Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where E. Todd Weber is active.

Publication


Featured researches published by E. Todd Weber.


Nature | 2012

Aberrant light directly impairs mood and learning through melanopsin-expressing neurons

Tara A. LeGates; Cara M. Altimus; Hui Wang; Hey Kyoung Lee; Sunggu Yang; Haiqing Zhao; Alfredo Kirkwood; E. Todd Weber; Samer Hattar

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep–wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.


Neuroscience Letters | 1997

Neuropeptide Y blocks light-induced phase advances but not delays of the circadian activity rhythm in hamsters

E. Todd Weber; Michael A. Rea

In mammals, the suprachiasmatic nuclei (SCN) are the anatomical site of localization of the light-entrainable circadian clock responsible for the generation of daily rhythms in physiology and behavior. In addition to direct retinohypothalamic innervation, the SCN receive a prominent projection of fibers from the intergeniculate leaflet (IGL) of the thalamus, the geniculohypothalamic tract (GHT), some of which contain the neurotransmitter, neuropeptide Y (NPY). Since the GHT has been suggested to play a role in the modulation of photic entrainment of the SCN circadian clock in rodents, we investigated the effects of local administration of NPY into the region of the SCN on light-induced phase shifts of the free-running activity rhythm in hamsters. Injection of 60 nmol of NPY into the SCN region 10 min prior to light exposure at circadian time 19 completely blocked light-induced phase advances. Similar treatment at circadian time 14 had no significant effect on the magnitude of light-induced phase delays. Injection of NPY at either time point without light exposure did not alter circadian phase. The findings support a modulatory role for NPY in the photic entrainment of the SCN circadian clock.


Neuroscience Letters | 1995

cGMP-dependent protein kinase inhibitor blocks light-induced phase advances of circadian rhythms in vivo

E. Todd Weber; Robert L. Gannon; Michael A. Rea

The suprachiasmatic nucleus (SCN) contains the primary mammalian circadian clock. Light synchronizes these circadian rhythms through a mechanism involving the release of excitatory amino acids (EAA) and synthesis of nitric oxide (NO) in the SCN. In the current study, we investigated whether cGMP-mediated activation of cGMP-dependent protein kinase (PKG) is associated with light-induced phase shifts of the circadian oscillator. Local administration of the specific PKG inhibitor, KT-5823, significantly attenuated light-induced advances in the phase of activity rhythms when administered during late subjective night (CT 19). Similar treatment at CT 14 had no significant effect on light-induced phase delays. These results are the first to implicate PKG in the biochemical pathway(s) responsible for photic phase advances, and suggest a divergence in biochemical pathways involved in photic phase shifts.


Brain Research | 1995

Nitric oxide synthase inhibitor blocks light-induced phase shifts of the circadian activity rhythm, but not c-fos expression in the suprachiasmatic nucleus of the Syrian hamster

E. Todd Weber; Robert L. Gannon; Anna Marie Michel; Martha U. Gillette; Michael A. Rea

Circadian rhythms in mammals are entrained to the environmental light cycle by daily adjustments in the phase of the circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Brief exposure of hamsters maintained under constant darkness to ambient light during subjective nighttime produces both phase shifts of the circadian activity rhythm and characteristic patterns of c-fos protein (Fos) immunoreactivity in the SCN. In this study, we demonstrate that light-induced phase shifts of the circadian activity rhythm are blocked by intracerebroventricular (i.c.v.) injection of the competitive nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not by the inactive isomer, D-NAME. The effects of L-NAME are reversible and dose-related, and are countered by co-injection of arginine, the natural substrate for NOS. While effects on behavioral rhythms are pronounced, similar treatment does not alter the pattern of light-induced Fos immunoreactivity in the SCN. These results suggest that nitric oxide is a component of the signal transduction pathway that communicates photic information to the SCN circadian pacemaker, and that nitric oxide production is either independent of, or downstream from, pathways involved in induction of c-fos expression.


Brain Research | 2006

Potent inhibition of cell proliferation in the hippocampal dentate gyrus of mice by the chemotherapeutic drug thioTEPA.

Robert G. Mignone; E. Todd Weber

Antimitotic drugs used in the chemotherapeutic treatment of cancers induce undesirable but unavoidable side-effects from interruption of normal mitotic processes throughout the body. We have examined whether several such drugs capable of penetrating the blood-brain barrier - thioTEPA and 5-fluorouracil - influence the normal process of cell proliferation underlying neurogenesis in the dentate gyrus of the hippocampus of mice. thioTEPA was found to yield a pronounced dose-related inhibition in cell proliferation, while 5-fluorouracil did not. The magnitude of the inhibition paired with a lack of observable impairment of health in mice indicates a suitable experimental model for elucidating the contributions of hippocampal cell proliferation to cognition and behavior.


European Journal of Pharmacology | 2001

Adenosine A1 receptors regulate the response of the hamster circadian clock to light.

Kurt J Elliott; E. Todd Weber; Michael A. Rea

Circadian rhythms are synchronized to the environmental light-dark cycle by daily, light-induced adjustments in the phase of a biological clock located in the suprachiasmatic nucleus. Ambient light alters the phase of the clock via a direct, glutamatergic projection from retinal ganglion cells. We investigated the hypothesis that adenosine A1 receptors modulate the phase adjusting effect of light on the circadian clock. Systemic administration of the selective adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA), significantly (p<0.05) attenuated light-induced phase delays and advances of the circadian activity rhythm. Selective agonists for the adenosine A2A and adenosine A3 receptors were without effect. The inhibitory effect of CHA on light-induced phase advances was dose-dependent (0.025-1.0 mg/kg, ED(50)=0.3 mg/kg), and this effect was blocked in a dose-dependent (0.005-1.0 mg/kg) manner by the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10 microM) into the region of the suprachiasmatic nucleus significantly attenuated light-induced phase advances, and this effect was also blocked by DPCPX (100 microM). The results suggest that adenosine A1 receptors located in the region of the suprachiasmatic nucleus regulate the response of the circadian clock to the phase-adjusting effects of light.


Behavioural Brain Research | 2010

The chemotherapy agent, thioTEPA, yields long-term impairment of hippocampal cell proliferation and memory deficits but not depression-related behaviors in mice

Christopher M. Mondie; Kelley A. Vandergrift; Courtney L. Wilson; Maria Gulinello; E. Todd Weber

ThioTEPA is a chemotherapeutic agent used in the treatment of cancers, and more recently has been proposed as a component of high-dose therapy for young patients with recurrent malignant brain tumors. We previously demonstrated a significant dose-dependent reduction of cell proliferation in the dentate gyrus of the hippocampus in mice immediately following a 3-day regiment of thioTEPA. The aim of this study was to evaluate the long-term effects of thioTEPA treatment on hippocampal cell proliferation and potential effects on memory deficit or depression-related behavior in C57BL/6J mice. A 3-day regimen of thioTEPA (10mg/kg/d, i.p.) yielded a significant reduction in cell proliferation immediately after treatment as assessed by BrdU incorporation, and none of the labeled progeny that initially survived the treatment were detectable one week later. Following a 3-week rebound in proliferation following treatment, a significant deficit in proliferation reappeared and persisted for at least 21 weeks following treatment. ThioTEPA-treated mice subjected to an object recognition test 1, 2, 3, 4, 8, 12, 20 or 30 weeks following treatment demonstrated significant memory deficits at 12 and 20 weeks. Mice demonstrated a similar deficit in an object placement test when tested 20 weeks following thioTEPA treatment. However, no observable effects on performance in the Porsolt forced swim test or the tail suspension test were observed in thioTEPA-treated mice. Together, these studies suggest that cumulative long-term negative effects of thioTEPA treatment on proliferation of new cells in the dentate gyrus may contribute to cognitive impairments associated with its use in the treatment of cancer.


Behavioural Brain Research | 2013

Chemotherapy drug thioTEPA exacerbates stress-induced anhedonia and corticosteroid responses but not impairment of hippocampal cell proliferation in adult mice.

Courtney L. Wilson; E. Todd Weber

Cancer patients often suffer long-lasting affective and cognitive impairments as a result of chemotherapy treatment. Previous work in our lab has shown deficits in learning and memory and hippocampal cell proliferation in mice lasting up to 20 weeks following acute administration of thioTEPA. In this study, the effects of thioTEPA in conjunction with effects of chronic stress on depression-related behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA administration. Chemotherapy-treated mice showed a diminished sucralose preference compared to controls that was further exacerbated after 2 weeks of daily restraint stress. This intensifying effect was not observed in the Porsolt forced swim test. Moreover, stress-induced corticosteroid responses were exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of the hippocampus was also impaired similarly by prior thioTEPA treatment and by daily restraint stress, with no additive effect. Results suggest that some depression-related impairments may be exacerbated by chemotherapy treatment through altered corticosteroid regulation.


Physiology & Behavior | 2009

Accelerated re-entrainment to advanced light cycles in BALB/cJ mice

Tara A. LeGates; Danielle Dunn; E. Todd Weber

Circadian rhythms in mammals are coordinated by the suprachiasmatic nuclei (SCN) of the hypothalamus, which are most potently synchronized to environmental light-dark cycles. Large advances in the light-dark cycle typically yield gradual advances in activity rhythms on the order of 1-2h per day until re-entrainment is complete due to limitations on the circadian system which are not yet understood. In humans, this delay until re-entrainment is accomplished is experienced as jetlag, with accompanying symptoms of malaise, decreased cognitive performance, sleep problems and gastrointestinal distress. In these experiments, locomotor rhythms of BALB/cJ mice monitored by running wheels were shown to re-entrain to large 6- or 8-hour shifts of the light-dark cycle within 1-2 days, as opposed to the 5-7 days required for C57BL/6J mice. A single-day 6-hour advance of the LD cycle followed by release to constant darkness yielded similar phase shifts, demonstrating that exaggerated re-entrainment is not explained by masking of activity by the light-dark cycle. Responses in BALB/cJ mice were similar when monitored instead by motion detectors, indicating that wheel-running exercise does not influence the magnitude of responses. Neither brief (15 min) light exposure late during subjective nighttime nor 6-hour delays of the light-dark cycle produced exaggerated locomotor phase shifts, indicating that BALB/cJ mice do not merely experience enhanced sensitivity to light. Fos protein was expressed in cells of the SCN following acute light exposure at ZT10 of their previous light-dark cycle, a normally non-responsive time in the circadian cycle, but only in BALB/cJ (and not C57BL/6J) mice that had been subjected two days earlier to a single-day 6-hour advance of the light-dark cycle, indicating that their SCN had been advanced by that treatment. BALB/cJ mice may thus serve as a useful comparative model for studying molecular and physiological processes that limit responsiveness of circadian clocks to photic input.


Physiology & Behavior | 2017

Duration and timing of daily light exposure influence the rapid shifting of BALB/cJ mouse circadian locomotor rhythms

Thomas J. Vajtay; Jeremy J. St. Thomas; Tyrus E. Takacs; Eric G. McGann; E. Todd Weber

Photic entrainment of the murine circadian system can typically be explained with a discrete model in which light exposures near dusk and dawn can either advance or delay free-running rhythms to match the external light cycle period. In most mouse strains, the magnitude of those phase shifts is limited to several hours per day; however, the BALB/cJ mouse can re-entrain to large (6-8hour) phase advances of the light/dark cycle. In this study, we demonstrate that the circadian responses of BALB/cJ mice are dependent on duration as well as timing of light exposure, with significantly larger phase shifts resulting from >6-hour light exposures, yet loss of entrainment to photoperiods of <2-3hours per day or to skeleton photoperiods. Intermittent light exposures of the same total duration but distributed differentially over the same period of time as that of a 6-hour phase advance of the light cycle yielded phase shifts of different magnitudes depending on the pattern of exposure. Both negative and positive masking responses to light and darkness, respectively, were exaggerated in BALB/cJ mice under a T7 light cycle, but were not responsible for their rapid re-entrainment to chronic phase shifting of the light dark cycle. These results collectively suggest that the innately jetlag-resistant BALB/cJ mouse circadian system provides an alternative murine model in which to elucidate the limitations of photic entrainment observed in other commonly used strains of mice.

Collaboration


Dive into the E. Todd Weber's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Gary E. Pickard

University of Nebraska–Lincoln

View shared research outputs
Researchain Logo
Decentralizing Knowledge