Maternal care, including by non-biological parents, is important for offspring survival1–8. Oxytocin1,2,9–15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress15. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.
Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD). To assess the consequences of mutant protein when huntingtin is limiting, we have studied three lines of compound heterozygous mice in which both copies of the HD gene homolog (Hdh) were altered, resulting in greatly reduced levels of huntingtin with a normal human polyglutamine length (Q20) and/or an expanded disease-associated segment (Q111): Hdh(neoQ20)/Hdh(neoQ20), Hdh(neoQ20)/Hdh(null) and Hdh(neoQ20)/Hdh(neoQ111). All surviving mice in each of the three lines were small from birth, and had variable movement abnormalities. Magnetic resonance micro-imaging and histological evaluation showed enlarged ventricles in approximately 50% of the Hdh(neoQ20)/Hdh(neoQ111) and Hdh(neoQ20)/Hdh(null) mice, revealing a developmental defect that does not worsen with age. Only Hdh(neoQ20)/Hdh(neoQ111) mice exhibited a rapidly progressive movement disorder that, in the absence of striatal pathology, begins with hind-limb clasping during tail suspension and tail stiffness during walking by 3-4 months of age, and then progresses to paralysis of the limbs and tail, hypokinesis and premature death, usually by 12 months of age. Thus, dramatically reduced huntingtin levels fail to support normal development in mice, resulting in reduced body size, movement abnormalities and a variable increase in ventricle volume. On this sensitized background, mutant huntingtin causes a rapid neurological disease, distinct from the HD-pathogenic process. These results raise the possibility that therapeutic elimination of huntingtin in HD patients could lead to unintended neurological, as well as developmental side-effects.
Maternal care is profoundly important for mammalian survival, and maternal behaviors can also be expressed by non-biological parents after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone released in the brain by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with in vivo recordings from virgin PVN cells, including from identified oxytocin neurons. Mothers engaged virgins in maternal care by ensuring that virgins were in the nest, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup distress calls. Thus rodent maternal behavior can be learned by social transmission, and our results describe a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin. One Sentence Summary:Mother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.Main Text: Social interactions, such as pair bond formation and child rearing, are fundamental aspects of animal and human behavior (1-4). Parental care is especially important in mammals, and new parents must rapidly and reliably express a number of behaviors required for survival of offspring. Some parental behavior is therefore believed to be at least in part innate and hard-wired, or gated by neurochemical changes after mating. However, maternal behavior can also be acquired from experience. In humans and other primates, individuals other than the biological parents can learn to successfully care for children after instruction or observation of experienced caretakers and infants (1-8). It is unclear how expression of such alloparenting behaviors in rodents or other species can also be learned from experience, and if so, what mechanisms of neuromodulation and plasticity underlie learning of maternal behaviors.One of the most important molecular modulators of neural circuit function for social interactions and maternal physiology is the evolutionarily-ancient peptide hormone oxytocin (1,2, 9,10). In mammals, oxytocin is released from the hypothalamus and is critical for childbirth and lactation (10,11). Oxytocin also acts in the brain where it is believed to increase the salience of social information, enhancing pair bonding and maternal behavior (1,9,(12)(13)(14)(15), and enabling onset of alloparenting in mice. Specifically, pup-naïve virgin female mice initially ignore neonates and cues related to infant need, e.g., ultrasonic distress calls emitted by pups isolated from the nest (15). However, after several days of co-housing with experienced mothers ('dams') and litters, most virgin females become mate...
Cochlear implants are neuroprosthetic devices that can provide hearing to deaf patients1. Despite signi cant bene ts offered by cochlear implants, there are highly variable outcomes in how quickly hearing is restored and perceptual accuracy after months or years of use2,3. Cochlear implant use is believed to require neuroplasticity within the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to outcome variability4-7. Despite extensive studies on how cochlear implants activate the auditory system4,8-12, our understanding of cochlear implant-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator norepinephrine from the brainstem locus coeruleus. Here we examined behavioral responses and neural activity in locus coeruleus and auditory cortex of deafened rats tted with multi-channel cochlear implants. Animals were trained on a reward-based auditory task, with considerable individual differences of learning rates and maximum performance. Photometry from locus coeruleus predicted when implanted subjects would begin responding to sounds and longer-term perceptual accuracy, which were augmented by optogenetic locus coeruleus stimulation. Auditory cortical responses to cochlear implant stimulation re ected behavioral performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically-relevant target for optimizing neuroprosthetic device use. Main TextCochlear implants are major biomedical devices, and an exemplary success story of the application of foundational neuroscience research and use of brain-machine interface neuroprosthetics to treat a widespread neurological condition: hearing loss 1-5 . However, the auditory bene ts provided by a cochlear implant are not instantaneous, in contrast to the ampli cation of acoustic input provided by commercial hearing aids. Some patients acquire a degree of speech comprehension with the cochlear implant a few hours after activation, but many patients unfortunately require months or even years post-implantation to achieve optimum levels of speech perception 2,3 . There are many open questions about the behavioral characteristics of this adaptation process in human listeners and the underlying neurophysiological changes 13,14 . Measuring how cochlear implants activate the central auditory system or other brain areas is technically complicated due to signi cant limitations with imaging in patients with implanted metallic medical devices 15 . Historically there have also been considerable challenges with experimental animal models of cochlear implant use, especially with the aims of monitoring and manipulating neural activity in implanted freely-behaving subjects. Here we addressed these issues by utilizing our recently-developed system for studying behaviorally-and physiologically-validated cochlear implant use in rats 16 , and examined neuromodulation and plasti...
Labeled protein-based scaffolds have become a popular biomaterial for tissue-engineered implants. Labeling of protein biomaterials, including with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging...
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