Publications by authors named "Andrea Simmons"

43 Publications

Clinical features, neurologic recovery, and risk factors of post-operative posterior fossa syndrome and delayed recovery: A prospective study.

Neuro Oncol 2021 Apr 5. Epub 2021 Apr 5.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.

Methods: Children with medulloblastoma treated at St Jude Children's Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT01878617).

Results: Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12-months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p< 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p< 0.0001) were associated with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23-months after surgery.

Conclusions: Categorizing PFS into types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 with 12-month follow-up were non-ambulatory. Surgical experience was a major modifiable contributor to the development of PFS.
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http://dx.doi.org/10.1093/neuonc/noab030DOI Listing
April 2021

A comprehensive computational model of animal biosonar signal processing.

PLoS Comput Biol 2021 Feb 17;17(2):e1008677. Epub 2021 Feb 17.

Department of Neuroscience and Carney Institute for Brain Science, Brown University Providence, United States of America.

Computational models of animal biosonar seek to identify critical aspects of echo processing responsible for the superior, real-time performance of echolocating bats and dolphins in target tracking and clutter rejection. The Spectrogram Correlation and Transformation (SCAT) model replicates aspects of biosonar imaging in both species by processing wideband biosonar sounds and echoes with auditory mechanisms identified from experiments with bats. The model acquires broadband biosonar broadcasts and echoes, represents them as time-frequency spectrograms using parallel bandpass filters, translates the filtered signals into ten parallel amplitude threshold levels, and then operates on the resulting time-of-occurrence values at each frequency to estimate overall echo range delay. It uses the structure of the echo spectrum by depicting it as a series of local frequency nulls arranged regularly along the frequency axis of the spectrograms after dechirping them relative to the broadcast. Computations take place entirely on the timing of threshold-crossing events for each echo relative to threshold-events for the broadcast. Threshold-crossing times take into account amplitude-latency trading, a physiological feature absent from conventional digital signal processing. Amplitude-latency trading transposes the profile of amplitudes across frequencies into a profile of time-registrations across frequencies. Target shape is extracted from the spacing of the object's individual acoustic reflecting points, or glints, using the mutual interference pattern of peaks and nulls in the echo spectrum. These are merged with the overall range-delay estimate to produce a delay-based reconstruction of the object's distance as well as its glints. Clutter echoes indiscriminately activate multiple parts in the null-detecting system, which then produces the equivalent glint-delay spacings in images, thus blurring the overall echo-delay estimates by adding spurious glint delays to the image. Blurring acts as an anticorrelation process that rejects clutter intrusion into perceptions.
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http://dx.doi.org/10.1371/journal.pcbi.1008677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888678PMC
February 2021

Height, weight, and cardiovascular effects of stimulants on children with brain tumors.

Pediatr Blood Cancer 2021 Jan 13;68(1):e28740. Epub 2020 Oct 13.

Department of Neuro-Oncology, MD Anderson Cancer Center, Houston, Texas.

Introduction: Children with brain tumors may develop inattention, slow processing, and hypersomnia. Stimulant medications improve these problems, but their effect on growth, heart rate, and blood pressure (BP) are inadequately explored.

Procedure: We retrospectively studied children with brain tumors treated at our institution that had data available for 1 year pre and 2 years on stimulant treatment. Tumor location, gender, radiation treatment (RT), age at RT, drug type, and hormone therapy were variables of interest.

Results: We identified 65 children (35 males) that fulfilled eligibility criteria. Focal RT was utilized in 58; 11 additionally had whole brain RT; and seven received no RT. Thirty were treated for hypersomnia and inattention, eight for hypersomnia alone, and rest for inattention. Modafinil was the first drug in 18 (27.7%), and methylphenidate in the others. Forty-seven (72.3%), 45 (69.2%), and 49 (75.4%) were on thyroxine, cortisone, and growth hormones, respectively. There was no difference in pre- and post-stimulant body mass index (BMI), heart rate, and BP. There was also no difference between modafinil and methylphenidate groups. Rate of height acquisition slowed on stimulants (P = .0096). Thyroxine treatment correlated with increase in BMI after stimulants (P = .04). Younger age (P = .0003) and higher prestimulant BMI (P = .0063) correlated with increased heart rate on stimulants, while higher age at RT (P =.016) correlated with elevated systolic BP on stimulants. No associations were found with height acquisition and diastolic BP.

Conclusion: Stimulants are well tolerated by children with brain tumors that are appropriately managed for endocrine deficiencies, but may reduce the trajectory of height attainment.
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http://dx.doi.org/10.1002/pbc.28740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872133PMC
January 2021

Long-latency optical responses from the dorsal inferior colliculus of Seba's fruit bat.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2020 11 10;206(6):831-844. Epub 2020 Aug 10.

Department of Neuroscience, Brown University, 185 Meeting St, Providence, RI, 02912, USA.

We used a novel microendoscope system to record simultaneously optical activity (fluorescence of a calcium indicator dye) and electrical activity (multi-unit activity and local field potentials) from the dorsal inferior colliculus of the echolocating bat, Carollia perspicillata. Optically recorded calcium responses to wide-band noise and to frequency-modulated bursts were recorded at probe depths down to 1300 µm, with the majority of active sites encountered at more shallow depths down to 800 µm. Calcium activity exhibited long latencies, within the time span of 50-100 ms after stimulus onset, significantly longer than onset latencies of either multi-unit activity or local field potentials. Latencies and amplitude/latency trading of these electrical responses were consistent with those seen in standard electrophysiological recordings, confirming that the microendoscope was able to record both neural and optical activity successfully. Optically recorded calcium responses rose and decayed slowly and were correlated in time with long-latency negative deflections in local field potentials. These data suggest that calcium-evoked responses may reflect known, sustained inhibitory interactions in the inferior colliculus.
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http://dx.doi.org/10.1007/s00359-020-01441-7DOI Listing
November 2020

Transition experiences of nurses as students and new graduate nurses in a collaborative nurse residency program.

J Prof Nurs 2020 Jan - Feb;36(1):69-75. Epub 2019 Jun 12.

Clarke University, 1550 Clarke Drive, Dubuque, IA, USA.

Background: A small Midwestern college of nursing and an affiliate hospital partnered to design a nurse residency program where students are extended pre-hire job offers in a practice area of their choice and are then partnered with a preceptor who they will work with in a clinical immersion experience during the last semester of their nursing program and in their orientation period as new nurses.

Purpose: The purpose of this qualitative, phenomenological study was to explore the lived experiences of a cohort of nurses as students and new graduate nurses during transition in this collaborative nurse residency program.

Method: A transcendental phenomenological qualitative approach using Meleis' Transition Experience Theory as a theoretical framework is used for this study.

Results: Themes of feeling overwhelmed, supported, and confident were identified. A finding unique to the literature and this nurse residency program model is a theme of overwhelming support.

Conclusions: This information can be used to improve the nurse residency program and its outcomes and also further the advancement of nursing knowledge of the transition experience of new nurses.
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http://dx.doi.org/10.1016/j.profnurs.2019.06.006DOI Listing
October 2020

Big brown bats are challenged by acoustically-guided flights through a circular tunnel of hoops.

Sci Rep 2020 01 21;10(1):832. Epub 2020 Jan 21.

Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, Rhode Island, 02912-9067, United States.

Mines and caves provide essential roosting places for bats, but often they are obstructed to prevent entry by humans. To allow bats to access their roosts, metal corrugated culvert pipes are sometimes installed. Wildlife surveys indicate, however, that bats may abandon caves having corrugated culvert entrances. Culverts may be confusing to bats due to the complex patterns of echoes returned by the regular, ring-like corrugations. We tested the hypothesis that a circular tunnel composed of successive hoops is difficult for big brown bats (Eptesicus fuscus) to navigate. Experiments challenged bats with flights through a tunnel of round plastic hoops or a corridor flanked left and right by rows of plastic hanging chains. The bats swerved sideways and left the pathway on more flights in the hoop tunnel compared to only rarely in the chain corridor. Even during successful flights through the hoops, bats changed the temporal patterning of their echolocation pulses to compress them into more sonar sound groups. From prior research, this active reaction is an indicator of a perceptually more difficult task. To allow bats access to mines through culverts without affecting their echolocation behavior, smoothing or masking the regular corrugations inside with concrete may be effective.
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http://dx.doi.org/10.1038/s41598-020-57632-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972939PMC
January 2020

Echolocation while drinking: Pulse-timing strategies by high- and low-frequency FM bats.

PLoS One 2019 23;14(12):e0226114. Epub 2019 Dec 23.

Department of Neuroscience, Brown University, Providence, RI, United States of America.

During nightly foraging activity, echolocating bats drink by flying low over the water surface and dipping the lower jaw while avoiding further bodily contact with the water. This task poses different sensorimotor challenges than flying in the open to forage for insects. Of interest is how bats adjust the timing of their echolocation pulses to accommodate the surrounding scene, from the progressively nearer water surface itself to objects at longer distances. Drinking behavior has been described in only a few of the roughly 1,000 echolocating bat species, and in none of the 110 species in the Indian subcontinent. Here, we describe how bats emitting frequency-modulated (FM) echolocation pulses behaved while drinking from a swimming pool in urban northeast India. At least two different bat species were present, using 1st-harmonic frequencies sweeping down to about 35 Hz ("low frequency") and down to about 50 kHz ("high frequency"), separable at a 40 kHz boundary. Over entire drinking maneuvers, intervals between broadcast pulses accommodate both the proximate task of registering the water surface while drinking and registering echoes from the farther reaches of the scene. During approach to the water, both low and high frequency bats emit longer, more stable interpulse intervals that matched the time interval covering echo arrival-times out to the frequency-dependent maximum operating range. High frequency bats use shorter interpulse intervals than low frequency bats, consistent with the shorter operating range at higher frequencies. Bats then accelerate their pulse rate to guide the dive down to drinking, with low frequency bats continuing to decrease pulse intervals and high frequency bats maintaining a more steady interval during the drinking buzz. The circumstance that both groups were engaged in the same task made this a natural experiment on the behavior during approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226114PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927664PMC
March 2020

Frequency-modulated up-chirps produce larger evoked responses than down-chirps in the big brown bat auditory brainstem.

J Acoust Soc Am 2019 09;146(3):1671

Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.

In many mammals, upward-sweeping frequency-modulated (FM) sounds (up-chirps) evoke larger auditory brainstem responses than downward-sweeping sounds (down-chirps). To determine if similar effects occur in FM echolocating bats, auditory evoked responses (AERs) in big brown bats in response to up-chirps and down-chirps at different chirp durations and levels were recorded. Even though down-chirps are the biologically relevant stimulus for big brown bats, up-chirps typically evoked larger peaks in the AER, but with some exceptions at the shortest chirp durations. The up-chirp duration that produced the largest AERs and the greatest differences between up-chirps and down-chirps varied between individual bats and stimulus levels. Cross-covariance analyses using the entire AER waveform confirmed that amplitudes were typically larger to up-chirps than down-chirps at supra-threshold levels, with optimal durations around 0.5-1 ms. Changes in response latencies with stimulus levels were consistent with previous estimates of amplitude-latency trading. Latencies tended to decrease with increasing up-chirp duration and increase with increasing down-chirp duration. The effects of chirp direction on AER waveforms are generally consistent with those seen in other mammals but with small differences in response patterns that may reflect specializations for FM echolocation.
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http://dx.doi.org/10.1121/1.5126022DOI Listing
September 2019

Tadpole bioacoustics: Sound processing across metamorphosis.

Behav Neurosci 2019 Dec 26;133(6):586-601. Epub 2019 Aug 26.

Brown University.

Many species of anuran amphibians (frogs and toads) undergo metamorphosis, a developmental process during which external and internal body morphologies transform dramatically as the animal transitions to a new ecosystem (from aquatic to terrestrial) and develops new behavior patterns (from filter-feeding to active pursuit of moving prey; from mostly mute to highly vocal). All sensory systems transform to some extent during metamorphosis, even in those "primitive" anuran species that remain fully aquatic in adult life. In this article, I review what is known about the development of the auditory system in anuran tadpoles. I identify crucial developmental windows for major maturational events in the ear and brainstem that showcase the structural and physiological reorganization of the substrates for hearing airborne sounds as the animal navigates the metamorphic transition. I argue that auditory development is dynamic and nonlinear, and I point out areas for future investigation. Understanding metamorphosis can shed light on how organisms adapt to major environmental challenges. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/bne0000340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856408PMC
December 2019

Introduction to the special issue on neuroethology.

Behav Neurosci 2019 Jun;133(3):265-266

Johns Hopkins University.

This special issue highlights some recent advances in neuroethology based on research presented at the 13th International Congress of Neuroethology and associated satellite symposia in Brisbane, Australia, on July 15-20, 2018. The discipline of neuroethology combines methods and concepts from ethology with those from neurobiology to develop a comparative analysis of the mechanisms of behavior that takes into account a species' ecology and evolutionary history. In his 1951 book , Nobel Prize winner Niko Tinbergen called on ethologists and neurophysiologists to join forces to search for mechanisms of motivated behaviors. He used the term "ethophysiology" to describe this integrative research approach, which he felt was crucial for developing a full understanding of behavior in all its complexities. At that time, "the ethologists were as naive about the neurophysiological significance of their findings as the neurophysiologists were about the behavioral implications of theirs" (Hoyle, 1984, p. 371). To rectify these limitations and to move forward, some of the earliest neuroethological research focused on understanding cellular mechanisms underlying the ethological concepts of releasers (sign stimuli) and fixed action patterns in species such as locusts and toads (Ewert, 1980; Hoyle, 1984). The breadth of neuroethological research soon expanded to include many other species, particularly those with distinct sensory or motor specializations (echolocating bats, electric fish, barn owls; Ewert, Capranica, & Ingle, 1983), as well as to understand neural mechanisms of more "general" behaviors, such as learning, memory, navigation, and communication. Molecular genetic, anatomical, and computational approaches are also part of the neuroethologist's toolbox. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/bne0000327DOI Listing
June 2019

Big brown bats (Eptesicus fuscus) successfully navigate through clutter after exposure to intense band-limited sound.

Sci Rep 2018 09 10;8(1):13555. Epub 2018 Sep 10.

Department of Neuroscience, Brown University, Providence, RI, 02912, USA.

Echolocating big brown bats fly, orient, forage, and roost in cluttered acoustic environments in which aggregate sound pressure levels can be as intense as 100 to 140 dB SPL, levels that would impair auditory perception in other terrestrial mammals. We showed previously that bats exposed to intense wide-band sound (116 dB SPL) can navigate successfully through dense acoustic clutter. Here, we extend these results by quantifying performance of bats navigating through a cluttered scene after exposure to intense band-limited sounds (bandwidths 5-25 kHz, 123 dB SPL). Behavioral performance was not significantly affected by prior sound exposure, with the exception of one bat after exposure to one sound. Even in this outlying case, performance recovered rapidly, by 10 min post-exposure. Temporal patterning of biosonar emissions during successful flights showed that bats maintained their individual strategies for navigating through the cluttered scene before and after exposures. In unsuccessful flights, interpulse intervals were skewed towards shorter values, suggesting a shift in strategy for solving the task rather than a hearing impairment. Results confirm previous findings that big brown bats are not as susceptible to noise-induced perceptual impairments as are other terrestrial mammals exposed to sounds of similar intensity and bandwidth.
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http://dx.doi.org/10.1038/s41598-018-31872-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131230PMC
September 2018

TLR agonist combinations that stimulate Th type I polarizing responses from human neonates.

Innate Immun 2018 05 19;24(4):240-251. Epub 2018 Apr 19.

Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, NY, USA.

Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants. APC-specific surface expression levels of costimulatory markers CD40, CD83 and PD-L1 were assessed by flow cytometry. Whole blood assays were included to account for the effect of plasma inhibitory factors and APC intracellular TNF-α and IL-12p40 secretions were measured. We found robust Th1 polarizing IL-12p70, IFN-γ and IFN-α responses when cord blood APCs were stimulated with TLR agonist combinations that contained Poly I:C, Monophosphoryl Lipid A (MPLA) or R848. Addition of class A CpG oligonucleotide (ODN) to Th1 polarizing TLR agonist combinations significantly reduced cord blood IL-12p70 and IFN-γ levels and addition of a TLR2 agonist induced significantly high Th2 polarizing IL-13. Multi-TLR agonist combinations that included R848 induced lower inhibitory PD-L1 expression on cord blood classical dendritic cells than CpG ODN-containing combinations. Incorporation of combination adjuvants containing TLR3, TLR4 and TLR7/8 agonists to neonatal vaccines may be an effective strategy to overcome neonatal Th2 bias.
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http://dx.doi.org/10.1177/1753425918771178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830928PMC
May 2018

Prevalence, risk factors, and response to treatment for hypersomnia of central origin in survivors of childhood brain tumors.

J Neurooncol 2018 Jan 8;136(2):379-384. Epub 2017 Nov 8.

Division of Nursing Research, Department of Pediatrics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.

Daytime sleepiness is recognized in childhood brain tumor survivors. Our objective was to determine prevalence, risk factors for PSG/MLST proven hypersomnia/narcolepsy, and response to stimulants in childhood brain tumor survivors. Standard PSG/MSLT criteria were used to diagnose hypersomnia/narcolepsy. Medical records of brain tumor survivors having undergone a PSG/MSLT were reviewed for the diagnostic code of hypersomnia/narcolepsy. Survivors with hypersomnia/narcolepsy were matched with 2-3 survivors without reported hypersomnia/narcolepsy by age at tumor diagnosis, gender, and time from tumor diagnosis. Between January 2000 to April 2015, 39 of the 2336 brain tumor patients treated at our institution were diagnosed with hypersomnia/narcolepsy for a prevalence rate of 1670/100,000. Hypersomnia/narcolepsy was diagnosed at a median of 6.1 years (range 0.4-13.2) from tumor diagnosis and 4.7 years (range - 1.5 to 10.4) from cranial radiation. Midline tumor location (OR 4.6, CI 1.7-12.2, p = 0.002) and anti-epilepsy drug (AED) use (OR 11, CI 2.4-54) correlated with hypersomnia/narcolepsy while radiation dose > 30 Gray trended towards significance (OR 1.8, CI 0.9-3.6); posterior fossa tumor location reduced the risk (OR 0.1, CI 0.04-0.5, p = 0.002). AED use also correlated with midline tumor location. Thirty-seven survivors were treated with stimulants and reported improved wakefulness and school performance [response rate CI 0.97 (0.86-0.99) and 0.83 (0.65-0.94)]. Prevalence of hypersomnia/narcolepsy among childhood brain tumor survivors was higher than the general population. Tumor location and radiation dose were possible risk factors, and stimulants were reported to be beneficial.
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http://dx.doi.org/10.1007/s11060-017-2662-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814140PMC
January 2018

Big brown bats (Eptesicus fuscus) maintain hearing sensitivity after exposure to intense band-limited noise.

J Acoust Soc Am 2017 03;141(3):1481

Department of Neuroscience, Brown University, 185 Meeting Street, Providence, Rhode Island 02912, USA.

Thresholds to short-duration narrowband frequency-modulated (FM) sweeps were measured in six big brown bats (Eptesicus fuscus) in a two-alternative forced choice passive listening task before and after exposure to band-limited noise (lower and upper frequencies between 10 and 50 kHz, 1 h, 116-119 dB sound pressure level root mean square; sound exposure level 152 dB). At recovery time points of 2 and 5 min post-exposure, thresholds varied from -4 to +4 dB from pre-exposure threshold estimates. Thresholds after sham (control) exposures varied from -6 to +2 dB from pre-exposure estimates. The small differences in thresholds after noise and sham exposures support the hypothesis that big brown bats do not experience significant temporary threshold shifts under these experimental conditions. These results confirm earlier findings showing stability of thresholds to broadband FM sweeps at longer recovery times after exposure to broadband noise. Big brown bats may have evolved a lessened susceptibility to noise-induced hearing losses, related to the special demands of echolocation.
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http://dx.doi.org/10.1121/1.4976820DOI Listing
March 2017

Variability of Rheotaxis Behaviors in Larval Bullfrogs Highlights Species Diversity in Lateral Line Function.

PLoS One 2016 21;11(11):e0166989. Epub 2016 Nov 21.

Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, Rhode Island, 02912, United States of America.

The morphology and distribution of lateral line neuromasts vary between ecomorphological types of anuran tadpoles, but little is known about how this structural variability contributes to differences in lateral-line mediated behaviors. Previous research identified distinct differences in one such behavior, positive rheotaxis towards the source of a flow, in two tadpole species, the African clawed frog (Xenopus laevis; type 1) and the American bullfrog (Rana catesbeiana; type 4). Because these two species had been tested under different flow conditions, we re-evaluated these findings by quantifying flow-sensing behaviors of bullfrog tadpoles in the same flow field in which X. laevis tadpoles had been tested previously. Early larval bullfrog tadpoles were exposed to flow in the dark, in the presence of a discrete light cue, and after treatment with the ototoxin gentamicin. In response to flow, tadpoles moved downstream, closer to a side wall, and higher in the water column, but they did not station-hold. Tadpoles exhibited positive rheotaxis, but with long latencies, low to moderate accuracy, and considerable individual variability. This is in contrast to the robust, stereotyped station-holding and accurate rheotaxis of X. laevis tadpoles. The presence of a discrete visual cue and gentamicin treatment altered spatial positioning and disrupted rheotaxis in both tadpole species. Species differences in lateral-line mediated behaviors may reflect differences in neuromast number and distribution, life history, or perceptual salience of other environmental cues.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166989PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117756PMC
June 2017

Echolocation behavior in big brown bats is not impaired after intense broadband noise exposures.

J Exp Biol 2016 10 10;219(Pt 20):3253-3260. Epub 2016 Aug 10.

Department of Neuroscience, Brown University, Providence, RI 02912, USA

Echolocating bats emit trains of intense ultrasonic biosonar pulses and listen to weaker echoes returning from objects in their environment. Identification and categorization of echoes are crucial for orientation and prey capture. Bats are social animals and often fly in groups in which they are exposed to their own emissions and to those from other bats, as well as to echoes from multiple surrounding objects. Sound pressure levels in these noisy conditions can exceed 110 dB, with no obvious deleterious effects on echolocation performance. Psychophysical experiments show that big brown bats (Eptesicus fuscus) do not experience temporary threshold shifts after exposure to intense broadband ultrasonic noise, but it is not known if they make fine-scale adjustments in their pulse emissions to compensate for any effects of the noise. We investigated whether big brown bats adapt the number, temporal patterning or relative amplitude of their emitted pulses while flying through an acoustically cluttered corridor after exposure to intense broadband noise (frequency range 10-100 kHz; sound exposure level 152 dB). Under these conditions, four bats made no significant changes in navigation errors or in pulse number, timing and amplitude 20 min, 24 h or 48 h after noise exposure. These data suggest that big brown bats remain able to perform difficult echolocation tasks after exposure to ecologically realistic levels of broadband noise.
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http://dx.doi.org/10.1242/jeb.143578DOI Listing
October 2016

Transcranial Doppler Screening in a Regional Care Network for Sickle Cell Disease in the United Kingdom.

J Pediatr Hematol Oncol 2016 10;38(7):517-24

*Center for Genomics and Child Health, Barts and The London School of Medicine, London †Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool Departments of ‡Pediatrics §Neuroradiology, Royal London Hospital, Barts Health NHS Trust, London ∥Department of Pediatrics, Newham University Hospital, Barts Health NHS Trust, London ¶Newham Sickle Cell and Thalassemia Community Centre, London #Department of Pediatrics, Whipps Cross University Hospital, Barts Health NHS Trust, London **Department of Pediatrics, Basildon University Hospital NHS Trust, Basildon, Essex ††Department of Hematology, Queens Hospital, Romford NHS Trust, Romford, Essex, UK.

The risk of stroke in children screened with transcranial Doppler ultrasound in the United Kingdom is not known. We evaluated a clinician-led program using a risk assessment modified from the STOP protocol. High-risk classification included abnormal velocities in the anterior cerebral artery, and single abnormal scan if initial velocity >220 cm/s (high abnormal) or if preceded by at least 2 conditional scans. In total, 1653 scans were performed in 542 children, followed for 2235 patient-years. Fifty-eight (10.7%) high-risk subjects were identified, including 18 (31%) with high abnormal, and 15 (26%) with previous conditional scans. In 2 (3%), abnormal velocity was restricted to the anterior cerebral artery. The estimated proportion of children at high risk, scanned before 6 years of age was >20%. There were 4 cases of acute ischemic stroke (AIS) and 2 of acute hemorrhagic stroke. The incidence of all stroke, AIS, and acute hemorrhagic stroke were 0.27, 0.18, and 0.09 per 100 patient-years, respectively. The proportion of children at high risk is higher than most previous estimates, partly as a result of our modified risk assessment. About 2 children per 1000 screened with transcranial Doppler ultrasound progress to AIS.
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http://dx.doi.org/10.1097/MPH.0000000000000633DOI Listing
October 2016

Broadband noise exposure does not affect hearing sensitivity in big brown bats (Eptesicus fuscus).

J Exp Biol 2016 Apr;219(Pt 7):1031-40

Department of Neuroscience, Brown University, Providence, RI 02912, USA.

In many vertebrates, exposure to intense sounds under certain stimulus conditions can induce temporary threshold shifts that reduce hearing sensitivity. Susceptibility to these hearing losses may reflect the relatively quiet environments in which most of these species have evolved. Echolocating big brown bats (Eptesicus fuscus) live in extremely intense acoustic environments in which they navigate and forage successfully, both alone and in company with other bats. We hypothesized that bats may have evolved a mechanism to minimize noise-induced hearing losses that otherwise could impair natural echolocation behaviors. The hearing sensitivity of seven big brown bats was measured in active echolocation and passive hearing tasks, before and after exposure to broadband noise spanning their audiometric range (10-100 kHz, 116 dB SPL re. 20 µPa rms, 1 h duration; sound exposure level 152 dB). Detection thresholds measured 20 min, 2 h or 24 h after exposure did not vary significantly from pre-exposure thresholds or from thresholds in control (sham exposure) conditions. These results suggest that big brown bats may be less susceptible to temporary threshold shifts than are other terrestrial mammals after exposure to similarly intense broadband sounds. These experiments provide fertile ground for future research on possible mechanisms employed by echolocating bats to minimize hearing losses while orienting effectively in noisy biological soundscapes.
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http://dx.doi.org/10.1242/jeb.135319DOI Listing
April 2016

Auditory brainstem responses of Japanese house bats (Pipistrellus abramus) after exposure to broadband ultrasonic noise.

J Acoust Soc Am 2015 Oct;138(4):2430-7

Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.

Echolocating bats forage and navigate within an intense soundscape containing their own sonar sounds as well as sounds from other bats. To determine how the bat's auditory system copes with these high noise levels, auditory brainstem responses (ABR) were measured in the Japanese house bat, Pipistrellus abramus, before and after exposure to ultrasonic noise (30 min duration). Noise spectral content (10-80 kHz) and level (90 dB sound pressure level) are within the ranges these bats experience in their natural environment. ABR thresholds to test frequencies of 20, 40, and 80 kHz did not vary significantly between pre-exposure and post-exposure times of 0 and 30 min. Amplitudes and latencies of the P3 wave at suprathreshold were not significantly affected by noise exposure. These data show that the bat's hearing is not compromised when exposed to background sounds similar in wideband frequency content and sound level to what the animal encounters naturally. These results provide a baseline for examining how the bat's auditory system deals with other intense sounds, such as those emitted by anthropogenic sources or those producing temporary threshold shifts in other mammals.
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http://dx.doi.org/10.1121/1.4931901DOI Listing
October 2015

Representation of particle motion in the auditory midbrain of a developing anuran.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2015 Jul 17;201(7):681-9. Epub 2015 May 17.

Department of Cognitive, Linguistic and Psychological Sciences and Department of Neuroscience, Brown University, 1821, Providence, RI, 02912, USA,

In bullfrog tadpoles, a "deaf period" of lessened responsiveness to the pressure component of sounds, evident during the end of the late larval period, has been identified in the auditory midbrain. But coding of underwater particle motion in the vestibular medulla remains stable over all of larval development, with no evidence of a "deaf period." Neural coding of particle motion in the auditory midbrain was assessed to determine if a "deaf period" for this mode of stimulation exists in this brain area in spite of its absence from the vestibular medulla. Recording sites throughout the developing laminar and medial principal nuclei show relatively stable thresholds to z-axis particle motion, up until the "deaf period." Thresholds then begin to increase from this point up through the rest of metamorphic climax, and significantly fewer responsive sites can be located. The representation of particle motion in the auditory midbrain is less robust during later compared to earlier larval stages, overlapping with but also extending beyond the restricted "deaf period" for pressure stimulation. The decreased functional representation of particle motion in the auditory midbrain throughout metamorphic climax may reflect ongoing neural reorganization required to mediate the transition from underwater to amphibious life.
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http://dx.doi.org/10.1007/s00359-015-1015-6DOI Listing
July 2015

Auditory brainstem response of the Japanese house bat (Pipistrellus abramus).

J Acoust Soc Am 2015 Mar;137(3):1063-8

Department of Neuroscience, Brown University, Providence, Rhode Island 02912.

Auditory brainstem responses (ABR) to high frequencies encompassing the species' vocal repertoire were recorded from the inferior colliculus of the Japanese house bat, Pipistrellus abramus. Amplitudes of tone pips were systematically decreased to obtain a threshold of response at different tone frequencies. The compiled audiogram has a broad U-shape over the frequency range from 4 to 80 kHz, with low thresholds between 20 and 50 kHz. The most sensitive frequency region of 35-50 kHz occurs at the quasi-constant-frequency terminal portion of the bat's downsweeping frequency-modulated echolocation pulses. Good sensitivity extending down to 20 kHz includes the frequency range of the first harmonic of communication sounds. The ABR audiogram does not show distinct, narrow peaks of greater sensitivity at the dominant frequencies in species vocalizations. Latencies of peaks in ABR responses lengthened as stimuli were attenuated. At 40 kHz, response latencies traded with amplitude by -7 to -9 μs/dB, a value smaller than measured in another frequency-modulated bat using lower frequencies for echolocation. These results have implications for understanding the significance of amplitude-latency trading in a comparative context.
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http://dx.doi.org/10.1121/1.4908212DOI Listing
March 2015

Flow sensing in developing Xenopus laevis is disrupted by visual cues and ototoxin exposure.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2015 Feb 8;201(2):215-33. Epub 2014 Nov 8.

Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI, 02912, USA,

We explored how lateral line cues interact with visual cues to mediate flow sensing behaviors in the nocturnal developing frog, Xenopus laevis, by exposing animals to current flows under different lighting conditions and after exposure to the ototoxin gentamicin. Under dark conditions, Xenopus tadpoles move downstream at the onset of current flow, then turn, and orient toward the direction of the flow with high accuracy. Postmetamorphic froglets also exhibit positive rheotaxis but with less accuracy and longer latency. The addition of discrete light cues to an otherwise dark environment disrupts rheotaxis and positioning. Orientation is less accurate, latency to orient is longer, and animals do not move as far downstream in the presence of light. Compared with untreated tadpoles tested in the dark, tadpoles exposed to gentamicin show less accurate rheotaxis with longer latency and do not move as far downstream in response to flow. These effects are compounded by the presence of light cues. The disruptive effects of light on flow sensing in Xenopus emphasize the disturbances to natural behaviors that may be produced by anthropogenic illumination in nocturnal habitats.
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http://dx.doi.org/10.1007/s00359-014-0957-4DOI Listing
February 2015

Deferasirox for iron chelation in multitransfused children with sickle cell disease; long-term experience in the East London clinical haemoglobinopathy network.

Eur J Haematol 2015 Apr 24;94(4):336-42. Epub 2014 Sep 24.

Department of Paediatric Haematology, Royal London Hospital, London, UK.

Deferasirox (DFX) has been licensed for iron chelation in patients with sickle cell disease (SCD), but there is limited data on its long-term efficacy and safety in children. This retrospective study included 62 regularly transfused children managed in the East London and Essex Clinical Haemoglobinopathy Network (mean age 9.2 ± 3.2 yr). Efficacy measurements consisted of monthly serum ferritin (SF) and annual R2 MRI-estimated liver iron concentration (LIC), and safety markers included serum creatinine and alanine aminotransferase (ALT). The mean duration of DFX treatment was 2.5 ± 1.4 yr, and mean dose at 36 months was 25 mg/kg/d. Mean SF at initiation of treatment was 2542 ± 952 ng/mL and increased to 4691 ± 2255 ng/mL at 36 months (P = 0.05). Mean LIC on first scan was 10.3 mg/g dry weight and did not decrease significantly on follow-up scans. There was a significant correlation between relative change in LIC and in SF (R(2) = 0.66, P < 0.001). Reversible transaminitis episodes, probably due to drug-induced hepatitis, were noted in 53% of patients. Responses to an adherence and acceptability questionnaire indicated that more than 50% of children had difficulties in taking DFX, commonly because of unpleasant taste. Our results show that more than 50% of children with SCD have inadequate control of iron overload with DFX. It is not clear whether this is because of frequent dose interruptions, poor tolerability and adherence, or poor efficacy of the drug. We recommend further studies to confirm these findings and to optimise iron chelation in this population.
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http://dx.doi.org/10.1111/ejh.12435DOI Listing
April 2015

Lean methodology improves efficiency in outpatient academic uro-oncology clinics.

Urology 2014 May 25;83(5):992-7. Epub 2014 Mar 25.

Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Objective: To determine if lean methodology, an industrial engineering tool developed to optimize manufacturing efficiency, can successfully be applied to improve efficiencies and quality of care in a hospital-based high-volume uro-oncology clinic.

Methods: Before the lean initiative, baseline data were collected on patient volumes, wait times, cycle times (patient arrival to discharge), nursing assessment time, patient teaching, and physician ergonomics (via spaghetti diagram). Value stream analysis and a rapid improvement event were carried out, and significant changes were made to patient check-in, work areas, and nursing face time. Follow-up data were obtained at 30, 60, and 90 days. The Student t test was used for analysis to compare performance metrics with baseline.

Results: The median cycle time before the lean initiative was 46 minutes. This remained stable at 46 minutes at 30 days but improved to 35 minutes at 60 days and 41 minutes at 90 days. Shorter wait times allowed for increased nursing and physician face time. The average length of the physician assessment increased from 7.5 minutes at baseline to 10.6 minutes at 90 days. The average proportion of value-added time compared with the entire clinic visit increased from 30.6% at baseline to 66.3% at 90 days.

Conclusion: Using lean methodology, we were able to shorten the patient cycle time and the time to initial assessment as well as integrate both an initial registered nurse assessment and registered nurse teaching to each visit. Lean methodology can effectively be applied to improve efficiency and patient care in an academic outpatient uro-oncology clinic setting.
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http://dx.doi.org/10.1016/j.urology.2013.11.048DOI Listing
May 2014

"To ear is human, to frogive is divine": Bob Capranica's legacy to auditory neuroethology.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2013 Mar 14;199(3):169-82. Epub 2012 Dec 14.

Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI, 02912, USA.

Bob Capranica was a towering figure in the field of auditory neuroethology. Among his many contributions are the exploitation of the anuran auditory system as a general vertebrate model for studying communication, the introduction of a signal processing approach for quantifying sender-receiver dynamics, and the concept of the matched filter for efficient neural processing of complex vocal signals. In this paper, meant to honor Bob on his election to Fellow of the International Society for Neuroethology, I provide a description and analysis of some of his most important research, and I highlight how the concepts and data he contributed still inspire neuroethology today.
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http://dx.doi.org/10.1007/s00359-012-0786-2DOI Listing
March 2013

Particle motion is broadly represented in the vestibular medulla of the bullfrog across larval development.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2012 Apr 24;198(4):253-66. Epub 2011 Dec 24.

Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Box 1821, Providence, RI 02912, USA.

In their shallow-water habitats, bullfrog (Rana catesbeiana) tadpoles are exposed to both underwater and airborne sources of acoustic stimulation. We probed the representation of underwater particle motion throughout the tadpole's dorsal medulla to determine its spatial extent over larval life. Using neurobiotin-filled micropipettes, we recorded neural activity to z-axis particle motion (frequencies of 40-200 Hz) in the medial vestibular nucleus, lateral vestibular nucleus, dorsal medullary nucleus (DMN), and along the dorsal arcuate pathway. Sensitivity was comparable in the medial and lateral vestibular nuclei, with estimated thresholds between 0.016 and 12.5 μm displacement. Neither best responding frequency nor estimated threshold varied significantly over larval stage. Transport of neurobiotin from active recording sites was also stable over development. The DMN responded poorly to z-axis particle motion, but did respond to low-frequency pressure stimulation. These data suggest that particle motion is represented widely and stably in the tadpole's vestibular medulla. This is in marked contrast to the representation of pressure stimulation in the auditory midbrain, where a transient "deaf period" of non-responsiveness and decreased connectivity occurs immediately prior to metamorphic climax. We suggest that, in bullfrogs, sensitivity to particle motion and to pressure follows different developmental trajectories.
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http://dx.doi.org/10.1007/s00359-011-0705-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310269PMC
April 2012

Movements of Rana catesbeiana tadpoles in weak current flows resemble a directed random walk.

J Exp Biol 2011 Jul;214(Pt 14):2297-307

Department of Cognitive, Linguistic, Brown University, Providence, RI 02912, USA.

Current flow is an important biological stimulus for larval anuran amphibians, but little is known about how it is perceived. We quantified behavioral responses to controlled water flow in the bullfrog tadpole (Rana catesbeiana) at developmental stages prior to metamorphic climax, and examined the contribution of a functioning lateral line system to these behaviors. Tadpoles at these developmental stages show a significant preference for the sides and bottom of a flow tank. In response to water flow at three different rates, they exhibit a significant, time-dependent tendency to move downstream, away from the source of the flow, and to remain in areas where flow is minimized. The consistency of these behaviors at all tested flow rates suggests that the animals are not simply passively pushed by the current; instead, they actively swim away from the current source. Tadpoles do not exhibit positive rheotaxis towards the source of the flow at any flow rate but as a group are randomly oriented. Treatment with cobalt chloride, a known blocker of superficial neuromast function, significantly reduces the tendency to move downstream, but does not alter the preference for the sides and bottom of the tank. Tadpoles' movements under flow are consistent with a model of locomotion based on a directed random walk.
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http://dx.doi.org/10.1242/jeb.055392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120219PMC
July 2011

Development of tectal connectivity across metamorphosis in the bullfrog (Rana catesbeiana).

Brain Behav Evol 2010 24;76(3-4):226-47. Epub 2011 Jan 24.

Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI, USA.

In the bullfrog (Rana catesbeiana), the process of metamorphosis culminates in the appearance of new visual and visuomotor behaviors reflective of the emergence of binocular vision and visually-guided prey capture behaviors as the animal transitions to life on land. Using several different neuroanatomical tracers, we examined the substrates that may underlie these behavioral changes by tracing the afferent and efferent connectivity of the midbrain optic tectum across metamorphic development. Intratectal, tectotoral, tectotegmental, tectobulbar, and tecto-thalamic tracts exhibit similar trajectories of neurobiotin fiber label across the developmental span from early larval tadpoles to adults. Developmental variability was apparent primarily in intensity and distribution of cell and puncta label in target nuclei. Combined injections of cholera toxin subunit β and Phaseolus vulgaris leucoagglutinin consistently label cell bodies, puncta, or fiber segments bilaterally in midbrain targets including the pretectal gray, laminar nucleus of the torus semicircularis, and the nucleus of the medial longitudinal fasciculus. Developmentally stable label was observed bilaterally in medullary targets including the medial vestibular nucleus, lateral vestibular nucleus, and reticular gray, and in forebrain targets including the posterior and ventromedial nuclei of the thalamus. The nucleus isthmi, cerebellum, lateral line nuclei, medial septum, ventral striatum, and medial pallium show more developmentally variable patterns of connectivity. Our results suggest that even during larval development, the optic tectum contains substrates for integration of visual with auditory, vestibular, and somatosensory cues, as well as for guidance of motivated behaviors.
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http://dx.doi.org/10.1159/000322550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202948PMC
May 2011

Spatial location influences vocal interactions in bullfrog choruses.

J Acoust Soc Am 2010 Apr;127(4):2664-77

Department of Psychology, Brown University, Providence, Rhode Island 02912, USA.

A multiple sensor array was employed to identify the spatial locations of all vocalizing male bullfrogs (Rana catesbeiana) in five natural choruses. Patterns of vocal activity collected with this array were compared with computer simulations of chorus activity. Bullfrogs were not randomly spaced within choruses, but tended to cluster into closely spaced groups of two to five vocalizing males. There were nonrandom, differing patterns of vocal interactions within clusters of closely spaced males and between different clusters. Bullfrogs located within the same cluster tended to overlap or alternate call notes with two or more other males in that cluster. These near-simultaneous calling bouts produced advertisement calls with more pronounced amplitude modulation than occurred in nonoverlapping notes or calls. Bullfrogs located in different clusters more often alternated entire calls or overlapped only small segments of their calls. They also tended to respond sequentially to calls of their farther neighbors compared to their nearer neighbors. Results of computational analyses showed that the observed patterns of vocal interactions were significantly different than expected based on random activity. The use of a multiple sensor array provides a richer view of the dynamics of choruses than available based on single microphone techniques.
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http://dx.doi.org/10.1121/1.3308468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865710PMC
April 2010

Developmental and regional patterns of GAP-43 immunoreactivity in a metamorphosing brain.

Brain Behav Evol 2008 21;71(4):247-62. Epub 2008 Apr 21.

Department of Psychology, Brown University, Providence, RI 02912, USA.

Growth-associated protein-43 is typically expressed at high levels in the nervous system during development. In adult animals, its expression is lower, but still observable in brain areas showing structural or functional plasticity. We examined patterns of GAP-43 immunoreactivity in the brain of the bullfrog, an animal whose nervous system undergoes considerable reorganization across metamorphic development and retains a strong capacity for plasticity in adulthood. Immunolabeling was mostly diffuse in hatchling tadpoles, but became progressively more discrete as larval development proceeded. In many brain areas, intensity of immunolabel peaked at metamorphic climax, the time of final transition from aquatic to semi-terrestrial life. Changes in intensity of GAP-43 expression in the medial vestibular nucleus, superior olivary nucleus, and torus semicircularis appeared correlated with stage-dependent functional changes in processing auditory stimuli. Immunolabeling in the Purkinje cell layer of the cerebellum and in the cerebellar nucleus was detectable at most developmental time points. Heavy immunolabel was present from early larval stages through the end of climax in the thalamus (ventromedial, anterior, posterior, central nuclei). Immunolabel in the tadpole telencephalon was observed around the lateral ventricles, and in the medial septum and ventral striatum. In postmetamorphic animals, immunoreactivity was confined mainly to the ventricular zones and immediately adjacent cell layers. GAP-43 expression was present in olfactory, auditory and optic cranial nerves throughout larval and postmetamorphic life. The continued expression of GAP-43 in brain nuclei and in cranial nerves throughout development and into adulthood reflects the high regenerative potential of the bullfrog's central nervous system.
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http://dx.doi.org/10.1159/000127045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257825PMC
July 2008