RESUMEN
Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome's potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects alpha-diversity of the offspring stomach and fecal microbiomes. We provide evidence from beta-diversity analyses that paternal diet and maternal behavior induced community-wide shifts to the adult offspring gut microbiome. Additionally, we show that paternal HFD significantly altered the adult offspring Firmicutes to Bacteroidetes ratio, an indicator of obesogenic potential in the gut microbiome. Additional machine-learning analyses indicated that microbial species driving these differences converged on Bifidobacterium pseudolongum. These results suggest that differences in early-life care induced by paternal diet and maternal care significantly influence the microbiota composition of offspring through the microbiota-gut-brain axis, having implications for adult stress reactivity.
Asunto(s)
Microbioma Gastrointestinal , Animales , Dieta Alta en Grasa/efectos adversos , Padre , Heces/microbiología , Femenino , Humanos , Masculino , ARN Ribosómico 16S/genética , RatasRESUMEN
Interneurons are critical for information processing in the cortex. In vitro optogenetic studies in mouse primary visual cortex (V1) have sketched the connectivity of a local neural circuit comprising excitatory pyramidal neurons and distinct interneuron subtypes that express parvalbumin (Pvalb+), somatostatin (SOM+), or vasoactive intestinal peptide (VIP+). However, in vivo studies focusing on V1 orientation tuning have ascribed discrepant computational roles to specific interneuron subtypes. Here, we sought to clarify the differences between interneuron subtypes by examining the effects of optogenetic activation of Pvalb+, SOM+, or VIP+ interneurons on contrast tuning of V1 neurons while also accounting for cortical depth and photostimulation intensity. We found that illumination of the cortical surface produced a similar spectrum of saturating additive photostimulation effects in all 3 interneuron subtypes, which varied with cortical depth rather than light intensity in Pvalb+ and SOM+ cells. Pyramidal cell modulation was well explained by a conductance-based model that incorporated these interneuron photostimulation effects.
Asunto(s)
Interneuronas , Optogenética , Animales , Interneuronas/fisiología , Ratones , Neuronas , Parvalbúminas , Péptido Intestinal Vasoactivo/genética , Percepción Visual/fisiologíaRESUMEN
The mouse primary visual cortex (V1) has become an important brain area for exploring how neural circuits process information. Optogenetic tools have helped to outline the connectivity of a local V1 circuit comprising excitatory pyramidal neurons and several genetically-defined inhibitory interneuron subtypes that express parvalbumin, somatostatin, or vasoactive intestinal peptide. Optogenetic modulation of individual interneuron subtypes can alter the visual responsiveness of pyramidal neurons with distinct forms of inhibition and disinhibition. However, different interneuron subtypes have potentially opposing actions, and the potency of their effects relative to each other remains unclear. Therefore, in this study we simultaneously optogenetically activated all interneuron subtypes during visual processing to explore whether any single inhibitory effect would predominate. This aggregate interneuron activation consistently inhibited pyramidal neurons in a divisive manner, which was essentially identical to the pattern of inhibition produced by activating parvalbumin-expressing interneurons alone.
Asunto(s)
Interneuronas/fisiología , Inhibición Neural/fisiología , Corteza Visual/fisiología , Percepción Visual/fisiología , Animales , Ratones , Ratones Transgénicos , Optogenética , Células Piramidales/fisiologíaRESUMEN
Paternal preconception risk factors (e.g. stress, diet, drug use) correlate with metabolic dysfunction in offspring, which is often comorbid with depressive and anxiety-like phenotypes. Detection of these risk factors or deleterious phenotypes informs a female about prevailing ecological demands, in addition to potential adverse environment-induced phenotypes that may be disseminated to her offspring. We examined whether a F0 male rat's prior exposure to an obesogenic high-fat diet (HFD) influences a female's attraction towards a male, subsequent mother-infant interactions and the development of defensive (emotional) responses in the F1 offspring. Females displayed less interest in the HFD exposed F0 males relative to control diet-exposed F0 males. Dams that reared F1 offspring in larger, semi-naturalistic housing provided more licking and grooming and active arched-back-nursing behavior. However, some of these effects interacted with paternal experience. F0 HFD and maternal rearing environment revealed sex-dependent, between group differences in F1 offspring wean weight, juvenile social interactions and anxiety-like behavior in adolescence. Our results show for the first time in mammals that male exposure to HFD may contribute to stable behavioral variation among females in courtship, maternal care, even when the females are not directly exposed to a HFD, and anxiety-like behavior in F1 offspring. Furthermore, when offspring were exposed to a predatory threat, hypothalamic Crf gene regulation was influenced by early housing. These results, together with our previous findings, suggest that paternal experience and maternal rearing conditions can influence maternal behavior and development of defensive responses of offspring.
Asunto(s)
Matrimonio/psicología , Conducta Materna/psicología , Herencia Paterna/fisiología , Animales , Ansiedad/fisiopatología , Conducta Animal/fisiología , Dieta Alta en Grasa/efectos adversos , Dieta Alta en Grasa/psicología , Padre , Femenino , Masculino , Conducta Materna/fisiología , Relaciones Madre-Hijo , Madres , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Ratas Long-EvansRESUMEN
Visual impairments and retinal abnormalities occur in patients with Alzheimer's disease (AD) and in mouse models of AD. It is important to know the visual ability of mouse models of AD to ensure that age-related cognitive deficits are not confounded by visual impairments. Using OptoMotry, the spatial frequency thresholds of male and female 3xTg-AD mice did not differ from their B6129SF2 wildtype controls between 1-18 months of age, but females had higher spatial frequency thresholds than males. However, the differences were quite small, and the visual ability of all mice was comparable to that of C57BL/6 mice.
Asunto(s)
Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Proteínas tau/metabolismo , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Caracteres Sexuales , Visión Ocular , Proteínas tau/genéticaRESUMEN
Information processing in the visual system is shaped by recent stimulus history, such that prolonged viewing of an adapting stimulus can alter the perception of subsequently presented test stimuli. In the tilt-after-effect, the perceived orientation of a grating is often repelled away from the orientation of a previously viewed adapting grating. A possible neural correlate for the tilt-after-effect has been described in cat and macaque primary visual cortex (V1), where adaptation produces repulsive shifts in the orientation tuning curves of V1 neurons. We investigated adaptation to stimulus orientation in mouse V1 to determine whether known species differences in orientation processing, notably V1 functional architecture and proportion of tightly tuned cells, are important for these repulsive shifts. Unlike the consistent repulsion reported in other species, we found that repulsion was only about twice as common as attraction in our mouse data. Furthermore, adapted responses were attenuated across all orientations. A simple model that captured key physiological findings reported in cats and mice indicated that the greater proportion of broadly tuned neurons in mice may explain the observed species differences in adaptation.
Asunto(s)
Adaptación Fisiológica/fisiología , Orientación Espacial/fisiología , Corteza Visual/fisiología , Percepción Visual/fisiología , Potenciales de Acción/fisiología , Animales , Masculino , Ratones Endogámicos C57BL , Neuronas/fisiología , Estimulación Luminosa/métodosRESUMEN
Visual adaptation illusions indicate that our perception is influenced not only by the current stimulus but also by what we have seen in the recent past. Adaptation to stimulus contrast (the relative luminance created by edges or contours in a scene) induces the perception of the stimulus fading away and increases the contrast detection threshold in psychophysical tests [1, 2]. Neural correlates of contrast adaptation have been described throughout the visual system including the retina [3], dorsal lateral geniculate nucleus (dLGN) [4, 5], primary visual cortex (V1) [6], and parietal cortex [7]. The apparent ubiquity of adaptation at all stages raises the question of how this process cascades across brain regions [8]. Focusing on V1, adaptation could be inherited from pre-cortical stages, arise from synaptic depression at the thalamo-cortical synapse [9], or develop locally, but what is the weighting of these contributions? Because contrast adaptation in mouse V1 is similar to classical animal models [10, 11], we took advantage of the optogenetic tools available in mice to disentangle the processes contributing to adaptation in V1. We disrupted cortical adaptation by optogenetically silencing V1 and found that adaptation measured in V1 now resembled that observed in dLGN. Thus, the majority of adaptation seen in V1 neurons arises through local activity-dependent processes, with smaller contributions from dLGN inheritance and synaptic depression at the thalamo-cortical synapse. Furthermore, modeling indicates that divisive scaling of the weakly adapted dLGN input can predict some of the emerging features of V1 adaptation.
Asunto(s)
Neuronas GABAérgicas/fisiología , Corteza Visual/fisiología , Adaptación Fisiológica , Animales , Femenino , Interneuronas/fisiología , Masculino , Ratones , Ratones TransgénicosRESUMEN
Prolonged viewing of high contrast gratings alters perceived stimulus contrast, and produces characteristic changes in the contrast response functions of neurons in the primary visual cortex (V1). This is referred to as contrast adaptation. Although contrast adaptation has been well-studied, its underlying neural mechanisms are not well-understood. Therefore, we investigated contrast adaptation in mouse V1 with the goal of establishing a quantitative description of this phenomenon in a genetically manipulable animal model. One interesting aspect of contrast adaptation that has been observed both perceptually and in single unit studies is its specificity for the spatial and temporal characteristics of the stimulus. Therefore, in the present work we determined if the magnitude of contrast adaptation in mouse V1 neurons was dependent on the spatial frequency and temporal frequency of the adapting grating. We used protocols that were readily comparable with previous studies in cats and primates, and also a novel contrast ramp stimulus that characterized the spatial and temporal specificity of contrast adaptation simultaneously. Similar to previous work in higher mammals, we found that contrast adaptation was strongest when the spatial frequency and temporal frequency of the adapting grating matched the test stimulus. This suggests similar mechanisms underlying contrast adaptation across animal models and indicates that the rapidly advancing genetic tools available in mice could be used to provide insights into this phenomenon.