Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods

Nitabach, Michael N.; Wu, Ying; Sheeba, Vasu; Lemon, William C.; Strumbos, John G.; Zelensky, Paul K.; White, Benjamin H.; Holmes, Todd C.

doi:10.1523/jneurosci.3915-05.2006

Cited by 270 publications

(333 citation statements)

References 58 publications

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“…Two transgenic fly lines containing the NaChBac ion channel transgene yw;UAS-NaChBac1 and yw;UAS-NaChBac4 (gifts from Benjamin White, National Institute of Mental Health, Bethesda, MD) were used along with a control line carrying a nonconducting modified Drosophila open rectifier potassium (dORK) channel yw;UASdORK⌬-NC1, which were described previously (Nitabach et al, 2002(Nitabach et al, , 2006. To express these channels in LNv neurons using the UAS-GAL4 system, which allows for targeted expression of a gene of interest (Brand and Perrimon, 1993), they were crossed with yw;pdf-GAL4 (Renn et al, 1999).…”

Section: Methodsmentioning

confidence: 99%

“…Park, University of Tennessee, Nashville, TN); washes with PBS-0.5% Triton X-100, incubation with anti-rabbit Alexa 488 and anti-rat Alexa 633 followed by more washes with PBS-0.5% Triton X-100. Methodology for immunocytochemistry and antibody against PER and PDF are as described previously (Price et al, 1998;Nitabach et al, 2006). For cell-filled samples, a similar procedure was followed with Alexa-555 conjugated Streptavidin incubation for 24 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…We showed previously that targeted expression of a low threshold voltage-gated sodium channel NaChBac, in the LNv results in long-term stable concurrent multiple rhythms of locomotor activity with ϳ60% of flies showing activity consolidated into at least two components in DD (Nitabach et al, 2006). Yet molecular oscillations show circuit-wide short-term desynchrony between the dorsal subgroups DN1 and DN2, compared with the sLNv, and LNd subgroup, when assayed on days 2 and 5 in DD (Nitabach et al, 2006) (supplemental Fig.…”

Section: Altered Electrical Activity Of Lnv Neurons Causes Initial Armentioning

confidence: 99%

“…Based on measurements of molecular oscillations in the different subgroups in pdf 01 null flies (Peng et al, 2003;Lin et al, 2004) and phase shifts in locomotor activity rhythm by peptide injection in the cockroach brain (Petri and Stengl, 1997) it has been postulated that PDF is responsible for the synchrony in molecular oscillations both within and among pacemaker neuronal subgroups. The electrical properties of the pacemaker neurons are critical for normal circadian behavioral and molecular rhythms (Nitabach et al, 2002;Nitabach et al, 2005;Nitabach et al, 2006;de la Paz Fernandez et al, 2007). We have shown previously that targeted expression of a voltage-gated sodium channel (NaChBac) in LNv neurons results in polyrhythmic free-running bouts of locomotor activity under DD that persists for several weeks.…”

Section: Introductionmentioning

confidence: 99%

“…We have shown previously that targeted expression of a voltage-gated sodium channel (NaChBac) in LNv neurons results in polyrhythmic free-running bouts of locomotor activity under DD that persists for several weeks. Furthermore, the underlying molecular oscillations among the different neuronal subgroups were desynchronized after several days in darkness and such effects were likely to be mediated via PDF (Nitabach et al, 2006). To investigate the apparent anomaly of asynchronous molecular oscillation after short-term exposure to constant darkness while rhythmic (albeit, complex) activity persisted under long-term exposure to constant darkness, we conducted a more detailed analysis of the behavioral phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms

Sheeba

Sharma²,

Gu³

et al. 2008

J. Neurosci.

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Circadian pacemaker circuits consist of ensembles of neurons, each expressing molecular oscillations, but how circuit-wide coordination of multiple oscillators regulates rhythmic physiological and behavioral outputs remains an open question. To investigate the relationship between the pattern of oscillator phase throughout the circadian pacemaker circuit and locomotor activity rhythms in Drosophila, we perturbed the electrical activity and pigment dispersing factor (PDF) levels of the lateral ventral neurons (LNv) and assayed their combinatorial effect on molecular oscillations in different parts of the circuit and on locomotor activity behavior. Altered electrical activity of PDF-expressing LNv causes initial behavioral arrhythmicity followed by gradual long-term emergence of two concurrent short-and long-period circadian behavioral activity bouts in ϳ60% of flies. Initial desynchrony of circuit-wide molecular oscillations is followed by the emergence of a novel pattern of period (PER) synchrony whereby two subgroups of dorsal neurons (DN1 and DN2) exhibit PER oscillation peaks coinciding with two activity bouts, whereas other neuronal subgroups exhibit a single PER peak coinciding with one of the two activity bouts. The emergence of this novel pattern of circuit-wide oscillator synchrony is not accompanied by concurrent change in the electrical activity of the LNv. In PDF-null flies, altered electrical activity of LNv drives a short-period circadian activity bout only, indicating that PDF-independent factors underlie the short-period circadian activity component and that the long-period circadian component is PDF-dependent. Thus, polyrhythmic behavioral patterns in electrically manipulated flies are regulated by circuit-wide coordination of molecular oscillations and electrical activity of LNv via PDF-dependent and -independent factors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Altered Electrical Activity Of Lnv Neurons Causes Initial Armentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms

Sheeba

Sharma²,

Gu³

et al. 2008

J. Neurosci.

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The “New Math” of Neuroscience: Genetic Tools for Accessing and Electively Manipulating Neurons

Schoofs

Pankratz

Goulding

2017

Neurobiology of Motor Control

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Gliomatosis cerebri: 20 Years of experience at the Children's Hospital of Philadelphia

Armstrong¹,

Phillips²,

Rorke-Adams³

et al. 2006

Cancer

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BACKGROUND.Gliomatosis cerebri (GC) is a rare and typically fatal glial neoplasm of the central nervous system. In this report, the authors describe the largest cohort of children to date with GC and explore relations between potential prognostic factors, treatment, and survival.METHODS.Imaging, pathologic, and outcome data were reviewed from 13 patients who were diagnosed with GC and were treated at the Children's Hospital of Philadelphia (CHOP) between 1982 and 2005. All patients had GC confirmed by biopsy. Twelve patients received cranial irradiation, and 8 of those patients received adjuvant chemotherapy. A single patient age 1 year received chemotherapy alone. A review of the literature identified 51 pediatric patients with GC.RESULTS.The progression‐free survival rate in this study was 13% (range, 1.5–43 months), and the overall survival (OS) rate was 64% (range, 6.5–67 months) at 2 years. OS was significantly shorter for patients who presented in the first decade of life (P = .04). The time to progression was prolonged significantly for patients who had no evidence of tumor enhancement on imaging studies (P = .03). When survival data from patients reported in the literature were combined with the CHOP cohort, treatment prolonged OS significantly (P = .003).CONCLUSIONS.The outcome of pediatric patients with GC was extremely poor; however, the current results indicated that treatment may prolong OS. Age < 10 years and contrast enhancement on magnetic resonance imaging studies at diagnosis may be risk factors for shorter survival in pediatric patients with GC. Cancer 2006. © 2006 American Cancer Society.

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Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods

Cited by 270 publications

References 58 publications

Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms

Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms

The “New Math” of Neuroscience: Genetic Tools for Accessing and Electively Manipulating Neurons

Gliomatosis cerebri: 20 Years of experience at the Children's Hospital of Philadelphia

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