Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits

Ashaber, Mária; Tomina, Yusuke; Kassraian, Pegah; Bushong, Eric A.; Kristan, William B.; Ellisman, Mark H.; Wagenaar, Daniel A.

doi:10.7554/elife.61881

Cited by 10 publications

(6 citation statements)

References 79 publications

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“…A systematic survey of functional connectivity upon single neuron optogenetic stimulation revealed extensive discrepancies between anatomic chemical synaptic wiring and functional connectivity throughout the C. elegans nervous system 80,81 . A partial correlation between anatomic wiring and correlated neuronal activity patterns has been similarly noted in other systems [82][83][84][85] .…”

Section: Discrepancies Between Anatomic and Functional Connectivitysupporting

confidence: 60%

A tonically active master neuron modulates mutually exclusive motor states at two timescales

Meng

Ahamed

et al. 2022

Preprint

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Mutually exclusive behaviors in animals are often driven by independent motor subcircuits that directly or indirectly inhibit each other. For example, in the nematode C. elegans, motor circuits for forward and backward locomotion are gated by premotor interneurons AVB and AVA respectively, which are thought to be connected via reciprocal inhibition. In this study, we dissect the interactions between forward and motor subcircuits in C. elegans by genetic manipulation of AVA's activity via cell-specific characterization of a two-pore potassium channel (TWK-40). AVA has an unusually depolarized resting membrane potential (RMP). Perturbations to its RMP through AVA-specific TWK-40 loss-of-function and AVA-specific TWK-40 gain-of-function, led to dramatic changes in both forward and backward motor activity. AVA, thus regulated both backward and forward locomotion in C. elegans, functioning as a master neuron for overall locomotion. These effects required chemical transmission from AVA and were dependent on AVB neurons. We were able to reconcile results of genetic perturbation with optogenetic manipulation by carefully designed stimulation protocols. Finding that phasic optogenetic activation of AVA leads to backward locomotion, while tonic optogenetic activation potentiates forward locomotion. These results propose that a single neuron can regulate the activity of motor circuits generating two mutually exclusive behaviors.

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Section: Discrepancies Between Anatomic and Functional Connectivitysupporting

confidence: 60%

A tonically active master neuron modulates mutually exclusive motor states at two timescales

Meng

Ahamed

et al. 2022

Preprint

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“…While synaptic clustering appears to be near-ubiquitous across brain areas and species ( ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ), there is striking variability in the qualitative characteristics of clusters. The receptive field of a synapse – the sensory feature encoded by the synaptic input – can be used to describe the properties of clusters.…”

Section: Organization Of Excitatory Synapsesmentioning

confidence: 99%

Emergence of synaptic organization and computation in dendrites

Kirchner

Gjorgjieva

2021

Neuroforum

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Single neurons in the brain exhibit astounding computational capabilities, which gradually emerge throughout development and enable them to become integrated into complex neural circuits. These capabilities derive in part from the precise arrangement of synaptic inputs on the neurons’ dendrites. While the full computational benefits of this arrangement are still unknown, a picture emerges in which synapses organize according to their functional properties across multiple spatial scales. In particular, on the local scale (tens of microns), excitatory synaptic inputs tend to form clusters according to their functional similarity, whereas on the scale of individual dendrites or the entire tree, synaptic inputs exhibit dendritic maps where excitatory synapse function varies smoothly with location on the tree. The development of this organization is supported by inhibitory synapses, which are carefully interleaved with excitatory synapses and can flexibly modulate activity and plasticity of excitatory synapses. Here, we summarize recent experimental and theoretical research on the developmental emergence of this synaptic organization and its impact on neural computations.

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“…Sample preparation protocol for correlative microscopy was adapted from Ashaber et al 37 . Cells were washed with 0.2 M sodium cacodylate buffer and fixed using Karnovsky’s fixative (2% paraformaldehyde, 2.5% glutaraldehyde in 0.15 M cacodylate buffer containing 2 mM CaCl 2 ) for overnight at +4 C followed by three sequential washes with ddH 2 O.…”

Section: Methodsmentioning

confidence: 99%

Live cell imaging and CLEM reveals effects of Mutant Huntingtin Aggregation Process

Yiğit

Aydın

Kurnaz

et al. 2023

Preprint

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Huntington's disease is a neurodegenerative disease caused by expansion of CAG repeats in exon-1 of Huntingtin (HTT) gene leading to production of mutant Huntingtin (mHtt) protein. Htt protein is known to play crucial roles in regulation of cytoskeletal dynamics and vesicular transport in physiological conditions. By combining in vitro time-lapse imaging and correlative light and electron microscopy (CLEM), we investigated the subcellular dynamics of mHtt during the process aggregate formation. Here we show that distribution of F-actin is affected by mHtt aggregation. F-actin tends to relocate from the peripheral to perinuclear area in cells with mHtt aggregates, possibly caused by sequestration of F-actin from cell membrane to aggregation zones. In accordance with this, mHtt in hippocampal neurons were aggregated into axonal varicosities together with F-actin as they have higher F-actin expression in their neurites compared to their soma. Additionally, correlative light and electron microscopy (CLEM) revealed increased mitochondrial accumulation at the periphery of mHtt aggregates which is surrounded by a F-actin mesh. Mitochondria targeted HyPerRed, a genetically encoded hydrogen peroxide sensor, revealed that oxidative stress in mHtt expressing cells increased. Thus, our findings give new insights about the pathology caused by mHtt through interplay of aggregates with F-actin cytoskeleton and mitochondrial oxidative stress.

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Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits

Cited by 10 publications

References 79 publications

A tonically active master neuron modulates mutually exclusive motor states at two timescales

A tonically active master neuron modulates mutually exclusive motor states at two timescales

Emergence of synaptic organization and computation in dendrites

Live cell imaging and CLEM reveals effects of Mutant Huntingtin Aggregation Process

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