bluuebunny/crossref_metadata_2025 huggingface dataset:
Histopathologic correlates of otoneurologic manifestations following head trauma
Authors: Makishima Kazumi , Sobel Steven F. , Snow James B.
Published: September 2006

The clinical course of patients dying of head trauma and the physiologic evaluation of audition in guinea pigs subjected to several forms of head trauma are correlated with the histopathologic findings in the brains and temporal bones. In the patients there was wide spread hemorrhage, edema, disorganization and disruption of neural tissue. Loss of Purkinje cells and other neural elements was prominent. The temporal bone findings in the patients included laceration of and hemorrhage into the VHIth nerve as well as bleeding into the scala tympani. The membranous labyrinths demonstrated no specific changes secondary to the trauma. The guinea pigs developed a central form of hearing loss with elevated thresholds for evoked responses from the inferior colliculus and normal AC cochlear potentials. In the animals hemorrhage in the substance of the brain, necrosis of neural tissue, edema, disorganization and disruption were prominent. Although there was extravasation of blood in the tympanic and vestibular scalae, the membranous structures of the inner ears were well preserved.
Inner ear decompression sickness
Authors: Farmer Joseph C. , Thomas W. G. , Youngblood D. G. , Bennett P. B.
Published: September 2006

With recent increases in commercial, military, and sport diving to deeper depths, inner ear injuries during such exposures have been encountered more frequently and noted during several phases of diving: during compression, at stable deep depths, with excessive noise exposure in diving, and during decompression. The pathophysiology of these injuries differs, depending upon the phase of diving in which the injuries occur.

In this report, 23 cases of hearing loss, tinnitus, and/or vertigo occurring during or shortly after decompression are presented. Thirteen of these cases occurred in helium‐oxygen dives involving a change to air during the latter stages of decompression. A significant correlation is present between prompt recompression treatment, relief of symptoms, and lack of residual deficits.

Current knowledge indicates that the management of otologic decompression sickness should include: 1. prompt recompression to at least 99 feet deeper than the symptom onset depth; 2. recompression using the previous helium‐oxygen mixture when the injuries occur during or shortly after a switch from helium‐oxygen to air during the latter stages of decompression; 3. the use of parenteral diazepam for symptom relief and cyclic inhalations of oxygen enriched treatment gases; and 4. the avoidance of further diving by divers who exhibit permanent inner ear injuries after the acute symptoms have subsided.
Computer processing of audiological and vestibular data. II. A further note
Authors: Abel Sharon M. , Barber Hugh O.
Published: September 2006

This paper provides an addendum to an earlier paper describing the development of a computer record system for patient data. The specific problems addressed pertain to the storage and retrieval of historical information, physical signs and diagnosis. Some preliminary comparisons of audiological and vestibular test results are given for groups of patients with diagnoses of acoustic neuroma, Meniere's disease, temporal bone fracture and vestibular neuronitis.
Apnea and airway obstruction during feeding and sleep
Authors: Steinschneider Alfred , Rabuzzi Daniel D.
Published: September 2006

Recent awareness of the magnitude of sudden unexplained deaths in apparently healthy infants has lead to an increased interest in those circumstances that are associated with or can elicit prolonged and serious apneic episodes. In the present studies, attention was directed toward the study of physiologic activity during sleep and feeding.

Apneic episodes of varying durations occur during sleep which, in some instances, can be of sufficient length to warrant resuscitative intervention. A number of infants also reveal transient upper airway obstruction following brief periods of sleep apnea. This functional airway obstruction produces sudden and severe bradycardia. Similarly, infant feeding can induce dangerously prolonged periods of apnea and, in some infants, transient airway obstruction.

Few detailed studies have been performed to identify the anatomical level or characteristics of the obstruction. Available evidence suggests that this can take the form either of muscle hypotonicity or hypertonicity. Two infants observed by means of direct laryngoscopy revealed transient failure of vocal cord abduction. These results have provided for the development of two theoretical models that can result in the sudden infant death syndrome; furthermore, continuous recordings of respiratory and cardiac activity during feeding and sleep can be extremely valuable in elucidating the mechanisms responsible for the sudden development of apneic and cyanotic episodes in infants.
Pseudomonas meningitis complicating head and neck surgery
Authors: Bray David A. , Calcaterra Thomas C.
Published: September 2006

Three patients, each of whom had Pseudomonas meningitis as a sequela of an extensive head and neck operation, have been treated successfully. All three patients had cerebrospinal fluid leaks, and operative management of this complication is discussed. Antibiotic management included the parenteral administration of the recently developed drugs gentamicin, car‐benicillin, and intrathecal gentamicin. Since extensive head and neck operations are being performed with increasing frequency and since infectious complications are inevitable, it is mandatory that the otolaryngologist be familiar with current methods of managing these potentially lethal conditions.
The efficacy of “conservative” medical regimens on the rate of hearing losses in meniere's syndrome: A retrospective computerized statistical analysis
Authors: Weintraub Jonathan , Arenberg I. Kaufman , Spector Gershon J. , Stroud Malcolm H.
Published: September 2006

The records of 47 patients with Ménière's syndrome were analyzed in a retrospective computerized study to determine the effect of different medical regimens on the long term course of hearing loss. Four treatment groups, including histamine (subcutaneous), other vasodilators (oral), vitamins, and untreated controls were examined. Results suggest that there was no statistically significant difference among the four groups in the rates or absolute level of hearing loss or SRT despite different therapeutic regimens. The ability of these agents to conserve hearing in patients with Ménière's syndrome remains unproven on the basis of clinical and laboratory evidence.
An experimental model for the study of endolymphatic hydrops in sharks: Implications for the clinician
Authors: Arenberg I. Kaufman , Murray John P. , Rauchbach Erol , Schenck Nicholas L.
Published: September 2006

In recent years, attention has focused on the role of the endolymphatic sac (ELS) and the endolymphatic duct (ELD) in the pathogenesis of endolymphatic hydrops (ELH). Changes have been noted surgically and ra‐diographically by others in the ELS and ELD in patients with ELH.

This report summarizes the development of a shark model with which to study the pathophysiology of ELH. The background material and overall results of anatomic, histopathologic, and ultrastructural studies using the model are presented. Possible implications for the clinical handling of ELH as a result of this work is emphasized.
Division of posterior cricoid plate in young children with subglottic stenosis
Authors: Crysdale William S. , Platt L. J.
Published: September 2006

Subglott́ic stenosis was corrected surgically in three young children. The key surgical maneuver is the anterior and posterior division of the cricoid cartilage. Endoscopic, xerographic and speech assessments have been done at intervals since decannulation. The anterior commissure is widened and the endolarynx derformed in two children examined. Radio‐graphic studies indicated that increased airway diameters have been maintained to date. Speech has been adversely affected to some degree in all three patients.
Pharyngoesophageal dysphagia and gastroesophageal reflux
Authors: Henderson R. D. , Woolf C. , Marryatt G.
Published: September 2006

Pharyngoesophageal dysphagia occurred in 51.3 percent of 1,000 consecutive patients with gastroesophageal reflux. Aspiration, secondary to food obstruction, occurred in 30 percent of these patients, and some developed significant secondary respiratory symptoms.

The site of obstruction was localized to the cricopharyngeus by timing the interval from swallow to obstruction. Cricopharyngeal incoordination was demonstrated in 20 of 52 patients studied by high speed esophageal manometry.

Surgical correction of gastroesophageal reflux in patients with intractable reflux symptoms was shown to be effective in relieving pharyngoesophageal dysphagia in all but a small number of patients with very severe symptoms. In those with persistent dysphagia cricopharyngeal myotomy at a later stage was effective in giving relief.
Hemilaryngectomy for t3 (fixed cord) epidermoid carcinoma of larynx
Authors: Lesinski S. G. , Bauer W. C. , Ogura J. H.
Published: September 2006

This clinicopathologic study was undertaken to determine whether true vocal cord fixation produced by epidermoid carcinoma is an absolute con‐tra‐indication to treatment by hemilaryngectomy.

In a consecutive series of 114 hemilaryngectomies performed at McMillan Hospital (1960‐1967) for previously untreated epidermoid carcinoma, 18 patients had fixation of the involved true vocal cord. Each hemilaryngectomy specimen (serial step sections in the longitudinal plane) was re‐examined to ascertain the cause of vocal cord fixation; the adequacy of margin; and the presence of blood vessel, nerve sheath and cartilage invasion. Clinical follow‐up on each patient was current through December, 1972 (5‐12 years postop). All of these cases were seen initially by one of the authors (J. H. O.).

Serial sections revealed that true vocal cord fixation was caused by muscle invasion in 14 of the 18 patients. “Positive margins” were present in eight patients but no immediate treatment was given. Two of these patients developed biopsy proven local recurrences, and both were cured with Co“0 irradiation.

Among the 18 patients with T3 epidermoid carcinoma treated by hemilaryngectomy:

Three local recurrences developed, all in the anterior commissure. Two were cured with irradiation. The third had a laryngectomy but died from persistent cancer.

Two patients developed cervical metastases (without local recurrence), and one was salvaged with radical neck dissection.

Four patients died of other causes, cancer free, three to five years postoperatively.

Of the 14 determinant patients, two patients died of cancer. Twelve (85 percent) were alive and free of cancer five years postoperatively. Two had received full course irradiation; one had a radical neck dissection, and all 12 had a functioning larynx.

When Ogura's patients are added to the reports of other hemilaryngec‐tomies performed despite true vocal cord fixation (Leroux‐Robert [1950] 18/24, Kirchner, Som [1971] 13/19), a determinant salvage rate of 78 percent can be expected.

True vocal cord fixation is generally caused by invasion of the vocalis muscle and thus may be well encompassed by a hemilaryngectomy. The precise anatomical limits of the lesion should dictate the type of surgery required for cure.
Use of Modafinil for the Treatment of Attention Deficit/Hyperactivity Disorder
Authors: Lindsay Shane E , Gudelsky Gary A , Heaton Pamela C
Published: September 2006

Objective:

To review the evidence for the use of modafinil in the treatment of attention deficit/hyperactivity disorder (ADHD).

Data Sources:

A MEDLINE search (January 1990–May 2006) was conducted using MeSH terms ADHD and modafinil. The search was limited to English-language articles on clinical trials in humans. The Cochrane Database was also searched.

Study Selection and Data Extraction:

The literature search yielded 4 randomized clinical trials.

Data Synthesis:

The use of modafinil in the treatment of ADHD is associated with significant improvements in primary outcome measures used to assess the status of patients diagnosed with ADHD. Several aspects of cognitive function in ADHD patients also appear to improve following modafinil treatment. Modafinil shows a favorable adverse effect profile. Insomnia and headache were the most common adverse effects, seen in approximately 20% of treated individuals. However, it has not been demonstrated that the beneficial effects of modafinil are maintained with chronic administration.

Conclusions:

Modafinil may be a viable option for some patients in the treatment of ADHD, perhaps those for whom standard ADHD therapies have not been successful or tolerated. There remains a need for additional large, long-term studies using flexible titration methods to optimize the dose of modafinil to establish safety and efficacy, as well as head-to-head comparisons between modafinil and both long- and short-acting stimulants to determine the role of modafinil in the treatment of ADHD.
Whither the Garden Path? Some Gnomes Revisited and Some Others Worth Considering
Authors: Ewing Jan
Published: September 2006

In 1991 Dr Kevin Walsh, the founding President of ASSBI, presented an invited address entitled “Some gnomes worth knowing” in which he discussed examples of common errors and difficulties in neuropsychological test interpretation in the form of “gnomes” or aphorisms from prominent clinicians. His paper was aimed at demonstrating “the need for improvement in the education of all psychologists who are likely to be faced with essentially neuropsychological problems”. The current paper will examine the extent to which such improvement has occurred over the past eight years and will consider directions for the future. The major areas of concern outlined by Dr Walsh will be reviewed in terms of current clinical practice. Additional areas of controversy and concern which have emerged more recently, such as the assessment of mild head injury, the assessment of malingering and the impact of neurochemical changes in certain psychiatric conditions, will also be considered. The importance of considering the client in a more holistic manner, which takes into account a range of issues that may impact upon test scores, is emphasised. It is hoped that this presentation will assist in formulating more clearly the challenges facing all those involved in research, assessment and treatment of brain disorders as we approach a new millennium.
Stimulant Use in Paediatric Acquired: Brain Injury: Evaluation of a Protocol
Authors: Bakker Kathleen , Waugh Mary-Clare
Published: September 2006

Children with acquired brain injury (ABI) experience deficits in attentional skills such as, sustained attention, distractability and impulsivity, which have the potential to influence all aspects of their functioning. The use of central nervous system (CNS) stimulants is gaining increasing popularity in adult ABI literature. CNS stimulants have been successfully utilised in the management of attentional problems in attention deficit-hyperactivity disorder and are believed to have their therapeutic effect by modulating neurotransmitter function in the neocortex, an area of the brain implicated in the neurobehavioural sequelae of ABI. Research into the use of CNS stimulants in paediatric ABI reports contradictory findings. We present the case of LI a 7-year-old boy with a history of ABI who underwent a trial of stimulant medication for management of attentional deficits. The case is discussed with regard to the efficacy of the pharmacological intervention and the design of objective protocols for stimulant trials.
Traumatic Brain Injury Without Loss of Consciousness: A Case Study
Authors: Crowe Simon F.
Published: September 2006

Whilst many investigators concede that traumatic brain injury (TBI) without loss of consciousness (LOC) can occur, the number of times that this phenomena is reported in the literature is small. This case report presents an instance of TBI without LOC as supported by the observation of slowed processing speed, anosmia and a marked post-traumatic dysexecutive syndrome featuring moderately severe disinhibition. The case is discussed with a view to determining the mechanics of the blow necessary to both damage the cerebral substance yet maintain consciousness intact.
Problems and Pitfalls in the Assessment of Posttraumatic Amnesia
Authors: Tate Robyn L , Pfaff Anne
Published: September 2006

In the early stages of recovery after a traumatic brain injury, patients usually experience a period of posttraumatic amnesia (PTA) in which they are confused, amnesic for ongoing events, and frequently behaviourally agitated. Although a variety of procedures and instruments are available to measure the duration of PTA, their applications in clinical practice are far from ideal. This review paper describes retrospective and prospective measures of PTA and critically examines variations in item content and scoring procedures. In particular, methods currently available to measure the amnesia component of PTA are especially problematic. The limitations of PTA scales give rise to a number of difficulties that impact upon clinical practice. These include determining precisely when a patient has emerged from PTA, and distinguishing between patients in PTA and those with chronic amnesia. It is concluded that there is a need to revisit basic constructs comprising PTA, and develop an instrument with greater specificity. More focus should be placed on examining the confusional component of PTA, and validity of PTA tests would be improved by measuring attention and behaviour, in addition to orientation and memory.
Cognitive Flexibility in the Normal Elderly and in Persons with Dementia as Measured by the Written and Oral Trail Making Tests
Authors: Kowalczyk Agata , McDonald Skye , Cranney Jacquelyn , McMahon Michael
Published: September 2006

This study investigated cognitive flexibility as indexed by the Written and Oral Trail Making Test (TMT) in sixteen persons with dementia and 60 normal elderly. Written and Oral TMT performances were significantly correlated with each other and with other tests of cognitive flexibility providing an index of the convergent construct validity of these tests. Part B of the Written TMT was influenced by psychomotor ability although this was diminished by the use of a ratio score B/A rather than simply Part B performance. The Oral test was not related to visual or motor skills, providing evidence for its divergent validity. Both parts of the Written and Oral TMT were found to be sensitive to cognitive decline in dementia. Performance on both Oral and Written TMT was also influenced by age, gender, education and intellectual ability. Previous norms (e.g., MOANS) for the Written TMT which are based on relatively educated elderly, tended to provide deflated scores for the community group tested here. Some additional, preliminary normative data for both tests were compiled which take into account the influences of each of these variables.
ASSBI'S Founding President Reminisces
Authors: Walsh Kevin
Published: September 2006

On addressing our first meeting in 1976, I speculated on whether the study of the brain and behaviour which had flowered in the preceding decade would continue to develop and assist us in treating brain impaired individuals. Not only did this happen but our Society (Australian Society for the Study of Brain Impairment) founded two years later has gone from one good thing to another. My reservation in accepting the invitation to speak at this 23rd Annual Brain Impairment Conference was a concern about preaching to the converted. My life-time role has been that of missionary, both at home and abroad and, like teachers of all faiths, I have no reservations about repeating what are to me fundamental truths. I will try to keep to the theme of the emergence of ideas rather than an autobiography, but some chronology will help set the background.
The Role of G-Protein-Coupled Receptor Kinase 5 in Pathogenesis of Sporadic Parkinson's Disease
Authors: Arawaka Shigeki , Wada Manabu , Goto Saori , Karube Hiroki , Sakamoto Masahiro , Ren Chang-Hong , Koyama Shingo , Nagasawa Hikaru , Kimura Hideki , Kawanami Toru , Kurita Keiji , Tajima Katsushi , Daimon Makoto , Baba Masanori , Kido Takashi , Saino Sachiko , Goto Kaoru , Asao Hironobu , Kitanaka Chihumi , Takashita Emi , Hongo Seiji , Nakamura Takao , Kayama Takamasa , Suzuki Yoshihiro , Kobayashi Kazuo , Katagiri Tadashi , Kurokawa Katsuro , Kurimura Masayuki , Toyoshima Itaru , Niizato Kazuhiro , Tsuchiya Kuniaki , Iwatsubo Takeshi , Muramatsu Masaaki , Matsumine Hiroto , Kato Takeo
Published: September 2006

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of α-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with α-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of α-synuclein at the plasma membrane and induced translocation of phosphorylated α-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of α-synuclein. Genetic association study revealed haplotypic association of theGRK5gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of theGRK5gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of α-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.
α-Synuclein Overexpression Increases Cytosolic Catecholamine Concentration
Authors: Mosharov Eugene V. , Staal Roland G. W. , Bové Jordi , Prou Delphine , Hananiya Anthonia , Markov Dmitriy , Poulsen Nathan , Larsen Kristin E. , Moore Candace M. H. , Troyer Matthew D. , Edwards Robert H. , Przedborski Serge , Sulzer David
Published: September 2006

Dysregulation of dopamine homeostasis and elevation of the cytosolic level of the transmitter have been suggested to underlie the vulnerability of catecholaminergic neurons in Parkinson’s disease. Because several known mutations in α-synuclein or overexpression of the wild-type (WT) protein causes familial forms of Parkinson’s disease, we investigated possible links between α-synuclein pathogenesis and dopamine homeostasis. Chromaffin cells isolated from transgenic mice that overexpress A30P α-synuclein displayed significantly increased cytosolic catecholamine levels as measured by intracellular patch electrochemistry, whereas cells overexpressing the WT protein and those from knock-out animals were not different from controls. Likewise, catechol concentrations were higher inl-DOPA-treated PC12 cells overexpressing A30P or A53T compared with those expressing WT α-synuclein, although the ability of cells to maintain a low cytosolic dopamine level afterl-DOPA challenge was markedly inhibited by either protein. We also found that incubation with low-micromolar concentrations of WT, A30P, or A53T α-synuclein inhibited ATP-dependent maintenance of pH gradients in isolated chromaffin vesicles and that the WT protein was significantly less potent in inducing the proton leakage. In summary, we demonstrate that overexpression of different types of α-synuclein disrupts vesicular pH and leads to a marked increase in the levels of cytosolic catechol species, an effect that may in turn trigger cellular oxyradical damage. Although multiple molecular mechanisms may be responsible for the perturbation of cytosolic catecholamine homeostasis, this study provides critical evidence about how α-synuclein might exert its cytotoxicity and selectively damage catecholaminergic cells.
ΔFosB in the Nucleus Accumbens Regulates Food-Reinforced Instrumental Behavior and Motivation
Authors: Olausson Peter , Jentsch J. David , Tronson Natalie , Neve Rachel L. , Nestler Eric J. , Taylor Jane R.
Published: September 2006

Alterations in motivation have been implicated in the pathophysiology of several psychiatric disorders, including substance abuse and depression. Repeated exposure to drugs of abuse or stress is known to persistently induce the transcription factor ΔFosB in the nucleus accumbens (NAc) and dorsal striatum, effects hypothesized to contribute to neuroadaptations in dopamine-regulated signaling. Little is known, however, about the specific involvement of ΔFosB in dysregulation of appetitively motivated behaviors. We show here that inducible overexpression of ΔFosB in NAc and dorsal striatum of bitransgenic mice, or specifically in the NAc core of rats by use of viral-mediated gene transfer, enhanced food-reinforced instrumental performance and progressive ratio responding. Very similar behavioral effects were found after previous repeated exposure to cocaine, amphetamine, MDMA [(+)-3,4-methylenedioxymethamphetamine], or nicotine in rats. These results reveal the powerful regulation of motivational processes by ΔFosB, and provide evidence that drug-induced alterations in gene expression via induction of ΔFosB within the NAc core may play a critical role in the impact of motivational influences on instrumental behavior.
Photic Regulation of ArylalkylamineN-Acetyltransferase Binding to 14-3-3 Proteins in Retinal Photoreceptor Cells
Authors: Pozdeyev Nikita , Taylor Carla , Haque Rashidul , Chaurasia Shyam S. , Visser Amy , Thazyeen Aamera , Du Yuhong , Fu Haian , Weller Joan , Klein David C. , Iuvone P. Michael
Published: September 2006

14-3-3 proteins are a ubiquitous, highly conserved family of chaperone proteins involved in signal transduction, regulation of cell cycle, intracellular trafficking/targeting, cytoskeletal structure, and transcription. Although 14-3-3 proteins are among the most abundant proteins in the CNS, very little is known about their functional roles in the vertebrate retina. In the present study, we demonstrated that photoreceptors express 14-3-3 protein(s) and identified a 14-3-3 binding partner in photoreceptor cells, the melatonin-synthesizing enzyme arylalkylamineN-acetyltransferase (AANAT). Importantly, our data demonstrate that the binding of 14-3-3 to AANAT is regulated by light, with dramatic functional consequences. During the night in darkness, retinal AANAT is phosphorylated and forms a complex with 14-3-3 proteins with an apparent molecular weight of ∼90 kDa. Phosphorylation of AANAT facilitates the binding of enzyme to 14-3-3 proteins. Within the complex, AANAT is catalytically activated and protected from dephosphorylation and degradation. Light disrupts the AANAT/14-3-3 complex, leading to catalytic inactivation, dephosphorylation, and proteolytic degradation of the enzyme. In the presence of the proteasome inhibitor, lactacystin, light results in the formation of a high molecular weight complex (>150 kDa), which may represent an intermediate in the AANAT degradation process. These findings provide new insight into the roles of 14-3-3 proteins in photoreceptor cells and to the mechanisms controlling melatonin synthesis in the vertebrate retina.
Nonlinear Interaction between Shunting and Adaptation Controls a Switch between Integration and Coincidence Detection in Pyramidal Neurons
Authors: Prescott Steven A. , Ratté Stéphanie , De Koninck Yves , Sejnowski Terrence J.
Published: September 2006

The membrane conductance of a pyramidal neuronin vivois substantially increased by background synaptic input. Increased membrane conductance, or shunting, does not simply reduce neuronal excitability. Recordings from hippocampal pyramidal neurons using dynamic clamp revealed that adaptation caused complete cessation of spiking in the high conductance state, whereas repetitive spiking could persist despite adaptation in the low conductance state. This behavior was reproduced in a phase plane model and was explained by a shunting-induced increase in voltage threshold. The increase in threshold allows greater activation of the M current (IM) at subthreshold potentials and reduces the minimum adaptation required to stabilize the system; in contrast, activation of the afterhyperpolarization current is unaffected by the increase in threshold and therefore remains unable to stop repetitive spiking. The nonlinear interaction between shunting andIMhas other important consequences. First, timing of spikes elicited by brief stimuli is more precise when background spikes elicited by sustained input are prohibited, as occurs exclusively withIM-mediated adaptation in the high conductance state. Second, activation ofIMat subthreshold potentials, which is increased in the high conductance state, hyperpolarizes average membrane potential away from voltage threshold, allowing only large, rapid fluctuations to reach threshold and elicit spikes. These results suggest that the shift from a low to high conductance state in a pyramidal neuron is accompanied by a switch from encoding time-averaged input with firing rate to encoding transient inputs with precisely timed spikes, in effect, switching the operational mode from integration to coincidence detection.
Deciphering the Spike Train of a Sensory Neuron: Counts and Temporal Patterns in the Rat Whisker Pathway
Authors: Arabzadeh Ehsan , Panzeri Stefano , Diamond Mathew E.
Published: September 2006

Rats achieve remarkable texture discriminations by sweeping their facial whiskers along surfaces. This work explores how neurons at two levels of the sensory pathway, trigeminal ganglion and barrel cortex, carry information about such stimuli. We identified two biologically plausible coding mechanisms, spike counts and patterns, and used “mutual information” to quantify how reliably neurons in anesthetized rats reported texture when “decoded” according to these candidate mechanisms. For discriminations between surfaces of different coarseness, spike counts could be decoded reliably and rapidly (within 30 ms after stimulus onset in cortex). Information increased as responses were considered as spike patterns with progressively finer temporal precision. At highest temporal resolution (spike sequences across six bins of 4 ms), the quantity of “information” in patterns rose 150% for ganglion neurons and 110% for cortical neurons above that in spike counts. In some cases, patterns permitted discriminations not supported by spike counts alone.
The Effect of Lateral Septum Corticotropin-Releasing Factor Receptor 2 Activation on Anxiety Is Modulated by Stress
Authors: Henry Brook , Vale Wylie , Markou Athina
Published: September 2006

Corticotropin-releasing factor (CRF), a 41 amino acid peptide, mediates endocrine, autonomic, and behavioral responses to stress. Whereas the CRF1receptor appears to contribute to anxiety associated with stress, the role of the CRF2receptor remains unclear and may depend on drug dose, brain location, or testing environment. Results involving treatments with selective CRF2receptor agonists or antagonists and the behavior of CRF2receptor knock-out mice suggest both anxiogenic and anxiolytic effects of CRF2receptor activation. The present study tested the hypothesis that the effect of CRF2receptor activation on anxiety depends on the stress level of the animal. The selective CRF2receptor agonist urocortin 2 was infused into the lateral septum of mice under low- or high-stress (30 min of immobilization) testing conditions, and then behavior in the light–dark box, open-field, and novel-object tests was assessed. In the low-stress environment, 240 pmol of septal urocortin 2 increased anxiety, but lower doses (0.48, 4.8, and 48 pmol) did not have consistent effects. However, in the high-stress condition, 48 pmol of septal urocortin 2 significantly increased anxiety compared with control in wild-type but not CRF2receptor knock-out mice in the light–dark box. Septal administration of the relatively selective CRF2antagonist astressin-2B, but not the CRF1- selective antagonist antalarmin, blocked the anxiogenic effects of urocortin 2. Urocortin 2 infusion into the medial septum or lateral ventricle did not affect anxiety measures. These results indicate that the effect of septal CRF2receptor activation on anxiety is dependent on stress level.
The B′ Protein Phosphatase 2A Regulatory Subunitwell-roundedRegulates Synaptic Growth and Cytoskeletal Stability at theDrosophilaNeuromuscular Junction
Authors: Viquez Natasha M. , Li Caroline R. , Wairkar Yogesh P. , DiAntonio Aaron
Published: September 2006

Synaptic growth is essential for the development and plasticity of neural circuits. To identify molecular mechanisms regulating synaptic growth, we performed a gain-of-function screen for synapse morphology mutants at theDrosophilaneuromuscular junction (NMJ). We isolated a B′ regulatory subunit of protein phosphatase 2A (PP2A) that we have namedwell-rounded(wrd). Neuronal overexpression ofwrdleads to overgrowth of the synaptic terminal. Endogenous Wrd protein is present in the larval nervous system and muscle and is enriched at central and neuromuscular synapses.wrdis required for normal synaptic development; in its absence, there are fewer synaptic boutons and there is a decrease in synaptic strength.wrdfunctions presynaptically to promote normal synaptic growth and postsynaptically to maintain normal levels of evoked transmitter release. In the absence ofwrd, the presynaptic cytoskeleton is abnormal, with an increased proportion of unbundled microtubules. Reducing PP2A enzymatic activity also leads to an increase in unbundled microtubules, an effect enhanced by reducingwrdlevels. Hence,wrdpromotes the function of PP2A and is required for normal cytoskeletal organization, synaptic growth, and synaptic function at theDrosophilaNMJ.
Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors
Authors: Mojsilovic-Petrovic Jelena , Jeong Goo-Bo , Crocker Amanda , Arneja Amrita , David Samuel , Russell David , Kalb Robert G.
Published: September 2006

The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs). Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide dismutase 1; G59S p150glued) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.
Deletion of the GABAAReceptor α1 Subunit Increases Tonic GABAAReceptor Current: A Role for GABA Uptake Transporters
Authors: Ortinski Pavel I. , Turner Jill R. , Barberis Andrea , Motamedi Gholam , Yasuda Robert P. , Wolfe Barry B. , Kellar Kenneth J. , Vicini Stefano
Published: September 2006

The loss of more than half the number of GABAAreceptors yet lack of pronounced phenotype in mice lacking the gene for the GABAAα1 subunit is somewhat paradoxical. We explored the role of tonic GABAAreceptor-mediated current as a target of compensatory regulation in the α1 knock-out (−/−) mice. A 62% increase of tonic current was observed in the cerebellar granule cells (CGCs) of α1−/−compared with wild-type (+/+) mice along with a 67% increase of baseline current variance. Examination of whole-cell currents evoked by low concentrations of GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol suggested no upregulation of α6 and δ subunit-containing GABAAreceptors in the α1−/−, confirming previous biochemical studies. Single-channel current openings were on average 32% shorter in the α1−/−neurons. Single-channel conductance and frequency of opening were not different between genotypes. Tonic current induced by application of the GABA transporter GAT-1 blocker NO711 (1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride) was significantly larger in the α1−/−, suggesting an increase of ambient GABA concentration. Experiments done with a known concentration of extracellular GABA complemented by a series of biochemical experiments revealed a reduction of GAT activity in α1−/−without an identifiable reduction of GAT-1 or GAT-3 protein. We report increased tonic GABAAreceptor-mediated current in the α1−/−CGCs as a novel compensatory mechanism. Our data establish a role for GABA transporters as regulators of neuronal excitability in this and relevant models and examine other tonic conductance-regulating mechanisms responsible for the adaptive response of the cerebellar network to a deletion of a major synaptic GABAAreceptor subunit.
Cerebellar Contributions to Locomotor Adaptations during Splitbelt Treadmill Walking
Authors: Morton Susanne M. , Bastian Amy J.
Published: September 2006

Locomotor adaptability ranges from the simple and fast-acting to the complex and long-lasting and is a requirement for successful mobility in an unpredictable environment. Several neural structures, including the spinal cord, brainstem, cerebellum, and motor cortex, have been implicated in the control of various types of locomotor adaptation. However, it is not known which structures control which types of adaptation and the specific mechanisms by which the appropriate adjustments are made. Here, we used a splitbelt treadmill to test cerebellar contributions to two different forms of locomotor adaptation in humans. We found that cerebellar damage does not impair the ability to make reactive feedback-driven motor adaptations, but significantly disrupts predictive feedforward motor adaptations during splitbelt treadmill locomotion. Our results speak to two important aspects of locomotor control. First, we have demonstrated that different levels of locomotor adaptability are clearly dissociable. Second, the cerebellum seems to play an essential role in predictive but not reactive locomotor adjustments. We postulate that reactive adjustments may instead be predominantly controlled by lower neural centers, such as the spinal cord or brainstem.
Activation of P2Y1Nucleotide Receptors Induces Inhibition of the M-Type K+Current in Rat Hippocampal Pyramidal Neurons
Authors: Filippov Alexander K. , Choi Roy C. Y. , Simon Joseph , Barnard Eric A. , Brown David A.
Published: September 2006

We have shown previously that stimulation of heterologously expressed P2Y1nucleotide receptors inhibits M-type K+currents in sympathetic neurons. We now report that activation of endogenous P2Y1receptors induces inhibition of the M-current in rat CA1/CA3 hippocampal pyramidal cells in primary neuron cultures. The P2Y1agonist adenosine 5′-[β-thio]diphosphate trilithium salt (ADPβS) inhibited M-current by up to 52% with an IC50of 84 nm. The hydrolyzable agonist ADP (10 μm) produced 32% inhibition, whereas the metabotropic glutamate receptor 1/5 agonist DHPG [(S)-3,5-dihydroxyphenylglycine] (10 μm) inhibited M-current by 44%. The M-channel blocker XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride] produced 73% inhibition at 3 μm; neither ADPβS nor ADP produced additional inhibition in the presence of XE991. The effect of ADPβS was prevented by a specific P2Y1antagonist, MRS 2179 (2′-deoxy-N′-methyladenosine-3′,5′-bisphosphate tetra-ammonium salt) (30 μm). Inhibition of the M-current by ADPβS was accompanied by increased neuronal firing in response to injected current pulses. The neurons responding to ADPβS were judged to be pyramidal cells on the basis of (1) morphology, (2) firing characteristics, and (3) their distinctive staining for the pyramidal cell marker neurogranin. Strong immunostaining for P2Y1receptors was shown in most cells in these cultures: 74% of the cells were positive for both P2Y1and neurogranin, whereas 16% were only P2Y1positive. These results show the presence of functional M-current-inhibitory P2Y1receptors on hippocampal pyramidal neurons, as predicted from their effects when expressed in sympathetic neurons. However, the mechanism of inhibition in the two cell types seems to differ because, unlike nucleotide-mediated M-current inhibition in sympathetic neurons, that in hippocampal neurons did not appear to result from raised intracellular calcium
Abnormal Positioning of Diencephalic Cell Types in Neocortical Tissue in the Dorsal Telencephalon of Mice Lacking Functional Gli3
Authors: Fotaki Vassiliki , Yu Tian , Zaki Paulette A. , Mason John O. , Price David J.
Published: September 2006

The transcription factor Gli3 (glioma-associated oncogene homolog) is essential for normal development of the mammalian forebrain. One extreme requirement for Gli3 is at the dorsomedial telencephalon, which does not form inGli3Xt/Xtmutant mice lacking functional Gli3. In this study, we analyzed expression of Gli3 in the wild-type telencephalon and observed ahighdorsal-to-lowventral gradient ofGli3expression and predominance of the cleaved form of the Gli3 protein dorsally. This graded expression correlates with theseveredorsal-to-mildventral telencephalic phenotype observed inGli3Xt/Xtmice. We characterized the abnormal joining of the telencephalon to the diencephalon and defined the medial limit of the dorsal telencephalon inGli3Xt/Xtmice early in corticogenesis. Based on this analysis, we concluded that some of the abnormal expression of ventral telencephalic markers previously described as being in the dorsal telencephalon is, in fact, expression in adjacent diencephalic tissue, which expresses many of the same genes that mark the ventral telencephalon. We observed occasional cells with diencephalic character in the Foxg1 (forkhead box)-expressingGli3Xt/Xttelencephalon at embryonic day 10.5, a day after the anatomical subdivision of the forebrain vesicle. Large clusters of such cells appear in theGli3Xt/Xtneocortical region at later ages, when the neocortex becomes highly disorganized, forming rosettes comprising mainly neural progenitors. We propose that Gli3 is indispensable for formation of an intact telencephalic–diencephalic boundary and for preventing the abnormal positioning of diencephalic cells in the dorsal telencephalon.
Effects of Variable Prey and Cohort Dynamics on Growth of Young‐of‐the‐Year Estuarine Bluefish: Evidence for Interactions between Spring‐ and Summer‐Spawned Cohorts
Authors: Scharf Frederick S. , Buckel Jeffrey A. , Rose Kenneth A. , Juanes Francis , Cowan James H.
Published: September 2006

Previous field studies of bluefish Pomatomus saltatrix have documented variation in young‐of‐the‐year (age‐0) growth rates among years and between spring‐ and summer‐spawned cohorts. However, the potential factors responsible for generating variable growth in age‐0 bluefish have not been investigated. We constructed an individual‐based model that combined size‐dependent bluefish foraging with a bioenergetics model to quantify the potential effects of variable prey fish dynamics on first‐summer growth of juvenile bluefish. We used long‐term monitoring data to define baseline conditions and calibrate the model. We then performed three simulation experiments designed to assess the effects of initial density and arrival timing of prey species and bluefish cohorts on bluefish length distributions on October 1. Simulation experiments indicated that spring‐spawned bluefish were robust to fluctuations in prey dynamics because of a spawning strategy that ensures temporal overlap with a diversity of prey fish species. In contrast, summer‐spawned bluefish were sensitive to variation in prey fish dynamics because of their dependence on a single prey species. Model results also revealed the potential for the time of arrival and the initial density of the spring‐spawned cohort to affect the growth of the summer‐spawned cohort. Our findings demonstrate that population‐level interactions between bluefish and their prey can be complex and have a considerable influence on the early growth rates of the summer‐spawned cohort.
Difference in Channel Catfish Growth among Mississippi Stream Basins
Authors: Shephard Samuel , Jackson Donald C.
Published: September 2006

We investigated basin‐scale factors that were likely to influence the growth of channel catfish Ictalurus punctatus in Mississippi floodplain rivers. Channel catfish were collected from nine streams during 2001–2002. All fish were measured (total length; mm) and aged from pectoral spine sections. Linear growth models were fitted to mean back‐calculated length‐at‐age data for channel catfish from each stream and were compared among streams. Channel catfish growth rate differed among streams. Multiple linear regression was used to correlate growth rate to basin‐scale environmental variables. The growth rate for channel catfish was related positively to soil fertility and negatively to altitude and percentage of the watershed comprising bottomland hardwood forest. Basin‐scale determination of environmental features related to channel catfish growth can assist managers and fisheries administrators with establishment of realistic expectations for riverine channel catfish fisheries at a scale that is administratively feasible and functionally defensible.
Native and Introduced Populations of Smallmouth Bass Differ in Concordance between Climate and Somatic Growth
Authors: Dunlop Erin S. , Shuter Brian J.
Published: September 2006

We characterized the association between climate and somatic growth in 125 North American populations of smallmouth bassMicropterus dolomieu. Using multivariate techniques (i.e., principal components and Procrustes analyses), we found an overall significant concordance between eight climate variables (cloud cover, frost frequency, precipitation, mean air temperature, minimum air temperature, maximum air temperature, mean summer air temperature, and growing degree‐days above 10°C) and four growth variables (body length increments for ages 1–4). Bivariate linear regressions revealed that there was a significant positive relationship between air temperature variables and early growth, while growth at later ages was generally less influenced by climate. Given that the geographical range of smallmouth bass has been rapidly expanding over the past century, we also examined how the climate–growth relationships differed in populations that have been introduced outside the native distribution. Analysis of residuals from the Procrustes test indicated that the concordance between climate and growth was probably higher for populations within the native range and lower for introduced populations. Mechanisms that might generate this pattern include the possibilities that (1) the introduced populations have not had time to adapt to their new environments and (2) growth might respond atypically to the more extreme climates experienced outside the native range of the species.