alignment of dendrites, synapses, and presynaptic neurites to assess subtype-specific inhibitory connectivity onto L2 neocortical pyramidal (Pyr) neurons. Quantitative and compartment-specific comparisons show that PV inputs are the dominant source of inhibition at both the soma and across all dendritic branches examined and were particularly concentrated at the primary apical dendrite, a previously unrecognized compartment of L2 Pyr neurons. Our fluorescence-based synapse labeling reagents will facilitate large-scale and cell-type specific quantitation of changes in synaptic connectivity across development, learning, and disease states.

Behavioral and Neurobiological Mechanisms of Pavlovian and Instrumental Extinction Learning

2020 ◽  
Author(s):  
Mark E. Bouton ◽  
Stephen Maren ◽  
Gavan P McNally
Keyword(s):  
Neural Circuit ◽  
Original Learning ◽  
Cortical Inhibition ◽  
Extinction Learning ◽  
Fully Integrated ◽  
Operant Responding ◽  
Prefrontal Cortical ◽  
Pavlovian Extinction ◽  
Inhibitory Learning ◽  
Operant Extinction

This article reviews the behavioral neuroscience of extinction, the phenomenon in which a behavior that has been acquired through Pavlovian or instrumental (operant) learning decreases in strength when the outcome that reinforced it is removed. Behavioral research indicates that neither Pavlovian nor operant extinction depends substantially on erasure of the original learning, but instead depends on new inhibitory learning that is primarily expressed in the context in which it is learned, as exemplified by the renewal effect. Although the nature of the inhibition may differ in Pavlovian and operant extinction, in either case the decline in responding may depend on both generalization decrement and the correction of prediction error. At the neural level, Pavlovian extinction requires a tripartite neural circuit involving the amygdala, prefrontal cortex, and hippocampus. Synaptic plasticity in the amygdala is essential for extinction learning, and prefrontal cortical inhibition of amygdala neurons encoding fear memories is involved in fear retrieval. Hippocampal-prefrontal circuits mediate fear relapse phenomena, including renewal. Instrumental extinction involves distinct ensembles in corticostriatal, striatopallidal, and striatohypothalamic circuits as well as their thalamic returns for inhibitory (extinction) and excitatory (renewal and other relapse phenomena) control over operant responding. The field has made significant progress in recent decades, although a fully integrated biobehavioral understanding still awaits.

scholarly journals Rapid and sustained homeostatic control of presynaptic exocytosis at a central synapse

2019 ◽  
Vol 116 (47) ◽  
pp. 23783-23789 ◽  
Author(s):  
Igor Delvendahl ◽  
Katarzyna Kita ◽  
Martin Müller
Keyword(s):  
Time Scales ◽  
Neural Circuit ◽  
Mossy Fiber ◽  
Pool Size ◽  
Homeostatic Plasticity ◽  
Experimental Conditions ◽  
Central Synapse ◽  
Circuit Function ◽  
Vesicle Pool ◽  
Activity Dependent

Animal behavior is remarkably robust despite constant changes in neural activity. Homeostatic plasticity stabilizes central nervous system (CNS) function on time scales of hours to days. If and how CNS function is stabilized on more rapid time scales remains unknown. Here, we discovered that mossy fiber synapses in the mouse cerebellum homeostatically control synaptic efficacy within minutes after pharmacological glutamate receptor impairment. This rapid form of homeostatic plasticity is expressed presynaptically. We show that modulations of readily releasable vesicle pool size and release probability normalize synaptic strength in a hierarchical fashion upon acute pharmacological and prolonged genetic receptor perturbation. Presynaptic membrane capacitance measurements directly demonstrate regulation of vesicle pool size upon receptor impairment. Moreover, presynaptic voltage-clamp analysis revealed increased Ca2+-current density under specific experimental conditions. Thus, homeostatic modulation of presynaptic exocytosis through specific mechanisms stabilizes synaptic transmission in a CNS circuit on time scales ranging from minutes to months. Rapid presynaptic homeostatic plasticity may ensure stable neural circuit function in light of rapid activity-dependent plasticity.

Optogenetic Dissection of Neural Circuit Function in Behaving Animals

2014 ◽  
pp. 143-160
Author(s):  
Carolina Gutierrez Herrera ◽  
Antoine Adamantidis ◽  
Feng Zhang ◽  
Karl Deisseroth ◽  
Luis de Lecea
Keyword(s):  
Neural Circuit ◽  
Circuit Function

scholarly journals Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

2016 ◽  
Vol 216 (1) ◽  
pp. 231-246 ◽  
Author(s):  
Joseph J. Bruckner ◽  
Hong Zhan ◽  
Scott J. Gratz ◽  
Monica Rao ◽  
Fiona Ukken ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Motor Behavior ◽  
Molecular Organization ◽  
Electrophysiological Studies ◽  
Circuit Function ◽  
Synaptic Vesicle Release ◽  
Ca2 Channels

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

scholarly journals The dialectic of Hebb and homeostasis

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160258 ◽  
Author(s):  
Gina G. Turrigiano
Keyword(s):  
Recent Progress ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Homeostatic Plasticity ◽  
Homeostatic Control ◽  
Spatial And Temporal Scales ◽  
Network Function ◽  
Hebbian Plasticity ◽  
Circuit Function ◽  
Hebbian Mechanisms

It has become widely accepted that homeostatic and Hebbian plasticity mechanisms work hand in glove to refine neural circuit function. Nonetheless, our understanding of how these fundamentally distinct forms of plasticity compliment (and under some circumstances interfere with) each other remains rudimentary. Here, I describe some of the recent progress of the field, as well as some of the deep puzzles that remain. These include unravelling the spatial and temporal scales of different homeostatic and Hebbian mechanisms, determining which aspects of network function are under homeostatic control, and understanding when and how homeostatic and Hebbian mechanisms must be segregated within neural circuits to prevent interference. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

scholarly journals Neural architecture: from cells to circuits

2018 ◽  
Vol 120 (2) ◽  
pp. 854-866 ◽  
Author(s):  
Sarah E. V. Richards ◽  
Stephen D. Van Hooser
Keyword(s):  
Nervous System ◽  
Cerebral Cortex ◽  
Structure Function ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neuronal Morphology ◽  
Neural Architecture ◽  
Synaptic Interactions ◽  
Branching Patterns ◽  
Circuit Function

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.

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