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Dendritic Spikes Expand the Range of Well Tolerated Population Noise Structures.

ABSTRACT: The brain operates surprisingly well despite the noisy nature of individual neurons. The central mechanism for noise mitigation in the nervous system is thought to involve averaging over multiple noise-corrupted inputs. Subsequently, there has been considerable interest in identifying noise structures that can be integrated linearly in a way that preserves reliable signal encoding. By analyzing realistic synaptic integration in biophysically accurate neuronal models, I report a complementary denoising approach that is mediated by focal dendritic spikes. Dendritic spikes might seem to be unlikely candidates for noise reduction due to their miniscule integration compartments and poor averaging abilities. Nonetheless, the extra thresholding step introduced by dendritic spike generation increases neuronal tolerance for a broad category of noise structures, some of which cannot be resolved well with averaging. This property of active dendrites compensates for compartment size constraints and expands the repertoire of conditions that can be processed by neuronal populations.SIGNIFICANCE STATEMENT Noise, or random variability, is a prominent feature of the neuronal code and poses a fundamental challenge for information processing. To reconcile the surprisingly accurate output of the brain with the inherent noisiness of biological systems, previous work examined signal integration in idealized neurons. The notion that emerged from this body of work is that accurate signal representation relies largely on input averaging in neuronal dendrites. In contrast to the prevailing view, I show that denoising in simulated neurons with realistic morphology and biophysical properties follows a different strategy: dendritic spikes act as classifiers that assist in extracting information from a variety of noise structures that have been considered before to be particularly disruptive for reliable brain function.

SUBMITTER: Poleg-Polsky A

PROVIDER: S-EPMC6855677 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Dendritic Spikes Expand the Range of Well Tolerated Population Noise Structures.

Poleg-Polsky Alon A

The Journal of neuroscience : the official journal of the Society for Neuroscience 20190926 46

The brain operates surprisingly well despite the noisy nature of individual neurons. The central mechanism for noise mitigation in the nervous system is thought to involve averaging over multiple noise-corrupted inputs. Subsequently, there has been considerable interest in identifying noise structures that can be integrated linearly in a way that preserves reliable signal encoding. By analyzing realistic synaptic integration in biophysically accurate neuronal models, I report a complementary den ...[more]

PMID: 31558617

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Project description:IntroductionDolutegravir (DTG) is recommended as part of first-line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG-based regimens.MethodsThai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG-related AEs and discontinuations were described.ResultsA total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI) <18.5 kg/m2 . Participants were on ART for a median of 124 weeks before switching to DTG. The median (IQR) body weight increased from 63 (56 to 70) kg before to 65 (58 to 73) kg (p < 0.0001) after 48 weeks of DTG. Forty-nine (16%) developed DTG-related AEs, corresponding to an incidence of 16.6 per 100 person-years. Neuropsychiatric symptoms were most frequently encountered (n = 25, 8%), followed by laboratory abnormalities (n = 16, 5%). Six (2%) discontinued DTG, corresponding to an incidence of 2.4 per 100 person-years. All discontinuations were due to increased liver enzymes in the presence of hepatitis C virus coinfection. In the multivariate analysis, incident hepatitis C virus infection was the only risk factor for discontinuing DTG (hazard ratio 59.4, 95% CI 8.5 to 297.9, p < 0.0001). Neither low BMI nor concurrent abacavir therapy was associated with discontinuation.ConclusionsDTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety.

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Dendritic Spikes Expand the Range of Well Tolerated Population Noise Structures.

Publications

Dendritic Spikes Expand the Range of Well Tolerated Population Noise Structures.

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