Rostrocaudal Length Research Articles

Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5’-AMP-activated protein kinase activity and transmitter marker protein expression

BackgroundThe oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons. MethodsNitric oxide synthase (nNOS)- or glutamate decarboxylase65/67 (GAD)-immunoreactive neurons were laser-catapult-microdissected from male and female rat VMN after subcutaneous insulin injection and caudal fourth ventricular L-lactate or vehicle infusion for Western blot protein analysis. ResultsHindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron nNOS expression, and prevented up-regulation of phosphorylated AMPK 5’-AMP-activated protein kinase (pAMPK) expression in those neurons. Hypoglycemic suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN. ConclusionsResults document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN neurotransmitters in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.

Comparison of the retrosplenial cortex size between the degu (Octodon degus) and the Wistar rat (Rattus norvegicus).

The degu (Octodon degus) is a rodent that normally constructs burrows for nesting and rearing. To navigate inside these burrows, degus may use idiothetic and/or sensory cues more than visual information, which is less effective in burrows. Spatial information for navigation is processed in several key brain regions including the retrosplenial cortex (RS). However, the structural characteristics of the degu RS have not been previously reported. The present study measured the sizes of the RS and constituent areas 29 and 30 in the degu, and compared these to those found in the rat, which is a terrestrial rodent. The proportion of the rostrocaudal length of the entire RS relative to that of the entire cortex was significantly larger in degus versus rats. The proportion of the rostrocaudal length of the RS at levels rostral to the splenium of the corpus callosum relative to that of the entire cortex was also significantly larger in degus versus rats. Furthermore, the ratio of the estimated volume of area 29 relative to that of area 30 was significantly larger in degus versus rats. These results show that the degu has a rostrocaudally longer rostral RS with a larger area 29 compared to the rat, which suggests that these structural features may be relevant to differences in spatial information processing between the fossorial degu and terrestrial rat.

Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5'-AMP-activated protein kinase activity.

Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RIIH). Ventromedial hypothalamic nucleus (VMN) GABAergic neurons express the sensitive energy gauge 5′-AMP-activated protein kinase (AMPK). Current research used high-neuroanatomical resolution single-cell microdissection tools to address the premise that GABAergic cells in the VMNvl, the primary location of ‘glucose-excited’ metabolic-sensory neurons in the VMN, exhibit attenuated sensor activation during RIIH. Data show that during acute hypoglycemia, VMNvl glutamate decarboxylase65/67 (GAD)-immunoreactive neurons maintain energy stability, yet a regional subset of this population exhibited decreased GAD content. GABA neurons located along the rostrocaudal length of the VMNvl acclimated to RIIH through a shift to negative energy imbalance, e.g. increased phosphoAMPK expression, alongside amplification/gain of inhibition of GAD profiles. Acquisition of negative GAD sensitivity may involve altered cellular receptivity to noradrenergic input via α2-AR and/or β1-AR. Suppression of VMNvl GABA nerve cell signaling during RIIH may differentiate this neuroanatomical population from other, possibly non-metabolic-sensory GABA neurons in the MBH. Data here also provide novel evidence that VMNvl GABA neurons are direct targets of glucocorticoid control, and show that glucocorticoid receptors may inhibit RIIH-associated GAD expression in rostral VMNvl GABAergic cells through AMPK-independent mechanisms.

Influência do ambiente na estrutura de tamanho e biomassa da Emerita brasiliensis (Schimitt, 1935) na praia Brava e Guarda do Embaú

Emerita brasiliensis is an important species of Brazilian macrofauna, they are inhabitants of the intertidal areas, and have important components that enable their use as biological indicators environmental. Therefore, the objective was to analyze the relationship between population and size of individuals of Eremita brasiliensis, comparing two beaches on the coast of Santa Catarina, being Praia brava in Itajaí, with an increasing level of urbanization and Guarda do Embaú Beach in Paulo Lopes, which has a stationary degree. The collections took place in March and September 2016, with the sample area parallel to the sand and intertidal strips for a systematic sampling observing the estimated time for low tide. For collection, a 20cm diameter PVC cylinder was used and buried at a depth of 20cm. The samples were arranged in a 0.5mm opening mesh and sent to the laboratory, where the organisms of the genus Emerita brasiliensis were separated and identified for the measurement of biomorphometric data, observing the lateral diameter and rostro-caudal length of the carapace. The biomass weighing was performed before and after the drying procedure, performed in a controlled temperature oven at 37ºC for 48 hours. For statistical analysis, the ANOVA test was used. Based on the individuals collected, it is observed Guarda do Embaú beach with more individuals when compared to Brava Beach. Statistical data show a significant difference between the months and the beaches, which is justified by the state of conservation of Guarda do Embaú beach, which remains static due to its low urbanization. Therefore, it is concluded that the difference between Emerita Brasiliensis communities is due to changes in local dynamics, such as anthropic trampling and sediment change. The results were not accurate due to the low number of samples, but are significant and relevant for further research.

A visual lamina in the medulla oblongata of the frog, Rana pipiens

We have discovered a lamina of visually responsive units in the medulla oblongata of the frog. It spans the entire medial aspect of the rostrocaudal length of the medulla and extends dorsoventrally from the cell-dense dorsal zone into the cell-sparse ventral zone. Most visual units within this lamina have large receptive fields, with the majority extending bilaterally in the frontal visual field. Most of these neurons are binocular, have no apparent directional preference, respond equally well to stimuli of a variety of shapes and sizes, and exhibit strong habituation. More medial locations in the visual lamina represent ipsilateral visual space while more lateral locations within the lamina represent contralateral visual space. Many units in the caudal aspect of the visual lamina are bimodal, responding to both visual and somatosensory stimuli. HRP tracing reveals inputs to the lamina from many primary and secondary visual areas in the midbrain and diencephalon. There is no area-by-area segregation of the projections to the visual lamina. For example, most parts of the tectum project across the visual lamina. The only spatial order in the visual lamina is that at more medial sites there tends to be more input from contralateral tectum; and at more lateral sites there tends to be more input from ipsilateral tectum. There is bilateral input to the visual lamina from tectum, tegmentum, posterior nucleus of the thalamus, posterior tuberculum, and ventromedial thalamic nucleus. There is ipsilateral input to the visual lamina from torus semicircularis, pretectum, nucleus of Bellonci, and ventrolateral thalamic nucleus. There is contralateral input to the visual lamina from basal optic complex. Collectively, these results show the presence of visual influences in regions of the medulla that likely represent an important step in sensorimotor transformation.

Cytoarchitecture and myeloarchitecture of the entorhinal cortex of the common marmoset monkey (Callithrix jacchus).

The entorhinal cortex (EC) is associated with impaired cognitive function such as in the case of Alzheimer's disease, Parkinson's disease and Huntington's disease. The present study provides a detailed analysis of the cytoarchitectural and myeloarchitectural organization of the EC in the common marmoset Callithrix jacchus. Data were collected using Nissl and fiber stained preparations, supplemented with acetylcholinesterase and parvalbumin immunohistochemistry. The EC layers and subfields in the marmoset seem to be architectonically similar to those that have been proposed in nonhuman primates and humans to date; however, slight differences could be revealed using the present techniques. Throughout its rostrocaudal length, the entorhinal cortex presents a clear six-layered pattern. The entorhinal cortex is divided into six fields, named mainly in accordance to their rostrocaudal and mediolateral positions. At rostral levels, the neurons tend to be organized in patches that are surrounded by large, thick, radially oriented bundles of fibers, and the deep layers are poorly developed. At caudal levels, the divisions are more laminated in appearance. AChE staining at the borders of adjacent fields are consistent with the changes in layering revealed in Nissl-stained sections, of which the lateral regions of the EC display denser AChE staining than that of the medial banks. PV immunoreactivity was found in the labeled somata, dendrites, and axons in all layers and subdivisions. Additionally, we distinguished three subtypes of PV-immunoreactive neurons: multipolar, bipolar and spherical-shaped neurons, based on the shape of the somata and the disposition of the dendrites.

Bioenergy with Carbon Capture and Sequestration (BECCS): The Distracting Injustice of an Infeasible and Unlikely Technofix

The retinotectal projections from double-nasal (NN), double-temporal (TT) and double-ventral (VV) compound eyes in Xenopus were studied autoradiographically and electrophysiologically during development. Early TT projections were confined to rostrolateral tectum and spread with advancing age to cover most of the tectum by shortly after metamorphosis. Early VV projections showed a decreased density of label on lateral tectum. Early NN projections appeared to extend across the entire rostrocaudal length of the available tectum at all stages of development, but showed a decrease in label density on rostral tectum. The results are discussed in relation to various hypotheses about the formation of retinotectal connexions.

In vivo MRI assessment of the human locus coeruleus along its rostrocaudal extent in young and older adults

The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from low spatial resolution along the rostrocaudal axis of the LC rendering it difficult to differentiate its integrity in caudal and rostral portions. This study presents a novel approach to investigate the human LC in vivo using T1-weighted Fast Low Angle Shot (FLASH) MRI at 3 T (T). Using high-resolution isotropic imaging to minimise the effect of low spatial resolution in the slice direction, this study aimed to characterise the rostrocaudal distribution of LC signal intensity attributed to neuromelanin from 25 young (22–30) and 57 older (61–80) adults. We found a significant age-related increase in maximum but not median signal intensity, indicating age-related differences were not homogenous. Instead, they were confined to the rostral third of the LC with relative sparing of the caudal portion. The findings presented demonstrate in vivo T1-weighted FLASH imaging may be used to characterise signal intensity changes across the entire rostrocaudal length of the LC (a corresponding standardised LC map is available for download), which may help to identify how the human LC is differentially affected in aging and neurodegenerative disease.

Immunohistochemical Localization of Neuropeptide Arginine Vasopressin and Morphometric Study of Domestic Cat Amygdala

Neuropeptide arginine vasopressin (AVP) is known to modulate social behavior in several species. The AVP and its receptors are broadly distributed in the limbic system, with several studies documenting their involvement in behavior regulation. However, the role of AVP in feline behavior is unknown, due to lack of studies and possible species differences. Here, as the first step, we investigated the presence of AVP in the domestic cat amygdala by using immunohistochemistry on freely‐floating brain tissue sections. The amygdala is an important component of the circuitry underlying social behavior and emotions. Therefore, we also characterized the neuronal morphology of domestic cat amygdala using cresyl violet stained 30μm serial sections. Our results show the presence of AVP immunoreactive neurons in the domestic cat amygdala (4 males, 1 female). The average neuronal diameter was 10.7±0.3μm in the lateral nucleus, 14.2±0.6μm in the medial nucleus, 11.1±0.8μm in the central nucleus, and 14.3±1.4μm in the basal nucleus, within the amygdala. The rostrocaudal length of the amygdala ranged from 6.7 – 7.3mm (3 males, 1 female). Variations in neuronal diameters did not translate to AVP immunoreactivity. This study is the first demonstration of the presence of neuropeptide AVP in the domestic cat amygdala. This might suggest a potential role of AVP in regulating social behavior in domestic cats. The morphometric findings of neuronal diameter might complement the physiological findings, implementing different roles in behavior for different subnuclei. Such studies will lay foundation for future research in feline behavior to improve feline health and welfare.Support or Funding InformationWestern University of Health Sciences, Pomona, CA

Magnetic Resonance Imaging and Anatomical Correlation of Human Temporal Lobe Landmarks, in 3D Euclidean Space: A Study of Control and Alzheimer's Disease Subjects.

The medial temporal lobe (MTL), and in particular the hippocampal formation, is essential in the processing and consolidation of declarative memory. The 3D environment of the anatomical structures contained in the MTL is an important issue. Our aim was to explore the spatial relationship of the anatomical structures of the MTL and changes in aging and/or Alzheimer's disease (AD). MTL anatomical landmarks are identified and registered to create a 3D network. The brain network is quantitatively described as a plane, rostrocaudally-oriented, and presenting Euclidean/real distances. Correspondence between 1.5T RM, 3T RM, and histological sections were assessed to determine the most important recognizable changes in AD, based on statistical significance. In both 1.5T and 3T RM images and histology, inter-rater reliability was high. Sex and hemisphere had no influence on network pattern. Minor changes were found in relation to aging. Distances from the temporal pole to the dentate gyrus showed the most significant differences when comparing control and AD groups. The best discriminative distance between control and AD cases was found in the temporal pole/dentate gyrus rostrocaudal length in histological sections. Moreover, more distances between landmarks were required to obtain 100% discrimination between control (divided into <65 years or >65 years) and AD cases. Changes in the distance between MTL anatomical landmarks can successfully be detected by using measurements of 3D network patterns in control and AD cases.

Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome.

Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2+/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2+/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2+/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2+/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS.

気管切開下陽圧換気導入後の筋萎縮性側索硬化症患者の安静時唾液分泌量

Patients with amyotrophic lateral sclerosis (ALS) often suffer from salivation problems such as drooling and dry mouth. We examined resting salivation rate cross-sectionally in 66 advanced ALS patients with tracheostomy invasive ventilation using a cotton roll method, and investigated clinical factors associated with salivation rate. Resting salivation rate in the patients was well preserved (median value 0.6 g/min), and was significantly more increased in patients with impairment of jaw movement (P = 0.007) or mouth opening (P = 0.003) than in patients with less impairment, and in patients with the mouth being constantly open ≥ 10 mm in rostrocaudal length than in patients with < 10 mm. These data indicate that salivation rate was increased with progression of dysfunction of voluntary jaw movement. Appropriate oral care is required in advanced ALS patients to maintain their oral hygiene and to avoid penetration of saliva into the airway.

Estrogen-negative feedback and estrous cyclicity are critically dependent upon estrogen receptor-α expression in the arcuate nucleus of adult female mice.

The location and characteristics of cells within the brain that suppress GnRH neuron activity to contribute to the estrogen-negative feedback mechanism are poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP recombination in estrogen receptor-α (ERα) floxed mice (ERα(flox/flox)), we aimed to examine the role of ERα-expressing neurons located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism. Bilateral injection of AAV-Cre into the ARN of ERα(flox/flox) mice (n = 14) resulted in the time-dependent ablation of up to 99% of ERα-immunoreactive cell numbers throughout the rostrocaudal length of the ARN. These mice were all acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous. Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight was not altered in ERα(flox/flox) mice. After ovariectomy, a significant increment in LH secretion was observed in all genotypes, although its magnitude was reduced in ERα(flox/flox) mice. Acute and chronic estrogen-negative feedback were assessed by administering 17β-estradiol to mice as a bolus (LH measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later). This demonstrated that chronic estrogen feedback was absent in ERα(flox/flox) mice, whereas the acute feedback was normal. These results reveal a critical role for ERα-expressing cells within the ARN in both estrous cyclicity and the chronic estrogen negative feedback mechanism in female mice. This suggests that ARN cells provide a key indirect, transsynpatic route through which estradiol suppresses the activity of GnRH neurons.

A neuroanatomical and neurochemical study of the indusium griseum and anterior hippocampal continuation: Comparison with dentate gyrus

The indusium griseum (IG) and anterior hippocampal continuation (AHC) are longitudinal and continuous structures that consist of two narrow strips of gray matter overlying the rostrocaudal length of the corpus callosum, extending rostrally to the genu of the corpus callosum and ventrally to the rostrum. The present study aimed to characterize the phenotype of neuronal innervations to the IG-AHC and their intra-structural topographic organization.Using immunohistochemistry, we found nerve fibers expressing choline acetyltransferase, tyrosine hydroxylase, dopamine-β-hydroxylase, the serotonin reuptake transporter as well as glutamic acid decarboxylase-67 and parvalbumin. These suggest that the IG and AHC are innervated by acetylcholine, dopamine, noradrenaline, 5-hydroxytryptamine and GABA neurons. More importantly, all these fibers display a topographic laminar distribution in both brain areas. The presence of varicosities along the nerve fibers suggests that these neurotransmitters are released extracellullarly to exert a physiological action. Finally, the structural similarities with the dentate gyrus support the idea that the IG and AHC are anatomically associated, if not continuous, with this area and may represent in mammals a vestige of the hippocampus.

Management of isolated syringomyelia in the paediatric population – a review of imaging and follow-up in a single centre

Objective. To assess the natural history of isolated syringomyelia in children. Methods. MRI reports from February 2007 to August 2011 mentioning syrinx were identified on Sheffield Children's PACS database. Scans with syringes having an AP diameter of > 1 mm and extending over at least two vertebral bodies were reviewed. Patients with an identifiable cause such as a Chiari malformation were then excluded. Results. Thirty-nine patients were included with a mean age at diagnosis of 10.6 years. The average syrinx AP diameter was 3.30 mm. The rostrocaudal length of the syringes varied between 2 and 19 vertebral bodies. Twenty-seven out of 39 syringes were thoracic in origin. There were 3 and 6 syringes involving the cervicothoracic and thoracolumbar regions, respectively, with 3 involving the cervical area only. Eleven out of 39 (Group I) patients were found “incidentally” during work-up for adolescent idiopathic scoliosis and these were considered as a separate group. These patients did not have any significant symptoms and were discharged following their scoliosis correction surgery. Syrinx was incidental in 14 further patients (Group II). Of the 14 patients, 11 remained asymptomatic with no change in syrinx morphology throughout follow up. Of the 14 patients, 3 were lost to follow-up. Of the 39 patients, 14 (Group III) presented with progressive back pain without any obvious clinical cause. Of the 14, 10 either improved or remained the same. Of the14 patients, 3 underwent lumbar puncture, 1/14 having myelography. All 4/14 patients reported significant pain reduction on follow up following intervention. Conclusion. Idiopathic syrinx is a benign pathology, which can be managed expectantly. Most cases remain stable or improve over time. In a small minority who have progressive back pain, we have found that lumbar puncture may be helpful in reducing symptoms.

Analyzing Taphonomic Deformation of Ankylosaur Skulls Using Retrodeformation and Finite Element Analysis

Taphonomic deformation can make the interpretation of vertebrate fossil morphology difficult. The effects of taphonomic deformation are investigated in two ankylosaurid dinosaur taxa, Euoplocephalus tutus (to investigate effects on our understanding of intraspecific variation) and Minotaurasaurus ramachandrani (to investigate the validity of this genus). The ratio of orbit maximum rostrocaudal length to perpendicular height is used as a strain ellipse, which can be used to determine if ankylosaur skull fossils have been dorsoventrally compacted during fossilization and diagenesis. The software program Geomagic is used to retrodeform three-dimensional (3D) digital models of the ankylosaur skulls. The effects of sediment compaction are modeled using finite element analysis, and the resulting strain distributions are compared with the retrodeformed models as a test of the retrodeformation method. Taphonomic deformation can account for a large amount of intraspecific variation in Euoplocephalus, but finite element analysis and retrodeformation of Minotaurasaurus shows that many of its diagnostic features are unlikely to result from deformation.

Three-dimensional airway evaluation in 387 subjects from one university orthodontic clinic using cone beam computed tomography

To determine the linear, volumetric, and cross-sectional area measurements in a large sample of subjects seeking treatment in a university clinic of orthodontics. Cone-beam computed tomography (CBCT) scans from 387 patients were analyzed retrospectively. All scans were loaded into the 3dMDvultus program (Atlanta, Ga) for airway analysis using automated segmentation. Gender, age, height, weight, airway length, volume, and area of maximum constriction were collected. The rostrocaudal length of the airway increased with age until the age of 15 years in female subjects but continued to increase in male subjects and ranged from 44 to 88 mm over the period of 8 to 18 years of age with the gender data combined. The volume of the airway increased through the entire 11-year age range from 2000 mm(3) to 27,000 mm(3). The rate of airway volume increased at a slower rate in female than in male subjects. The smallest cross-sectional area increased with age ranging from 20 to 250 mm(2) but at a slower rate with female subjects, while male subjects demonstrated a more exponential increase after the age of 13 years. The human airway increases in length and volume during a rapid period of craniofacial growth in patients between the ages of 8 and 18 years, and the site of maximum cross-sectional area constriction can vary.

A mouse model for adolescent alcohol abuse: stunted growth and effects in brain.

Adolescent alcohol abuse remains a serious public health concern, with nearly a third of high school seniors reporting heavy drinking in the previous month. Using the high ethanol-consuming C57BL/6J mouse strain, we examined the effects of ethanol (3.75g/kg, IP, daily for 45days) on body weight and brain region mass (cerebral cortex, cerebellum, corpus callosum) during peri-adolescence (postnatal day [P]25 to 70) or adulthood (P180 to 225) of both males and females. In control peri-adolescent animals, body weight gain was greater in males compared with females. In the peri-adolescent exposure group, ethanol significantly reduced body weight gain to a similar extent in both male and female mice (82 and 84% of controls, respectively). In adult animals, body weight gain was much less than that of the peri-adolescent mice, with ethanol having a small but significant effect in males but not females. Between the control peri-adolescent and adult cohorts (measurements taken at P70 and 225, respectively), there were no significant differences in the mass of the cerebral cortex or the cerebellum from either male or female mice, although the rostro-caudal length of the corpus callosum increased slightly but significantly (6.1%) between these time points. Ethanol treatment significantly reduced the mass of the cerebral cortex in peri-adolescent (-3.1%), but not adult, treated mice. By contrast, ethanol significantly reduced the length of the corpus callosum in adult (-5.4%), but not peri-adolescent, treated mice. Future studies at the histological level may yield additional details concerning ethanol and the peri-adolescent brain.

Adverse effects of serotonin depletion in developing zebrafish

In this study, p-chlorophenylalanine (pCPA), an inhibitor of tryptophan hydroxylase (the rate limiting enzyme of serotonin synthesis), was used to reduce serotonin (5HT) levels during early development in zebrafish embryos. One day old dechorionated embryos were treated with 25μM pCPA for 24h and subsequently rescued. Immunohistological studies using a 5HT antibody confirmed that 5HT neurons in the brain and spinal cord were depleted of transmitter by 2days post fertilization (dpf). Twenty four hours after pCPA exposure embryos were unable to burst swim and were nearly paralyzed. Movement began to improve at 4dpf, and by 7dpf, larvae exhibited swimming activity. Rescued larvae continued to grow in rostrocaudal length over 5days post-rescue, but their length was always 16–21% below controls. Surprisingly, both groups displayed the same number of myotomes. To examine whether hypertonicity of myotomes in treated embryos played a role in their shorter rostrocaudal lengths, 1dpf embryos were exposed to a combination of 25μM pCPA and 0.6mM of the sodium channel blocker ethyl 3-aminobenzoate methanesulfonate (MS-222). After a 24hour exposure, the embryos exhibited the same rostrocaudal length as control embryos suggesting that myotome hypertonicity plays a major role in the decreased axial length of the treated larvae. In addition, pCPA treated 2dpf embryos exhibited abnormal notochordal morphology that persisted throughout recovery. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the relative levels of the serotonin 1A receptor (5HT1A) transcript and the serotonin transporter (SERT) transcript in the brain and spinal cord of control and treated embryos. Transcripts were present in both brain and spinal cord as early as 1dpf and reached maximal concentrations by 3dpf. Embryos treated with pCPA demonstrated a decrease in the concentration of 5HT1A transcript in both brain and spinal cord. While SERT transcript levels remained unaffected in brain, they were decreased in spinal cord. Five days subsequent to pCPA rescue, 5HT1A transcript concentrations remained decreased in brain while SERT transcript levels were elevated in both regions. These findings suggest that reduction of 5HT during early zebrafish development may have an adverse effect on body length, notochordal morphology, locomotor behavior, and serotonin message-related expression.

Inter- and Intrapatient Variability of Facial Nerve Response Areas in the Floor of the Fourth Ventricle

Surgical exposure of intrinsic brainstem lesions through the floor of the 4th ventricle requires precise identification of facial nerve (CN VII) fibers to avoid damage. To assess the shape, size, and variability of the area where the facial nerve can be stimulated electrophysiologically on the surface of the rhomboid fossa. Over a period of 18 months, 20 patients were operated on for various brainstem and/or cerebellar lesions. Facial nerve fibers were stimulated to yield compound muscle action potentials (CMAP) in the target muscles. Using the sites of CMAP yield, a detailed functional map of the rhomboid fossa was constructed for each patient. Lesions resected included 14 gliomas, 5 cavernomas, and 1 epidermoid cyst. Of 40 response areas mapped, 19 reached the median sulcus. The distance from the obex to the caudal border of the response area ranged from 8 to 27 mm (median, 17 mm). The rostrocaudal length of the response area ranged from 2 to 15 mm (median, 5 mm). Facial nerve response areas showed large variability in size and position, even in patients with significant distance between the facial colliculus and underlying pathological lesion. Lesions located close to the facial colliculus markedly distorted the response area. This is the first documentation of variability in the CN VII response area in the rhomboid fossa. Knowledge of this remarkable variability may facilitate the assessment of safe entry zones to the brainstem and may contribute to improved outcome following neurosurgical interventions within this sensitive area of the brain.