Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

An Immunocompetent Mongolian Gerbil Model for Hepatitis E Virus Genotype 1 Infection.

BACKGROUND & AIMS: Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection. METHODS: Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated. RESULTS: We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model. CONCLUSIONS: HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV.

Clinical Pathogenesis, Molecular Mechanisms of Gastric Cancer Development.

The human pathogen Helicobacter pylori is the strongest known risk factor for gastric disease and cancer, and gastric cancer remains a leading cause of cancer-related death across the globe. Carcinogenic mechanisms associated with H. pylori are multifactorial and are driven by bacterial virulence constituents, host immune responses, environmental factors such as iron and salt, and the microbiota. Infection with strains that harbor the cytotoxin-associated genes (cag) pathogenicity island, which encodes a type IV secretion system (T4SS) confer increased risk for developing more severe gastric diseases. Other important H. pylori virulence factors that augment disease progression include vacuolating cytotoxin A (VacA), specifically type s1m1 vacA alleles, serine protease HtrA, and the outer-membrane adhesins HopQ, BabA, SabA and OipA. Additional risk factors for gastric cancer include dietary factors such as diets that are high in salt or low in iron, H. pylori-induced perturbations of the gastric microbiome, host genetic polymorphisms, and infection with Epstein-Barr virus. This chapter discusses in detail host factors and how H. pylori virulence factors augment the risk of developing gastric cancer in human patients as well as how the Mongolian gerbil model has been used to define mechanisms of H. pylori-induced inflammation and cancer.

CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus.

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.

Differential susceptibility of Onchocerca ochengi adult male worms to flubendazole in gerbils and hamsters.

Onchocerciasis is a devastating skin and eye disease that afflicts about 21 million people, most of whom live in sub-Saharan Africa. Its control with the microfilaricidal drug ivermectin is limited, thus necessitating the development of preclinical animal models to aid in the discovery of a macrofilaricide. Previously, we found that Onchocerca ochengi (the closest relative of the human O. volvulus) worm masses survive better in hamsters than in gerbils. The aim of this study was to compare the survival of O. ochengi adult male worms and their susceptibility to flubendazole (FBZ, a macrofilaricide) in gerbils and hamsters. The animals were intraperitoneally implanted with O. ochengi male worms, treated with FBZ, and sacrificed 35 days post-implantation. Unlike gerbils which had some worms moving freely in the peritoneum and some in newly formed nodules (neo-nodules), all the worms in the hamsters were found in neo-nodules. FBZ significantly decreased worm burden, motility, and viability in gerbils whereas it had no significant effect in hamsters. These results highlight a major difference in how O. ochengi adult male worms are sustained and affected by FBZ in gerbils compared to hamsters. Understanding the difference between these two models is important in the development of effective macrofilaricides for onchocerciasis.

Cochlear Ribbon Synapses in Aged Gerbils.

In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell's modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.

Selective Interruption of Auditory Interhemispheric Cross Talk Impairs Discrimination Learning of Frequency-Modulated Tone Direction But Not Gap Detection and Discrimination.

Functional hemispheric lateralization is a basic principle of brain organization. In the auditory domain, the right auditory cortex (AC) determines the pitch direction of continuous auditory stimuli whereas the left AC discriminates gaps in these stimuli. The involved functional interactions between the two sides, mediated by commissural connections, are poorly understood. Here, we selectively disrupted the interhemispheric cross talk from the left to the right primary AC and vice versa using chromophore-targeted laser-induced apoptosis of the respective projection neurons, which make up 6-17% of all AC neurons in Layers III, V, and VI. Following photolysis, male gerbils were trained in a first experimental set to discriminate between rising and falling frequency-modulated (FM) tone sweeps. The acquisition of the task was significantly delayed in lesioned animals of either lesion direction. However, the final discrimination performance and hit rate was lowest for animals with left-side lesioned commissural neurons, demonstrating that also information from the left AC is relevant for FM direction learning. Photolysis after successful learning did not affect the retrieval of the learned task, indicating that the disruption during learning was not because of a general functional impairment. In a second experimental set, the gerbil's ability to detect and discriminate small silent gaps of varying length within FM sweeps was tested. This ability was also preserved after interhemispheric disruption. Taken together, interhemispheric communication between the left and right AC is important for the acquisition of FM tone direction learning but not for its retrieval and for gap detection and gap duration discrimination.SIGNIFICANCE STATEMENT Hemispheric lateralization of neuronal functions such as speech and music processing in humans are common throughout the brain; however, the involved interhemispheric interactions are ill-defined. Here, we show that the selective photolytic disruption of auditory cortical commissural connections in rodents impairs the acquisition but not retrieval of a frequency-modulated tone direction discrimination task. The final discrimination performance and hit rate was lowest for animals with lesioned left-to-right-side projections; thus, although right auditory cortex is dominant, left auditory cortex is also relevant for learning this task. The detection and discrimination of small gaps within the tone sweeps remain intact, suggesting a pathway for the processing of these temporal structures, which could be independent from the lesioned interhemispheric cross talk.

Cochlear aging disrupts the correlation between spontaneous rate- and sound-level coding in auditory nerve fibers.

The spiking activity of auditory nerve fibers (ANFs) transmits information about the acoustic environment from the cochlea to the central auditory system. Increasing age leads to degeneration of cochlear tissues, including the sensory hair cells and stria vascularis. Here, we aim to identify the functional effects of such age-related cochlear pathologies of ANFs. Rate-level functions (RLFs) were recorded from single-unit ANFs of young adult (n = 52, 3-12 months) and quiet-aged (n = 24, >36 months) Mongolian gerbils of either sex. RLFs were used to determine sensitivity and spontaneous rates (SRs) and were classified into flat-saturating, sloping-saturating, and straight categories, as previously established. A physiologically based cochlear model, adapted for the gerbil, was used to simulate the effects of cochlear degeneration on ANF physiology. In ANFs tuned to low frequencies (<3.5 kHz), SR was lower in those of aged gerbils, while an age-related loss of low-SR fibers was evident in ANFs tuned to high frequencies. These changes in SR distribution did not affect the typical SR versus sensitivity correlation. The distribution of RLF types among low-SR fibers, however, shifted toward that of high-SR fibers, specifically showing more fast-saturating and fewer sloping-saturating RLFs. A modeled striatal degeneration, which affects the combined inner hair cell and synaptic output, reduced SR but left RLF type unchanged. An additional reduced basilar membrane gain, which decreased sensitivity, explained the changed RLF types. Overall, the data indicated age-related changes in the characteristics of single ANFs that blurred the established relationships between SR and RLF types.NEW & NOTEWORTHY Auditory nerve fibers, which connect the cochlea to the central auditory system, change their encoding of sound level in aged gerbils. In addition to a general shift to higher levels, indicative of decreased sensitivity, level coding was also differentially affected in fibers with low- and high-spontaneous rates. Loss of low-spontaneous rate fibers, combined with a general decrease of spontaneous rate, further blurs the categorization of auditory nerve fiber types in the aged gerbil.

The effects of 20-hydroxyecdysone on nuclear shape, heterochromatin quantity and gray-level co-occurrence matrix texture analysis of adrenal zona fasciculata cells in an obese gerbil (Gerbillus tarabuli) model for metabolic syndrome: a correlational study.

The aim of this study was to reveal the effects of obesity and phytotherapy with 20-hydroxyecdysone (20E) on the nuclei of adrenal zona fasciculata (ZF) in the gerbil Gerbillus tarabuli by analyzing nuclear shape and gray-level co-occurrence matrix (GLCM) texture characteristics and by quantifying heterochromatin. Twelve gerbils were divided into three groups: control (C), HC and HC-20E (animals receiving a high-calorie-diet without or with a supplement of 20E, respectively). The adrenals were removed and fixed for histological and statistical analysis. Principal component analysis showed a positive correlation of area, perimeter and textural correlation in C. Nevertheless, a negative correlation was recorded for contrast and entropy. The obesity caused a disorder in nuclear texture; negative correlation was noted with heterochromatin fraction, which may be related to increased ZF activity. However, administration of 20E seems to improve the nuclear state by preserving circularity, uniformity and homogeneity of nuclei as well as the proportion of heterochromatin, which could be a sign of a downregulation of cell activity.Our results suggest that new techniques of image processing could contribute to the understanding of nuclear changes associated with obesity and its possible therapy in this gerbil model for metabolic syndrome.

The effects of sodium sulfite on Helicobacter pylori by establishing a hypoxic environment.

Helicobacter pylori (H. pylori) is an obligate microaerobion and does not survive in low oxygen. Sodium sulfite (SS) reacts and consume oxygen in solutions. The present study aimed to investigate the effects of SS on H. pylori. The effects of SS on oxygen concentrations in solutions and on H. pylori in vivo and in vitro were examined, and the mechanisms involved were explored. The results showed that SS decreased the oxygen concentration in water and artificial gastric juice. In Columbia blood agar and special peptone broth, SS concentration-dependently inhibited the proliferation of H. pylori ATCC43504 and Sydney strain-1 in Columbia blood agar or special peptone broth, and dose-dependently decreased the number of H. pylori in Mongolian gerbils and Kunming mouse infection models. The H. pylori was relapsed in 2 weeks withdrawal and the recurrence in the SS group was lower than that in the positive triple drug group. These effects were superior to positive triple drugs. After SS treatments, the cell membrane and cytoplasm structure of H. pylori were disrupted. SS-induced oxygen-free environment initially blocked aerobic respiration, triggered oxidative stress, disturbed energy production. In conclusion, SS consumes oxygen and creates an oxygen-free environment in which H. pylori does not survive. The present study provides a new strategy and perspective for the clinical treatment of H. pylori infectious disease.

Survival of worm masses of Onchocerca ochengi in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model.

Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been hindered by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. ochengi female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using "proof-of-concept" studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or collagenase-liberated O. ochengi worm masses, and necropsied at various time points to test for survival. Recovered worm masses were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation of 15 worm masses, a median of 7.00 (4.00-10.00) was recovered from hamsters, and 2.50 (2.00-4.00) from gerbils. Worm masses recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with collagenase-liberated worm masses. FBZ had no significant effect on the number of worm masses recovered, but enhanced embryo degradation in gerbils and reduced worm mass viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. ochengi. The hamsters appeared to maintain the worms longer, compared to gerbils.

Pharmacologic treatments in preclinical tinnitus models with special focus on Ginkgo biloba leaf extract EGb 761®.

Tinnitus is defined as the perception of sound in the absence of external acoustic stimuli. Frequent comorbidities or associated factors are depression, anxiety, concentration problems, insomnia, resignation, helplessness, headache, bruxism, or social isolation, just to name a few. Although many therapeutic approaches have already been tested with varying success, there still is no cure available for tinnitus. The search for an effective treatment has been hampered by the fact that the mechanisms of tinnitus development are still not fully understood, although several models are available and discussed in this review. Our review will give a brief overview about preclinical models, presenting the heterogeneity of tinnitus sub-types depending on the different inner ear and brain structures involved in tinnitus etiology and pathogenesis. Based on these models we introduce the different target structures and transmitter systems implicated in tinnitus development and provide an extensive overview on preclinical drug-based therapeutic approaches that have been explored in various animal models. As the special extract from Ginkgo biloba leaves EGb 761® has been the most widely tested drug in both non-clinical tinnitus models as well as in clinical trials, a special focus will be given to EGb 761®. The efficacy of terpene lactones, flavone glycosides and proanthocyanidines with their distinct contribution to the overall efficacy profile of the multi-constituent drug EGb 761® will be discussed.

Female Prostate Development: Morphological Analysis of the Budding Dynamic.

The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20-E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.

Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration.

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Anterior segment dysmorphogenesis of the eye and glaucoma in MG-W gerbils.

Unilaterally swollen eyes were histopathologically characterized in four MG-W gerbils. The primary lesions resided in the anterior segment of the eye where neural crest cells play a critical role in embryonic development. They included indistinct filtration angle, unformed canal of Schlemm, hypoplastic iris, and ciliary body. The findings noted in the retina, optic nerve, optic tract, and lateral geniculate nucleus were consistent with the lesions induced following the persistent elevation of intraocular pressure as a result of insufficient drainage of aqueous humor. Thus, the present cases observed in the eyes of MG-W gerbils exemplified the anterior segment dysmorphogenesis associated with inadequate neural crest migration or differentiation, leading to subsequent glaucoma.

Release from informational masking by auditory stream segregation: perception and its neural correlate.

In the analysis of acoustic scenes, we easily miss sounds or are insensitive to sound features that are salient if presented in isolation. This insensitivity that is not due to interference in the inner ear is termed informational masking (IM). So far, the cellular mechanisms underlying IM remained elusive. Here, we apply a sequential IM paradigm to humans and gerbils using a sound level increment detection task determining the sensitivity to target tones in a background of standard (same frequency) and distracting tones (varying in level and frequency). The amount of IM that was indicated by the level increment thresholds depended on the frequency separation between the distracting and the standard and target tones. In humans and gerbils, we observed similar perceptual thresholds. A release from IM of more than 20 dB was observed in both species if the distracting tones were well segregated in frequency from the other tones. Neuronal rate responses elicited by similar sequences in gerbil inferior colliculus and auditory cortex were recorded. At both levels of the auditory pathway, the neuronal thresholds obtained with a signal-detection-theoretic approach deducing the sensitivity from the analysis of the neurons' receiver operating characteristics matched the psychophysical thresholds revealing that IM already emerges at midbrain level. By applying objective response measures in physiology and psychophysics, we demonstrated that the population of neurons has a sufficient sensitivity for explaining the perceptual level increment thresholds indicating IM. There was a good correspondence between the neuronal and perceptual release from IM being related to auditory stream segregation.

Evidence for the origin of the binaural interaction component of the auditory brainstem response.

The binaural interaction component (BIC) represents the mismatch between auditory brainstem responses (ABR) obtained with binaural stimulation and the sum of ABRs obtained with monaural left and right stimulation. It is generally assumed that the BIC reflects binaural integration. Its potential use as a diagnostic tool, however, is hampered by the lack of direct evidence about its origin. While an origin at the initial site of binaural integration seems likely, there is no general agreement on the contribution of the two primary candidate nuclei, the lateral and medial superior olives (LSO and MSO, respectively). Here, we recorded local field potentials (LFP) and responses of units in the LSO and MSO of Mongolian gerbils (Meriones unguiculatus), presenting clicks with an interaural time or level difference (ITD and ILD, respectively), while simultaneously recording ABR. We determined the BIC from the ABR and, importantly, from LFP and responses of units in the LSO and MSO. If stimulus-induced changes in the ABR-derived BIC have their source in the LSO and/or MSO, we expect coherent changes in the unit-derived and the ABR-derived BIC. We find that BIC obtained from LSO units exhibits the same ITD and ILD dependence as the ABR-derived BIC. Neither BIC obtained from MSO units nor LFP-derived BIC recorded in either LSO or MSO did. The data thus strongly suggest that it is the activity of LSO units in the gerbil that is decisive for the generation of the ABR-derived BIC, determining its properties.

Dopaminergic neuromodulation of high gamma stimulus phase-locking in gerbil primary auditory cortex mediated by D1/D5-receptors.

Cortical release of the neurotransmitter dopamine has been implied in adapting cortical processing with respect to various functions including coding of stimulus salience, expectancy, error prediction, behavioral relevance and learning. Dopamine agonists have been shown to modulate recurrent cortico-thalamic feedback, and should therefore also affect synchronization and amplitude of thalamo-cortical oscillations. In this study, we have used multitaper spectral and time-frequency analysis of stimulus-evoked and spontaneous current source density patterns in primary auditory cortex of Mongolian gerbils to characterize dopaminergic neuromodulation of the oscillatory structure of current sources and sinks. We systemically applied D1/D5-receptor agonist SKF-38393 followed by competitive D1/D5-receptor antagonist SCH-23390. Our results reveal an increase in stimulus phase-locking in the high gamma-band (88-97 Hz) by SKF-38393, specifically in layers III/IV at the best frequency, which occurred at 20 ms after tone onset, and was reversed by SCH-23390. However, changes in induced oscillatory power after SKF-38393 treatment occurred stimulus-independently in the background activity in different layers than phase-locking effects and were not reversed by SCH-23390. These effects might either reflect longer-lasting changes in neural background noise, non-specific changes due to ketamine anesthesia, or an interaction of both. Without concomitant stimulus-induced power increase, increased stimulus phase-locking in layers III/IV indicates enhanced phase-resetting of neural oscillations by the stimulus after D1/D5-receptor activation. The frequency characteristics, together with the demonstrated stimulus specificity and layer specificity, suggest that changes in phase-resetting originate from dopaminergic neuromodulation of thalamo-cortical interactions. Enhanced phase-resetting might be a key step in the recruitment of cortical activity modes interpreting sensory input.

Testosterone dependent territorial aggression is modulated by cohabitation with a female in male Mongolian gerbils (Meriones unguiculatus).

Most mammal studies on the neuroendocrine mechanisms of territorial aggression have demonstrated that testosterone (T) is required for the display of territorial aggression. However, the relationship between T and aggression is more complex and may be modulated by social factor. The aim of this study was to determine the role of T in territorial aggression in the Mongolian gerbil (Meriones unguiculatus), and the effect of social factors on the modulation of this behavior. The relationship between T and territorial aggression was analyzed using castration and T replacement in two social contexts: male-male and male-female cohabitation. Plasma T concentrations in males of all groups were quantified by radioimmunoassay (RIA). T concentrations were compared using two-way ANOVA. Only sham-castrated and castrated males with T replacement in male-female cohabitation showed aggression, whereas castrated gerbils in the same condition were not aggressive. This indicates that T is the hormone that maintains territorial aggression, but mating is a modulator stimulus. The modulator effect of mating in territorial aggression was associated with an increase in T, but it seems that other mechanisms are involved in the regulation of this behavior, since castrated males with T replacement in the male-male cohabitation did not exhibit aggression, although they had T concentrations as high as these males that received the same treatment, but that cohabited with a female. These results suggest that T is involved in the mechanisms that regulate territorial aggression in the male Mongolian gerbil, and that the cohabitation with a female modulates this behavior.

Postnatal exposure to finasteride causes different effects on the prostate of male and female gerbils.

The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α-reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 µg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three-dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.