Configuration-sensitive visual responses in the superior colliculus of the house mouse (Mus musculus domesticus)

In order to compare visual pattern discrimination by tectal neurons in distantly related vertebrate groups, collicular cells of mice were examined for their responses to each of three simple configurational stimuli commonly used in studies of amphibians. The stimuli consisted of a large square, a horizontal bar and a vertical bar moved at various velocities. Of the recorded units (n = 51), 30-50% significantly preferred the square to the other stimuli at medium (10 degrees/s) and high (67 degrees/s) velocities. Approximately 10% preferred the horizontal bar at these velocities. A significant discrimination between the horizontal and the vertical bar was found in 39% of the units at a velocity of 10 degrees/s, and in 61% at a velocity of 67 degrees/s. These response types are very similar to those found in amphibians; therefore, it is concluded that tectal configurational sensitivity may be a plesiomorphic tetrapod character resulting from basic properties of tectal neuronal circuitry.     

Quantitative analysis of nerve fibre densities in the cochlea of the house mouse (Mus musculus)

Transverse sections of the cochlear nerve, silver-stained surface preparations of the cochlea, and silver- and osmium-stained tangential sections of the cochlea of the house mouse were made to determine the number and density of nerve fibres entering the organ of Corti and their distribution to inner and outer hair cells along the cochlear spiral. A number of 12,578 ± 819 fibres was counted within the cochlear nerve, which is almost equal to the total number of 12,350 ± 810 fibres entering the organ of Corti. The 12,350 fibres divide into 9,780 (? 79%) fibres running to the inner hair cells, 703 (? 6%) basilar (afferent) fibres and 1,867 (? 15%) upper tunnel radial (efferent) fibres innervating the outer hair cells. About 93% of all afferent fibres are connected to the inner hair cells, and only 7% innervate outer hair cells. The density of fibres running to the inner hair cells varies considerably and has a significant (p < 0.01) absolute and relative maximum 3.7 mm and 2.9 mm from the apex respectively (total length: 6.84 mm) and decreases toward apex and base. The density of afferent fibres running to the outer hair cells shows a slow increase up to 2 mm from the apex, and remains on a constant low level (5.5 fibres per 40 μm) down to the base. The density of efferent fibres running to the outer hair cells increases linearly up to about 2 mm from the apex, remains rather constant (10 fibres per 40 μm) from 2 mm to 4 mm, and then decreases toward the base. Generally, the outer hair cells show a convergent innervation pattern, the inner hair cells a divergent one. The significance of the present measurements is discussed in relation to respective results from other mammals and in relation to auditory thresholds.     

Effects of external chemical environment on the developing olfactory bulbs of the mouse (Mus musculus)

Female mice were reared in observation incubators from day 1 of life for three weeks. During that time they were continuously exposed to the odors of either cyclooctanone, adult male mouse urine or distilled water. The growth rate was temporarily accelerated for the cyclooctanone-exposed mice. There was no difference in age at sexual maturation of the three groups. Olfactory preference, when adult, was not affected by early odor exposure, but sniffing behaviour was markedly increased in the urine-exposed mice as compared with the other two groups. The olfactory bulbs of the cyclooctanone-reared mice were larger than those of the other two groups. Mitral cells in the olfactory bulbs were examined histologically for abnormalities. All mice had some shrunken, darkly staining mitral cells, but the cyclooctanone-reared mice had twice as many as the other two groups, mainly in the dorsal half of the bulb. The urine-exposed mice also had more darkly staining cells than the control mice particularly in the dorsolateral region of the bulb, but also in the dorsomedial region.     

Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain

Defining how arginine vasopressin (AVP) acts centrally to regulate homeostasis and behavior is problematic, as AVP is made in multiple nuclei in the hypothalamus (i.e., paraventricular [PVN], supraoptic [SON], and suprachiasmatic [SCN]) and extended amygdala (i.e., bed nucleus of the stria terminalis [BNST] and medial amygdala [MeA]), and these groups of neurons have extensive projections throughout the brain. To understand the function of AVP, it is essential to know the site of origin of various projections. In mice, we used gonadectomy to eliminate gonadal steroid hormone–dependent expression of AVP in the BNST and MeA and electrolytic lesions to eliminate the SCN, effectively eliminating those AVP‐immunoreactive projections; we also quantified AVP‐immunoreactive fiber density in gonadectomized and sham‐operated male and female mice to examine sex differences in AVP innervation. Our results suggest that the BNST/MeA AVP system innervates regions containing major modulatory neurotransmitters (e.g., serotonin and dopamine) and thus may be involved in regulating behavioral state. Furthermore, this system may be biased toward the regulation of male behavior, given the numerous regions in which males have a denser AVP‐immunoreactive innervation than females. AVP from the SCN is found in regions important for the regulation of hormone output and behavior. Innervation from the PVN and SON is found in brain regions that likely work in concert with the well‐known peripheral AVP actions of controlling homeostasis and stress response; female‐biased sex differences in this system may be related to the heightened stress response observed in females. J. Comp. Neurol. 521:2321–2358, 2013. © 2012 Wiley Periodicals, Inc.     

Vasopressin receptors in the mouse (Mus musculus) brain: sex-related expression in the medial preoptic area and hypothalamus

We have investigated the distribution of vasopressin binding sites in the brain of male and female adult mice using a radio-iodinated ligand and film autoradiography. Vasopressin receptors were uncovered in various regions of the brain including the basal nucleus of Meynert, the substantia innominata, the hypothalamic paraventricular nucleus, the substantia nigra pars compacta and the hypoglossal nucleus. A sex-related difference in the expression of vasopressin receptors was seen in the medial preoptic area/anterior hypothalamus corresponding to the rat sexually dimorphic nucleus in the rat and in the hypothalamic mammillary nuclei. In both structures the autoradiographic labeling is more intense in females than in males. These observations confirm that vasopressin binding sites are present in the hypothalamic preoptic area of most species examined so far and that sex-related expression of neuropeptide receptors could trigger sex-related behavioral differences.     

The sharpening of frequency tuning curves requires patterned activity during development in the mouse, Mus musculus

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization of axo-axonic synapses in the piriform cortex of Mus musculus

Previous anatomical and physiological studies have established major glutamatergic and GABAergic neuronal subtypes within the piriform cortical circuits. However, quantitative information regarding axo-axonic inhibitory synapses mediated by chandelier cells across major cortical subdivisions of piriform cortex is lacking. Therefore, we examined the properties of these synapses across the entire piriform cortex. Our results show the following. 1) γ-Aminobutyric acid membrane transporter 1-positive varicosities, whose appearance resembles chandelier cartridges, are found around the initial segments of axons of glutamatergic cells across layers II and III. 2) Both the density of axo-axonic cartridges and the degree of γ-aminobutyric acid membrane transporter 1 innervation in each axo-axonic synapse are significantly higher in the piriform cortex than in the neocortex. 3) Glutamate decarboxylase 67, vesicular GABA transporter, and parvalbumin, but not calbindin, are colocalized with the presynaptic varicosities, whereas gephyrin, Na-K-2Cl cotransporter 1, and GABA(A) receptor α1 subunit, but not K-Cl cotransporter 2, are colocalized at the presumed postsynaptic sites. 4) The axo-axonic cartridges innervate the majority of excitatory neurons and are distributed more frequently in putative centrifugal cells and posterior piriform cortex. We further describe the morphology of chandelier cells by using parvalbumin-immunoreactivity and single-cell labeling. In summary, our results demonstrate that a small population of chandelier cells mediates abundant axo-axonic synapses across the entire piriform cortex. Because of the critical location of these inhibitory synapses in relation to action potential regulation, our results highlight a critical role of axo-axonic synapses in regulating information flow and olfactory-related oscillations within the piriform cortex in vivo.     

Novel males' capacity to disrupt early pregnancy in mice (Mus musculus) is attenuated via a chronic reduction of males' urinary 17beta-estradiol

Mature male mice of proven fertility were administered chronic oral doses of anastrozole, a potent aromatase inhibitor, and also given a low-phytoestrogen diet. Urine was taken non-invasively from such males and from untreated control males and assayed for 17beta-estradiol and testosterone via ELISA procedures. After 8 weeks of drug or vehicle administration, urinary 17beta-estradiol declined to significantly lower levels in anastrozole-treated males than in non-treated males, whereas testosterone levels were comparable in the two groups. Inseminated females were exposed to drug-treated, vehicle-treated, or no males during days 1-6 of gestation, around intrauterine implantation of fertilized ova. Females exposed to vehicle-treated males produced fewer litters than did those kept in isolation. Females exposed to anastrozole-treated males produced significantly more litters than did those exposed to vehicle-treated males. These data support the notion that male excretions of estrogens may in part mediate novel-male-induced pregnancy disruptions, although other influences of aromatization on behaviour and metabolism remain possibilities.     

The effects of age and sex on the detection of pure tones by adult CBA/CaJ mice (Mus musculus)

Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that the CBA/CaJ mouse strain is an appropriate model for the late-onset hearing loss found in humans. However, few studies have characterized hearing in these mice behaviorally using longitudinal methodologies. The goal of this research was to utilize a longitudinal design and operant conditioning procedures with positive reinforcement to construct audiograms and temporal integration functions in aging CBA/CaJ mice. In the first experiment, thresholds were collected for 8, 16, 24, 42, and 64 kHz pure tones in 30 male and 35 female CBA/CaJ mice. Similar to humans, mice had higher thresholds for high frequency tones than for low frequency pure tones across the lifespan. Female mice had better hearing acuity than males after 645 days of age. In the second experiment, temporal integration functions were constructed for 18 male and 18 female mice for 16 and 64 kHz tones varying in duration. Mice showed an increase in thresholds for tones shorter than 200 ms, reaching peak performance at shorter durations than other rodent species. Overall, CBA/CaJ mice experience ARHL for pure tones of different frequencies and durations, making them a good model for studies on hearing loss. These findings highlight the importance of using a wide range of stimuli and a longitudinal design when comparing presbycusis across different species.     

Evolutionary significance of delayed neurogenesis in the core versus shell auditory areas of Mus musculus

Early comparative embryogenesis can reflect the organization and evolutionary origins of brain areas. Neurogenesis in the auditory areas of sauropsids displays a clear core‐to‐shell distinction, but it remains unclear in mammals. To address this issue, [³H]‐thymidine was injected into pregnant mice on consecutive embryonic (E) days (E10–E19) to date neuronal birthdays. Immunohistochemistry for substance P, calbindin, and parvalbumin was conducted to distinguish the core and shell auditory regions. The results showed that: 1) cell generation began at E13 in the external or dorsal nucleus of the inferior colliculus (IC), but it did not start in the caudomedial portion of the central nucleus of IC, and significantly fewer cells were produced in the medial and rostromedial portions of the central nucleus of IC; 2) cells were generated at E11 in the dorsal and medial divisions of the medial geniculate complex (MGd and MGm, respectively), whereas cell generation was absent in the medial and rostromedial portions of the ventral medial geniculate complex (MGv), and fewer cells were produced in the caudomedial portion of MGv; 3) in the telencephalic auditory cortex, cells were produced at E11 or E12 in layer I and the subplate, which receive projections from the MGd and MGm. However, cell generation occurred at E13–E18 in layers II–VI, including the area receiving projections from the MGv. The core‐to‐shell distinction of neurogenesis is thus present in the mesencephalic to telencephalic auditory areas in the mouse. This distinction of neurogenesis is discussed from an evolutionary perspective. J. Comp. Neurol. 515:600–613, 2009. © 2009 Wiley‐Liss, Inc.     

Different regulation of adult hippocampal neurogenesis in Western house mice (Mus musculus domesticus) and C57BL/6 mice

Adult hippocampal neurogenesis (AHN) of laboratory rodents is enhanced by physical exercise in a running wheel. However, little is known about modulation of AHN in wild-living rodent species. The finding that AHN cannot be modulated by voluntary exercise in wild wood mice suggests that AHN may be regulated differently under natural conditions than in laboratory adapted animals. In order to minimize genetic influences, we aimed to investigate the genetically closest wild-living relatives of laboratory mice. Here, C57BL/6 mice and F1 offspring of wild house mice (Mus musculus domesticus) were tested in two different running paradigms: voluntary running and running-for-food - a condition in which mice had to run for their daily allowance of food. In house mice, we found a non-significant trend towards increased numbers of proliferating cells and doublecortin-positive immature neurons in both voluntary runners and runners-for-food. Voluntary running in C57BL/6 mice resulted in a 30% increase in cell proliferation and a pronounced 70% increase in doublecortin-positive cells. C57BL/6 runners-for-food ran as much as voluntary runners, but they showed no enhancement of cell proliferation, a small increase in the number of doublecortin-positive cells and more pyknotic cells compared to controls. Taken together, these findings suggest that motivational aspects of running are critical determinants of the increased cell proliferation in C57BL/6 mice. In contrast, running has smaller and context-independent effects in house mice. The findings imply a difference in the regulation of AHN in C57BL/6 mice and their wild-derived conspecifics.     

A set of 18 polymorphic microsatellite loci in the Algerian mouse,Mus spretus Lataste 1883 (Rodentia: Muridae)

A multiplex PCR assay was developed for the identification of polymorphic microsatellite loci (18) for the Algerian mouse, Mus spretus, using 454 GS-FLX Titanium pyrosequencing. The utility of these markers was evaluated in 184 individuals from for different Moroccan populations. Number of alleles per locus ranged from 10 to 39, with expected and observed heterozygosities ranging from 0.256 to 0.947 and from 0.259 to 0.926 respectively. None departures from Hardy–Weinberg equilibrium were observed at all loci. These markers will be valuable tools for population genetic studies in conservation management.     

Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic parameters that can be used for the prediction or diagnosis of DCI, or that inform on the pathogenesis of DCI and may serve as treatment targets. We included 24 studies that fulfilled predefined criteria and described 39 biomarkers. Only one study fulfilled predefined criteria for high quality. Since no parameter on admission was associated with DCI and in none of the included studies blood was drawn at the time of clinical deterioration, none of the studied parameters can presently be used for the prediction or diagnosis of DCI. Regarding the pathogenesis of DCI, it was shown that compared with patients without DCI those with DCI had higher levels of von Willebrand factor and platelet activating factor in plasma 5 to 9 days after aSAH, membrane tissue factor in cerebrospinal fluid 5 to 9 days after aSAH, and D-dimer in plasma 11 to 14 days after aSAH. Confirmation in high-quality studies is needed to investigate whether these parameters can serve as targets for new intervention studies.     

Quantitative analysis of neuronal response properties in primary and higher‐order auditory cortical fields of awake house mice (Mus musculus)

Because of its great genetic potential, the mouse (Mus musculus) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher‐order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III/IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher‐order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic‐tonic responses, tonic responses, and off‐responses), and degree of variation between the characteristic frequency (CF) and the best frequency (BF) (CF–BF relationship). Field similarities were noted as significant correlations between CFs and BFs, V‐shaped frequency tuning curves, similar minimum response thresholds and non‐monotonic rate‐level functions in approximately two‐thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior.     

The mouse light-dark paradigm: a review

1. The light/dark paradigm is based on the innate aversion of rodents to brightly illuminated areas and on the spontaneous exploratory behaviour of the animals, applying mild stressors i.e. novel environment and light. The test apparatus consists of a small dark secure compartment (one third) and a large illuminated aversive compartment (two thirds). 2. The test was developed with male mice. The strain, weight and age may be crucial factors. 3. The extent to which an anxiolytic compound can facilitate the exploratory activity depends on the baseline level in the control group. Differences between the type and severity of external stressors might account for variable results reported by different laboratories. 4. In conclusion, the black and white test may be useful to predict anxiolytic-like or anxiogenic-like activity in mice. Transitions have been reported to be an index of activity-exploration because of habituation over time and the time spent in each compartment to be a reflection of aversion. Classic anxiolytics (benzodiazepines) as well as the newer anxiolytic-like compounds (e.g. serotonergic drugs) can be detected using this paradigm. It has the advantages of being quick and easy to use, without requiring the prior training of animals.