Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2

Neurogenèse dans le cerveau adulte. Conséquences fonctionnelles

Dans le cerveau adulte des Mammifères, des neuroblastes sont produits en permanence dans la zone subgranulaire de l’hippocampe et la zone subventriculaire (ZSV) du cerveau antérieur. Dans cette revue, nous décrivons le rôle déterminant d’un certain nombre de facteurs physiologiques et environnementaux dans la régulation de la neurogenèse hippocampique. Les neuroblastes issus de la SVZ migrent en direction du bulbe olfactif à l’intérieur duquel ils se différencient en interneurones. Les données présentées ont pour objectif de préciser les processus de production, de survie et les conséquences fonctionnelles de ces neurones nouvellement générés. Nous montrons qu’un environnement olfactif enrichi augmente dans le bulbe olfactif adulte la densité des neurones nouvellement générés. Ces effets ne sont pas la conséquence d’une augmentation du taux de prolifération des neuroblastes mais d’une augmentation de la probabilité de survie des nouveaux interneurones. Parallèlement, ces conditions d’élevage sont à l’origine de plus grandes facultés de mémoire olfactive des animaux. Ainsi la régulation par l’activité bulbaire d’un remplacement constitutif permanent des interneurones semble jouer un rôle majeur dans les processus de mémoire olfactive

Alcohol-induced Osteonecrosis - dose and duration effects.

International audienc

Short-term survival of newborn neurons in the adult olfactory bulb after exposure to a complex odor environment.

International audienceIn the olfactory bulb of adult mice, new neurons are continually integrated into existing neuronal networks. Previous studies have demonstrated that exposure to a complex odor environment increases the incorporation of newborn bulbar neurons without modifying the proliferation rate. Whether this incorporation is transient or leads to the long-lasting presence of new neurons has not yet been answered. Because a transient increase of new neurons impacts olfactory information processing differently than a long-lasting increase, we conducted experiments to investigate the time course of survival and cell death of newly generated bulbar neurons following exposure to an enriched olfactory environment. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were counted at several survival time points thereafter. Interestingly, whereas the number of surviving BrdU-labeled cells was elevated at the time when animals were withdrawn from their enriched housing, this number returned to control level 1 month later. Similarly, when olfactory memory was investigated, we found that the improvement of short-term memory, induced by enriched odor exposure, lasted less than 1 month. These findings indicate not only that the recruitment of newborn neurons closely followed the degree of environment complexity, but also that olfactory memory is tightly associated with the level of ongoing neurogenesis in the adult olfactory bulb

HVC interneurons are not renewed in adult male zebra finches.

Adult neurogenesis is a widespread phenomenon in many species, from invertebrates to humans. In songbirds, the telencephalic region, high vocal center (HVC), continuously integrates new neurons in adulthood. This nucleus consists of a heterogenous population of inhibitory interneurons (HVC(IN)) and two populations of projection neurons that send axons towards either the robust nucleus of the arcopallium (HVC(RA)) or the striatal nucleus area X (HVC(X)). New HVC neurons were initially inferred to be interneurons, because they lacked retrograde labelling from the HVC's targets. Later studies using different tracers demonstrated that HVC(RA) are replaced but HVC(X) are not. Whether interneurons are also renewed became an open question. As the HVC's neuronal populations display different physiological properties and functions, we asked whether adult HVC indeed recruits two neuronal populations or whether only the HVC(RA) undergo renewal in adult male zebra finches. We show that one month after being born in the lateral ventricle, 42% of the newborn HVC neurons were retrogradely labelled by tracer injections into the RA. However, the remaining 58% were not immunoreactive for the neurotransmitter GABA, nor for the calcium-binding proteins, parvalbumin (PA), calbindin (CB) and calretinin (CR) that characterize different classes of HVC(IN). We further established that simultaneous application of parvalbumin, calbindin and calretinin antibodies to HVC revealed approximately the same fraction of HVC neurons, i.e. 10%, as could be detected by GABA immunoreactivity. This implies that the sum of HVC(IN) expressing the different calcium-binding proteins constitute all inhibitory HVC(IN). Together these results strongly suggest that only HVC(RA) are recruited into the adult HVC

Cerebellar Contribution to Spatial Navigation: New Insights into Potential Mechanisms

SIXTH INTERNATIONAL SYMPOSIUM OF SRC, Rome, ITALY, JUL 03-04, 2014International audienceThe contribution of the cerebellum to the non-motor aspects of spatial navigation is now established, but the mechanisms of its participation remain unclear. The L7-PKCI mouse model, in which inhibited PKC activity suppresses parallel fiber-Purkinje cell long-term depression (LTD), provides the opportunity to study their spatial abilities in the absence of any motor impairment. L7-PKCI mice are deficient in the spatial but not the cued version of the watermaze task. Their performances are preserved when alleys guide their trajectories in the starmaze task, suggesting that cerebellar PKC-dependent mechanisms are required for the production of an optimal trajectory toward a goal. Furthermore, electrophysiological recordings in freely moving L7-PKCI mice revealed that their hippocampal place cell properties are affected when they have to rely on self motion information: in the absence of external information as well as in a conflicting situation between self-motion and external information. This suggests that the cerebellum is involved in the processing of self-motion information and is required for the construction of the spatial representation in the hippocampus

Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory

In the mammalian forebrain, most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles, including a discrete area of the subventricular zone (SVZ). In this region, neurogenesis continues into adulthood. Most of the cells generated in the SVZ are neuronal precursors with progeny that migrate rostrally along a pathway known as the rostral migratory stream before they reach the main olfactory bulb (MOB) where they differentiate into local interneurons. The olfactory system thus provides an attractive model to investigate neuronal production and survival, processes involving interplay between genetic and epigenetic influences. The present study was conducted to investigate whether exposure to an odorenriched environment affects neurogenesis and learning in adult mice. Animals housed in either a standard or an odorenriched environment for 40 d were injected intraperitoneall

Cerebellum Shapes Hippocampal Spatial Code

International audienceno abstrac