Optimal synaptic dynamics for memory maintenance in the presence of noise

Mapping Intimacies ◽

10.1101/2020.08.19.257220 ◽

2020 ◽

Author(s):

Dhruva V Raman ◽

Timothy O’Leary

Keyword(s):

Neural Circuit ◽

Behavioural Change ◽

Experimental Measurements ◽

Synaptic Connections ◽

Biological Noise ◽

Brain Areas ◽

Dependent Component ◽

Synaptic Dynamics ◽

Circuit Function ◽

Activity Dependent

ABSTRACTSynaptic connections in many brain areas have been found to fluctuate significantly, with substantial turnover and remodelling occurring over hours to days. Remarkably, this flux in connectivity persists in the absence of overt learning or behavioural change. What proportion of these ongoing fluctuations can be attributed to systematic plasticity processes that maintain memories and neural circuit function? We show under general conditions that the optimal magnitude of systematic plasticity is typically less than the magnitude of perturbations due to internal biological noise. Thus, for any given amount of unavoidable noise, 50% or more of total synaptic turnover should be effectively random for optimal memory maintenance. Our analysis does not depend on specific neural circuit architectures or plasticity mechanisms and predicts previously unexplained experimental measurements of the activity-dependent component of ongoing plasticity.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909675116 ◽

2019 ◽

Vol 116 (47) ◽

pp. 23783-23789 ◽

Cited By ~ 6

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.

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Trans-Synaptic Spread of Amyloid-βin Alzheimer’s Disease: Paths toβ-Amyloidosis

Neural Plasticity ◽

10.1155/2017/5281829 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Annabella Pignataro ◽

Silvia Middei

Keyword(s):

Neuronal Activity ◽

Amyloid Plaques ◽

Brain Regions ◽

Amyloid Peptide ◽

Synaptic Connections ◽

Brain Areas ◽

Close Link ◽

Gradual Accumulation ◽

Cortical Regions ◽

Activity Dependent

Neuronal activity has a strong causal role in the production and release of the neurotoxicβ-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβinto amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between Aβand activity is not always linear and recent studies report exceptions to the view of “more activity, more plaques.” Here, we review the literature about the activity-dependent production of Aβin both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to Aβaccumulation. Next, we will examine data supporting the hypothesis that, since Aβis released from synaptic terminals,β-amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to Aβaccumulation. Finally, we consider possible mechanisms that account forβ-amyloidosis progression through synaptically linked regions.

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Compensatory variability in network parameters enhances memory performance in the Drosophila mushroom body

10.1101/2021.02.03.429444 ◽

2021 ◽

Author(s):

Nada Y. Abdelrahman ◽

Eleni Vasilaki ◽

Andrew C. Lin

Keyword(s):

Mushroom Body ◽

Neural Circuit ◽

Memory Performance ◽

Activity Levels ◽

Compensatory Mechanisms ◽

Network Parameters ◽

Kenyon Cells ◽

Average Activity ◽

Circuit Function ◽

Activity Dependent

AbstractNeural circuits use homeostatic compensation to achieve consistent behaviour despite variability in underlying intrinsic and network parameters. However, it remains unclear how compensation regulates variability across a population of the same type of neurons within an individual, and what computational benefits might result from such compensation. We address these questions in the Drosophila mushroom body, the fly’s olfactory memory center. In a computational model, we show that memory performance is degraded when the mushroom body’s principal neurons, Kenyon cells (KCs), vary realistically in key parameters governing their excitability, because the resulting inter-KC variability in average activity levels makes odor representations less separable. However, memory performance is rescued while maintaining realistic variability if parameters compensate for each other to equalize KC average activity. Such compensation can be achieved through both activity-dependent and activity-independent mechanisms. Finally, we show that correlations predicted by our model’s compensatory mechanisms appear in the Drosophila hemibrain connectome. These findings reveal compensatory variability in the mushroom body and describe its computational benefits for associative memory.Significance statementHow does variability between neurons affect neural circuit function? How might neurons behave similarly despite having different underlying features? We addressed these questions in neurons called Kenyon cells, which store olfactory memories in flies. Kenyon cells differ among themselves in key features that affect how active they are, and in a model of the fly’s memory circuit, adding this inter-neuronal variability made the model fly worse at learning the values of multiple odors. However, memory performance was rescued if compensation between the variable underlying features allowed Kenyon cells to be equally active on average, and we found the hypothesized compensatory variability in real Kenyon cells’ anatomy. This work reveals the existence and computational benefits of compensatory variability in neural networks.

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Myelin Plasticity and Nervous System Function

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-080317-061853 ◽

2018 ◽

Vol 41 (1) ◽

pp. 61-76 ◽

Cited By ~ 42

Author(s):

Michelle Monje

Keyword(s):

Nervous System ◽

Neural Circuit ◽

Neurological Function ◽

Nervous System Activity ◽

Second Mode ◽

Nervous System Function ◽

Plastic Changes ◽

Circuit Function ◽

Activity Dependent ◽

Development Proceeds

Structural plasticity in the myelinated infrastructure of the nervous system has come to light. Although an innate program of myelin development proceeds independent of nervous system activity, a second mode of myelination exists in which activity-dependent, plastic changes in myelin-forming cells influence myelin structure and neurological function. These complementary and possibly temporally overlapping activity-independent and activity-dependent modes of myelination crystallize in a model of experience-modulated myelin development and plasticity with broad implications for neurological function. In this article, I consider the contributions of myelin to neural circuit function, the dynamic influences of experience on myelin microstructure, and the role that plasticity of myelin may play in cognition.

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Rapid and Sustained Homeostatic Control of Presynaptic Exocytosis at a Central Synapse

10.1101/785535 ◽

2019 ◽

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

AbstractAnimal 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 calcium-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.

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Neural circuit function redundancy in brain disorders

Current Opinion in Neurobiology ◽

10.1016/j.conb.2021.07.008 ◽

2021 ◽

Vol 70 ◽

pp. 74-80

Author(s):

Beatriz E.P. Mizusaki ◽

Cian O'Donnell

Keyword(s):

Neural Circuit ◽

Brain Disorders ◽

Circuit Function

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

10.1101/658161 ◽

2019 ◽

Cited By ~ 2

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.

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Quantitative synapse analysis for cell-type specific connectomics

10.1101/386912 ◽

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.

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