Pain Perception Is Increased in Congenital but Not Late Onset Blindness

There is now ample evidence that blind individuals outperform sighted individuals in various tasks involving the non-visual senses. In line with these results, we recently showed that visual deprivation from birth leads to an increased sensitivity to pain. As many studies have shown that congenitally and late blind individuals show differences in their degree of compensatory plasticity, we here address the question whether late blind individuals also show hypersensitivity to nociceptive stimulation. We therefore compared pain thresholds and responses to supra-threshold nociceptive stimuli in congenitally blind, late blind and normally sighted volunteers. Participants also filled in questionnaires measuring attention and anxiety towards pain in everyday life. Results show that late blind participants have pain thresholds and ratings of supra-threshold heat nociceptive stimuli similar to the normally sighted, whereas congenitally blind participants are hypersensitive to nociceptive thermal stimuli. Furthermore, results of the pain questionnaires did not allow to discriminate late blind from normal sighted participants, whereas congenitally blind individuals had a different pattern of responses. Taken together, these results suggest that enhanced sensitivity to pain following visual deprivation is likely due to neuroplastic changes related to the early loss of vision.     

Olfactory Performance Is Predicted by Individual Sex-Atypicality,but Not Sexual Orientation

Many previous studies have reported robust sex differences in olfactory perception. However, both men and women can be expected to vary in the degree to which they exhibit olfactory performance considered typical of their own or the opposite sex. Sex-atypicality is often described in terms of childhood gender nonconformity, which, however, is not a perfect correlate of non-heterosexual orientation. Here we explored intrasexual variability in psychophysical olfactory performance in a sample of 156 individuals (83 non-heterosexual) and found the lowest odor identification scores in heterosexual men. However, when childhood gender nonconformity was entered in the model along with sexual orientation, better odor identification scores were exhibited by gender-nonconforming men, and greater olfactory sensitivity by gender-conforming women, irrespective of their sexual orientation. Thus, sex-atypicality, but not sexual orientation predicts olfactory performance, and we propose that this might not be limited to olfaction, but represent a more general phenomenon.     

Morphometric Changes of the Corpus Callosum in Congenital Blindness

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12% reduction in the splenium, and a 20% increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness.     

Photoreceptor Degeneration in Two Mouse Models for Congenital Stationary Night Blindness Type 2

Light-dependent conductance changes of voltage-gated Ca_v1.4 channels regulate neurotransmitter release at photoreceptor ribbon synapses. Mutations in the human CACNA1F gene encoding the α1F subunit of Ca_v1.4 channels cause an incomplete form of X-linked congenital stationary night blindness (CSNB2). Many CACNA1F mutations are loss-of-function mutations resulting in non-functional Ca_v1.4 channels, but some mutations alter the channels’ gating properties and, presumably, disturb Ca²⁺ influx at photoreceptor ribbon synapses. Notably, a CACNA1F mutation (I745T) was identified in a family with an uncommonly severe CSNB2-like phenotype, and, when expressed in a heterologous system, the mutation was shown to shift the voltage-dependence of channel activation, representing a gain-of-function. To gain insight into the pathomechanism that could explain the severity of this disorder, we generated a mouse model with the corresponding mutation in the murine Cacna1f gene (I756T) and compared it with a mouse model carrying a loss-of-function mutation (ΔEx14–17) in a longitudinal study up to eight months of age. In ΔEx14–17 mutants, the b-wave in the electroretinogram was absent, photoreceptor ribbon synapses were abnormal, and Ca²⁺ responses to depolarization of photoreceptor terminals were undetectable. In contrast, I756T mutants had a reduced scotopic b-wave, some intact rod ribbon synapses, and a strong, though abnormal, Ca²⁺ response to depolarization. Both mutants showed a progressive photoreceptor loss, but degeneration was more severe and significantly enhanced in the I756T mutants compared to the ΔEx14–17 mutants.     

Flavor Preference Learning Increases Olfactory and Gustatory Convergence onto Single Neurons in the Basolateral Amygdala but Not in the Insular Cortex in Rats

The basolateral amygdala (BLA) and the insular cortex (IC) represent two major areas for odor-taste associations, i.e. flavor integration. This learning may require the development of convergent odor and taste neuronal activation allowing the memory representation of such association. Yet identification of neurons that respond to such coincident input and the effect of flavor experience on odor-taste convergence remain unclear. In the present study we used the compartmental analysis of temporal activity using fluorescence in situ hybridization for Arc (catFISH) to visualize odor-taste convergence onto single neurons in the BLA and in the IC to assess the number of cells that were co-activated by both stimuli after odor-taste association. We used a sucrose conditioned odor preference as a flavor experience in rats, in which 9 odor-sucrose pairings induce a reliable odor-taste association. The results show that flavor experience induced a four-fold increase in the percentage of cells activated by both taste and odor stimulations in the BLA, but not in the IC. Because conditioned odor preference did not modify the number of cells responding selectively to one stimulus, this greater odor-taste convergence into individual BLA neurons suggests the recruitment of a neuronal population that can be activated by both odor and taste only after the association. We conclude that the development of convergent activation in amygdala neurons after odor-taste associative learning may provide a cellular basis of flavor memory.     

TRPM1 Is Mutated in Patients with Autosomal-Recessive Complete Congenital Stationary Night Blindness

Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in ∼60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.     

A Mutation in SLC24A1 Implicated in Autosomal-Recessive Congenital Stationary Night Blindness

Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder that can be associated with impaired night vision. The last decade has witnessed huge progress in ophthalmic genetics, including the identification of three genes implicated in the pathogenicity of autosomal-recessive CSNB. However, not all patients studied could be associated with mutations in these genes and thus other genes certainly underlie this disorder. Here, we report a large multigeneration family with five affected individuals manifesting symptoms of night blindness. A genome-wide scan localized the disease interval to chromosome 15q, and recombination events in affected individuals refined the critical interval to a 10.41 cM (6.53 Mb) region that harbors SLC24A1, a member of the solute carrier protein superfamily. Sequencing of all the coding exons identified a 2 bp deletion in exon 2: c.1613_1614del, which is predicted to result in a frame shift that leads to premature termination of SLC24A1 (p.F538CfsX23) and segregates with the disorder under an autosomal-recessive model. Expression analysis using mouse ocular tissues shows that Slc24a1 is expressed in the retina around postnatal day 7. In situ and immunohistological studies localized both SLC24A1 and Slc24a1 to the inner segment, outer and inner nuclear layers, and ganglion cells of the retina, respectively. Our data expand the genetic basis of CSNB and highlight the indispensible function of SLC24A1 in retinal function and/or maintenance in humans.     

Mutations in TRPM1 Are a Common Cause of Complete Congenital Stationary Night Blindness

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impaired night vision and variable decreased visual acuity. We report here that six out of eight female probands with autosomal-recessive complete CSNB (cCSNB) had mutations in TRPM1, a retinal transient receptor potential (TRP) cation channel gene. These data suggest that TRMP1 mutations are a major cause of autosomal-recessive CSNB in individuals of European ancestry. We localized TRPM1 in human retina to the ON bipolar cell dendrites in the outer plexifom layer. Our results suggest that in humans, TRPM1 is the channel gated by the mGluR6 (GRM6) signaling cascade, which results in the light-evoked response of ON bipolar cells. Finally, we showed that detailed electroretinography is an effective way to discriminate among patients with mutations in either TRPM1 or GRM6, another autosomal-recessive cCSNB disease gene. These results add to the growing importance of the diverse group of TRP channels in human disease and also provide new insights into retinal circuitry.     

Group Size Predicts Social but Not Nonsocial Cognition in Lemurs

The social intelligence hypothesis suggests that living in large social networks was the primary selective pressure for the evolution of complex cognition in primates. This hypothesis is supported by comparative studies demonstrating a positive relationship between social group size and relative brain size across primates. However, the relationship between brain size and cognition remains equivocal. Moreover, there have been no experimental studies directly testing the association between group size and cognition across primates. We tested the social intelligence hypothesis by comparing 6 primate species (total N = 96) characterized by different group sizes on two cognitive tasks. Here, we show that a species’ typical social group size predicts performance on cognitive measures of social cognition, but not a nonsocial measure of inhibitory control. We also show that a species’ mean brain size (in absolute or relative terms) does not predict performance on either task in these species. These data provide evidence for a relationship between group size and social cognition in primates, and reveal the potential for cognitive evolution without concomitant changes in brain size. Furthermore our results underscore the need for more empirical studies of animal cognition, which have the power to reveal species differences in cognition not detectable by proxy variables, such as brain size.     

Sleep Supports Memory of Odors in Adults but Not in Children

Sleep supports the consolidation of declarative memory in children and adults. However, it is unclear whether sleep improves odor memory in children as well as adults. Thirty healthy children (mean age of 10.6, ranging from 8–12 yrs.) and 30 healthy adults (mean age of 25.4, ranging from 20–30 yrs.) participated in an incidental odor recognition paradigm. While learning of 10 target odorants took place in the evening and retrieval (10 target and 10 distractor odorants) the next morning in the sleep groups (adults: n = 15, children: n = 15), the time schedule was vice versa in the wake groups (n = 15 each). During encoding, adults rated odors as being more familiar. After the retention interval, adult participants of the sleep group recognized odors better than adults in the wake group. While children in the wake group showed memory performance comparable to the adult wake group, the children sleep group performed worse than adult and children wake groups. Correlations between memory performance and familiarity ratings during encoding indicate that pre-experiences might be critical in determining whether sleep improves or worsens memory consolidation.     

Urinary but Not Brain Isatin Levels Are Reduced in Germ-Free Rats

Germ-free rats excreted considerably smaller amounts of the monoamine oxidase-inhibiting compound isatin than the substantially larger output by conventional animals of the same strain, although concentrations in brain and other tissues were similar in the two groups. Thus, isatin is likely to be elaborated both endogenously in rat tissues and "exogenously" by flora inhabiting the lumen of the alimentary tract.     

Nest, but Not Egg, Fidelity in a Territorial Salamander

Egg recognition and subsequent egg brooding are costly forms of parental investment in many species of vertebrates. Life history factors, such as coloniality or risk of brood parasitism, may constrain egg recognition in vertebrates. Female red-backed salamanders ( Plethodon cinereus ) from my study site are territorial and do not share nest sites with other females. They are terrestrial and neither they nor their eggs are likely to be displaced by environmental factors such as flooding. I experimentally tested, in the laboratory, the hypothesis that female red-backed salamanders can discriminate between their own eggs and the eggs of unfamiliar females. Each female was allowed to move about a test chamber containing two clutches of eggs, one clutch with which it was found in the forest and one that had been found with a distant female. Most females remained with one clutch of eggs, which they brooded during the entire observation period. However, they did not significantly prefer to brood their own eggs over the eggs of another female. In a corollary field experiment, I tested whether brooding females that were displaced 1 m from their nest sites would return to their territories and commence brooding behaviour within 3 d. All 10 displaced females returned to their own nest within this time period and were found brooding their eggs. Because female red-backed salamanders at my study site do not tend to share nest sites with other females and because their eggs remain in stationary nests, selection may not have favoured egg recognition. However, the results suggest that female salamanders indirectly recognize their own eggs by actively recognizing their territorial nest sites.     

Nitric Oxide-Mediated Erectile Effects of Galantide but Not Galanin in Vivo

The purpose of this study was to investigate the in vivo effects of intracavernosal injections of galanin and galantide (a specific galanin receptor antagonist) on penile erection in the anesthetized cat. Erectile responses to galanin and galantide were compared with responses to a standard triple drug combination [1.65 mg papaverine, 25 μg phentolamine, and 0.5 μg prostaglandin E₁ (PGE₁)]. Intracavernosal injections of galanin (3–100 nmol) and galantide (0.1–3 nmol) induced penile erection in a dose-dependent manner. In terms of relative potency, galantide was approximately 100-fold more potent than galanin at increasing cavernosal pressure. The maximal increases in intracavernosal pressure in response to galanin and galantide were 83 and 95%, respectively, of the control triple drug combination. The total durations of erectile response caused by these peptides were significantly shorter (P < 0.05) than those by the triple drug combination. The nitric oxide synthase inhibitor L-NAME (20 mg) significantly decreased the erectile response in the cat to galantide but not to galanin, while the K⁺_ATP channel antagonist U-37883A (3 mg) had no effect on the erectile response to galanin nor galantide. The results of the present study demonstrate that galantide, a putative antagonist for the galanin receptor, has more potent agonist activity than galanin in increasing intracavernosal pressure in the cat. Moreover, these data suggest that galantide, but not galanin, causes penile erection by an NO/cGMP-dependent mechanism. This is the first study to demonstrate that galanin may play a role in the physiology of penile erection.     

The Amusic Brain: Lost in Music,but Not in Space

Congenital amusia is a neurogenetic disorder of music processing that is currently ascribed to a deficit in pitch processing. A recent study challenges this view and claims the disorder might arise as a consequence of a general spatial-processing deficit. Here, we assessed spatial processing abilities in two independent samples of individuals with congenital amusia by using line bisection tasks (Experiment 1) and a mental rotation task (Experiment 2). Both amusics and controls showed the classical spatial effects on bisection performance and on mental rotation performance, and amusics and controls did not differ from each other. These results indicate that the neurocognitive impairment of congenital amusia does not affect the processing of space.     

DNA Barcoding Works in Practice but Not in (Neutral) Theory

Background

DNA barcode differences within animal species are usually much less than differences among species, making it generally straightforward to match unknowns to a reference library. Here we aim to better understand the evolutionary mechanisms underlying this usual “barcode gap” pattern. We employ avian barcode libraries to test a central prediction of neutral theory, namely, intraspecific variation equals 2 Nµ, where N is population size and µ is mutations per site per generation. Birds are uniquely suited for this task: they have the best-known species limits, are well represented in barcode libraries, and, most critically, are the only large group with documented census population sizes. In addition, we ask if mitochondrial molecular clock measurements conform to neutral theory prediction of clock rate equals µ.

Results

Intraspecific COI barcode variation was uniformly low regardless of census population size (n = 142 species in 15 families). Apparent outliers reflected lumping of reproductively isolated populations or hybrid lineages. Re-analysis of a published survey of cytochrome b variation in diverse birds (n = 93 species in 39 families) further confirmed uniformly low intraspecific variation. Hybridization/gene flow among species/populations was the main limitation to DNA barcode identification.

Conclusions/Significance

To our knowledge, this is the first large study of animal mitochondrial diversity using actual census population sizes and the first to test outliers for population structure. Our finding of universally low intraspecific variation contradicts a central prediction of neutral theory and is not readily accounted for by commonly proposed ad hoc modifications. We argue that the weight of evidence–low intraspecific variation and the molecular clock–indicates neutral evolution plays a minor role in mitochondrial sequence evolution. As an alternate paradigm consistent with empirical data, we propose extreme purifying selection, including at synonymous sites, limits variation within species and continuous adaptive selection drives the molecular clock.     

Superior performance of African runners in warm humid but not in cool environmental conditions.

The purpose of this study was to examine the running performances and associated thermoregulatory responses of African and Caucasian runners in cool and warm conditions. On two separate occasions, 12 (n = 6 African, n = 6 Caucasian) well-trained men ran on a motorized treadmill at 70% of peak treadmill running velocity for 30 min followed by an 8-km self-paced performance run (PR) in cool (15 degrees C) or warm (35 degrees C) humid (60% relative humidity) conditions. Time to complete the PR in the cool condition was not different between groups ( approximately 27 min) but was significantly longer in warm conditions for Caucasian (33.0 +/- 1.6 min) vs. African (29.7 +/- 2.3 min, P < 0.01) runners. Rectal temperatures were not different between groups but were higher during warm compared with cool conditions. During the 8-km PR, sweat rates for Africans (25.3 +/- 2.3 ml/min) were lower compared with Caucasians (32.2 +/- 4.1 ml/min; P < 0.01). Relative rates of heat production were less for Africans than Caucasians in the heat. The finding that African runners ran faster only in the heat despite similar thermoregulatory responses as Caucasian runners suggests that the larger Caucasians reduce their running speed to ensure an optimal rate of heat storage without developing dangerous hyperthermia. According to this model, the superior running performance in the heat of these African runners can be partly attributed to their smaller size and hence their capacity to run faster in the heat while storing heat at the same rate as heavier Caucasian runners.