Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury

Sakurai, Akira; Tamvacakis, Arianna N; Katz, Paul S.

doi:10.7554/elife.02598

Cited by 36 publications

(42 citation statements)

References 102 publications

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“…In either case, brain asymmetry is implicated in psychiatric disorders (49), suggesting that regulation of individual-to-individual variability may have clinical dimensions. Individual variation in wiring (44,45,50), physiology (51), and behavior (19,40) may prove to be a very general feature of neural circuits, with broad implications both for our basic understanding of developmental neurobiology and the emergence of behavioral phenotypes at the individual level.…”

Section: Discussionmentioning

confidence: 99%

Neuronal control of locomotor handedness in Drosophila

Buchanan¹,

Kain²,

Bivort

2015

Proc. Natl. Acad. Sci. U.S.A.

144

184

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Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-toindividual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.behavior | individuality | personality | circuit mapping | central complex H and dominance-better performance using either the left or right hand-is a familiar human trait, moderately heritable (1), and regulated by many genes (2), including those involved in general body symmetry (3). However, behavioral handedness in general, i.e., the preferential performance of a behavior on one side of the body or with a particular chiral twist, is a multifaceted phenomenon. For example, in the absence of visual feedback, people display clockwise or counterclockwise biases in their walking behavior (4). This "locomotor handedness" is uncorrelated to hand dominance or gross morphological asymmetry and instead may be due to asymmetries in the collection and processing of sensory information, resulting in individual locomotor biases with a neurological basis (4, 5).Handed behavioral tendencies specific to individuals are also prevalent throughout the animal kingdom and have been shown in species as disparate as mice (paw use) (6), octopi (eye use) (7), and tortoises (side rolled on during righting) (8). There is also evidence that, at the population mean level, some species of insects have handed behaviors and asymmetric neurophysiological patterns (9). However, there has been little investigation of the differences in handed behaviors among individuals of the same insect species, and the mechanisms by which asymmetries are instilled in behavior are unknown. Considering beha...

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Section: Discussionmentioning

confidence: 99%

Neuronal control of locomotor handedness in Drosophila

Buchanan¹,

Kain²,

Bivort

2015

Proc. Natl. Acad. Sci. U.S.A.

144

184

View full text Add to dashboard Cite

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“…Perhaps this can help the animal avoid analysis paralysis, or perhaps it is a feature of noisy biological systems. Individual variation in wiring 26–28 , physiology 29 and behavior 9,30 may prove to be a very general feature of neural circuits, with broad implications both for our basic understanding of developmental neurobiology and the emergence of behavioral phenotypes at the individual level.…”

mentioning

confidence: 99%

Neuronal control of locomotor handedness in Drosophila

Buchanan¹,

Kain²,

Bivort

2014

Preprint

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Handedness in humans – better performance using either the left or right hand – is personally familiar, moderately heritable1, and regulated by many genes2, including those involved in general body symmetry3. But behavioral handedness, i.e. lateralization, is a multifaceted phenomenon. For example, people display clockwise or counter-clockwise biases in their walking behavior that is uncorrelated to their hand dominance4,5, and lateralized behavioral biases have been shown in species as disparate as mice (paw usage6), octopi (eye usage7), and tortoises (side rolled on during righting8). However, the mechanisms by which asymmetries are instilled in behavior are unknown, and a system for studying behavioral handedness in a genetically tractable model system is needed. Here we show that Drosophila melanogaster flies exhibit striking variability in their left-right choice behavior during locomotion. Very strongly biased "left-handed" and "right-handed" individuals are common in every line assayed. The handedness of an individual persists for its lifetime, but is not passed on to progeny, suggesting that mechanisms other than genetics determine individual handedness. We use the Drosophila transgenic toolkit to map a specific set of neurons within the central complex that regulates the strength of behavioral handedness within a line. These findings give insights into choice behaviors and laterality in a simple model organism, and demonstrate that individuals from isogenic populations reared under experimentally identical conditions nevertheless display idiosyncratic behaviors.

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“…; Sakurai et al . ). We are unaware of any comparable studies directly addressing this issue in somatosensory afferents.…”

Section: Discussionmentioning

confidence: 97%

Using dynamic clamp to quantify pathological changes in the excitability of primary somatosensory neurons

Takkala

Prescott

2018

The Journal of Physiology

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Key points Primary somatosensory neurons normally respond to somatic depolarization with transient spiking but can switch to repetitive spiking under pathological conditions. This switch in spiking pattern reflects a qualitative change in spike initiation dynamics and contributes to the hyperexcitability associated with chronic pain.Neurons can be converted to repetitive spiking by adding a virtual conductance using dynamic clamp. By titrating the conductance to determine how much must be added to cause repetitive spiking, we found that small cells are more susceptible to switching (i.e. required less added conductance) than medium–large cells.By measuring how much less conductance is required to cause repetitive spiking when dynamic clamp was combined with other pathomimetic manipulations (e.g. application of inflammatory mediators), we measured how much each manipulation facilitated repetitive spiking.Our results suggest that many pathological factors facilitate repetitive spiking but that the switch to repetitive spiking requires the cumulative effect of many co‐occurring factors. AbstractPrimary somatosensory neurons become hyperexcitable in many chronic pain conditions. Hyperexcitability can include a switch from transient to repetitive spiking during sustained somatic depolarization. This switch results from diverse pathological processes that impact ion channel expression or function. Because multiple pathological processes co‐occur, isolating how much each contributes to switching the spiking pattern is difficult. Our approach to this challenge involves adding a virtual sodium conductance via dynamic clamp. The magnitude of that conductance was titrated to determine the minimum required to enable rheobasic stimulation to evoke repetitive spiking. The minimum required conductance, termed g¯ Na ∗, was re‐measured before and during manipulations designed to model various pathological processes in vitro. The reduction in g¯ Na ∗ caused by each pathomimetic manipulation reflects how much the modelled process contributes to switching the spiking pattern. We found that elevating extracellular potassium or applying inflammatory mediators reduced g¯ Na ∗ whereas direct hyperpolarization had no effect. Inflammatory mediators reduced g¯ Na ∗ more in medium–large (>30 μm diameter) neurons than in small (⩽30 μm diameter) neurons, but had equivalent effects in cutaneous and muscle afferents. The repetitive spiking induced by dynamic clamp was also found to differ between small and medium–large neurons, thus revealing latent differences in adaptation. Our study demonstrates a novel way to determine to what extent individual pathological factors facilitate repetitive spiking. Our results suggest that most factors facilitate but do not cause repetitive spiking on their own, and, therefore, that a switch to repetitive spiking results from the cumulative effect of many co‐occurring factors.

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Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury

Cited by 36 publications

References 102 publications

Neuronal control of locomotor handedness in Drosophila

Neuronal control of locomotor handedness in Drosophila

Neuronal control of locomotor handedness in Drosophila

Using dynamic clamp to quantify pathological changes in the excitability of primary somatosensory neurons

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