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Fernando Nottebohm

Publications and source records attributed to Fernando Nottebohm.

18 recordsLinked to original sources
PubMed2006

High levels of new neuron addition persist when the sensitive period for song learning is experimentally prolonged.

Socially reared zebra finch males imitate a song they hear during posthatching days 30-65; during this time, many new neurons are added to the high vocal center (HVC), a forebrain nucleus necessary for the production of learned song. New neuron addition drops sharply after day 65, and no new songs are imitated. In contrast, male zebra finches reared in isolation from other males have more variable songs at day 65 and thereafter can still imitate new sounds (Eales, 1985). We show that, in isolate birds, a greater number of new neurons continues to be added to HVC during the next 85 d, and this number correlates with syllable variability. We suggest that new neuron addition and turnover facilitate song change and that this effect lingers when an expected learning event is delayed.

Animals↗
PubMed2006

Expression profiling of intermingled long-range projection neurons harvested by laser capture microdissection.

Gene expression data are most useful if they can be associated with specific cell types. This is particularly so in an organ such as the brain, where many different cell types lie in close proximity to each other. We used zebra finches (Taeniopygia guttata), fluorescent tracers and laser capture microdissection (LCM) to collect projection neurons and their RNAs from two interspersed populations from the same animal. RNA amplified from each cell class was reverse transcribed, fluorescently labeled, and hybridized to cDNA microarrays of genes expressed in the zebra finch brain. We applied strict fold-expression criteria, supplemented by statistical analysis, to single out genes that showed the most extreme and consistent differential expression between the two cell classes. Confirmation of the true expression pattern of these genes was made by in situ hybridization and Taqman quantitative PCR (qPCR). High quality RNA was obtained, too, from backfilled neurons birth-dated with bromodeoxyuridine (BrdU). We also quantified changes in the levels of three genes after singing behavior using qPCR. Thus, we have brought together a combination of techniques allowing for the molecular profiling of intermingled populations of projection neurons of known connectivity, age and experience, which should constitute a powerful tool for CNS research.

Animals↗
PubMed2005

Social and spatial changes induce multiple survival regimes for new neurons in two regions of the adult brain: An anatomical representation of time?

Male zebra finches reared in family groups were housed initially in small indoors cages with three other companions. At 4-5 months of age these birds were treated with [(3)H]-thymidine and then placed in large outdoors aviaries by themselves or with other zebra finches. Counts of new neurons were made 40, 60 and 150 days after the change in housing. Recruitment of new neurons in nidopallium caudale (NC) was higher than in the hippocampal complex (HC); but in both brain regions it was higher in communally housed birds than in birds housed singly, suggesting that the complexity of the social setting affects new neuron survival. In addition, the new neurons lived longer in rostral NC than in its caudal counterpart, and neuronal turnover was faster and more significant in NC than in HC. Albeit indirect, this may be the first suggestion that different parts of the brain upgrade memories at different time intervals, yielding an anatomical representation of time.

Analysis of Variance↗
PubMed2005

Variable rate of singing and variable song duration are associated with high immediate early gene expression in two anterior forebrain song nuclei.

The duration of songs and the intervals between these songs are more variable when wild, adult, free-ranging chipping sparrows sing at dawn than when they sing during the day. The more variable delivery is used to interact with males, and the stereotyped delivery is used to attract females. In captive birds, however, the variability observed at dawn persists during the day. We quantified the expression of an immediate early gene, ZENK, in wild and captive birds and found that the level of song-associated ZENK expression in two song nuclei, Area X and lMAN, was positively related to variability in song duration and intersong interval and could be dissociated from the social context in which the song occurred. Thus, a combination of field and laboratory approaches helped us identify nuclei, context, and behavioral features associated with a change in gene expression thought to be a marker of behavioral variability.

Analysis of Variance↗
PubMed2005

Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels.

Might there be systematic differences in gene expression between neurons that undergo spontaneous replacement in the adult brain and those that do not? We first explored this possibility in the high vocal center (HVC) of male zebra finches by using a combination of neuronal tracers, laser capture microdissection, and RNA profiling. HVC has two kinds of projection neurons, one of which continues to be produced and replaced in adulthood. HVC neurons of the replaceable kind showed a consistent and robust underexpression of the deubiquitination gene ubiquitin carboxyl-terminal hydrolase (UCHL1) that is involved with protein degradation. Singing behavior, known to increase the survival of adult-born HVC neurons in birds, significantly up-regulated the levels of UCHL1 in the replaceable neurons but not in their equally active nonreplaceable counterparts. We then looked in the mouse brain and found relatively low UCHL1 expression in granule neurons of the hippocampus and olfactory bulb, two well characterized types of replaceable neurons in mammals. UCHL1 dysfunction has been associated with neurodegeneration in Parkinson's, Alzheimer's, and Huntington's disease patients. In all these instances, reduced UCHL1 function may jeopardize the survival of CNS neurons.

Animals↗
PubMed2005

Freedom and rules: the acquisition and reprogramming of a bird's learned song.

Canary song is hierarchically structured: Short stereotyped syllables are repeated to form phrases, which in turn are arranged to form songs. This structure occurs even in the songs of young isolates, which suggests that innate rules govern canary song development. However, juveniles that had never heard normal song imitated abnormal synthetic songs with great accuracy, even when the tutor songs lacked phrasing. As the birds matured, imitated songs were reprogrammed to form typical canary phrasing. Thus, imitation and innate song constraints are separate processes that can be segregated in time: freedom in youth, rules in adulthood.

Aging↗
PubMed2004

Juvenile zebra finches can use multiple strategies to learn the same song.

Does the ontogeny of vocal imitation follow a set program that, given a target sound, unfolds in a predictable manner, or is it more like problem solving, with many possible solutions? We report that juvenile male zebra finches, Taeniopygia guttata, can master their imitation of the same song in various ways; these developmental trajectories are sensitive to the social setting in which the bird grows up. A variety of vocal developmental trajectories have also been described in infants. Are these many ways to learn unique to the vocal domain or a hallmark of advanced brain function?

Animal Communication↗
PubMed2004

Timing of brain-derived neurotrophic factor exposure affects life expectancy of new neurons.

The high vocal center (HVC) of adult male canaries, Serinus canaria, is necessary for the production of learned song. New neurons are added to HVC every day, where they replace older neurons that have died, but the length of their survival depends on the time of year when they are born. A great number of HVC neurons born in the fall, when adult canaries learn a new song, are still present 8 mo later, when this song is used during the breeding season. By contrast, most of the neurons born in HVC in the spring, when little song learning takes place, disappear much sooner. Here we show that infusion of brain-derived neurotrophic factor into HVC during days 14-20 after new HVC neurons are born in the spring confers on them a life expectancy comparable to that of fall-born neurons; this extension on life is not seen when infusion occurs 10 days earlier or later. We suggest that there is, in the adult HVC, a subset of neurons whose life expectancy is determined by brain-derived neurotrophic factor during a sensitive period soon after these neurons reach destination and start forming connections.

Animals↗
PubMed2004

A conversation with Fernando Nottebohm, PhD. Interviewed by Michael Eisenstein.

During the last 30 years, a number of revolutionary discoveries in the field of neuroscience have come from what was, at first, an unexpected direction: songbird research. Investigations into seasonal and sex-specific differences in birdsong development have led to important revelations about the impact of sex hormones on brain development and the hormonally controlled plasticity of brain structure, as well as the particularly surprising discovery that neurogenesis continues to occur in the adult brain (see Harding, p. 28). The work of Fernando Nottebohm is widely recognized as having played a key role in bringing these findings to light and thus forcing a general re-examination of established principles of neuroscience. Fernando Nottebohm is Dorothea L. Leonhardt Distinguished Professor at The Rockefeller University, and Director of The Rockefeller Field Research Center for Ethology and Ecology, a 1,200-acre facility located in Millbrook, NY, that provides researchers the opportunity to study behavior and brain function under natural conditions. Nottebohm's pioneering work on the neural control of birdsong has led to major discoveries with large impacts in the fields of animal behavior and neuroscience, and has made him one of the founders of neuroethology, the study of how the nervous system controls animal behavior. Nottebohm is a Member of the National Academy of Sciences, USA, and a Fellow of the American Association for the Advancement of Science and of the American Academy of Arts and Sciences. We had a chance to sit down with him to discuss his distinguished career working with laboratory birds.

Animals↗
PubMed2004

The road we travelled: discovery, choreography, and significance of brain replaceable neurons.

Neurons are constantly added to the telencephalon of songbirds. In the high vocal center (HVC), where this has been studied, new neurons replace older ones that died. Peaks in replacement are seasonal and affect some neuronal classes but not others. Peaks in replacement coincide with peaks in information acquisition. The new neurons are produced by division of cells in the wall of the lateral ventricle. Where studied closely, the neuronal stem cells proved to be radial glia. Life expectancy of the new neurons ranges from weeks to months. New neuron survival is regulated by vacancies, hormones, and activity. The immediate agent of new neuron survival is, in some cases, brain-derived neurotrophic factor (BDNF). The effect of BDNF is maximal 14-20 days after the cells are born, when they are establishing their connections. These observations are now being extended to other vertebrates and may apply, to varying degrees, to all of them. The function of neuronal replacement in healthy adult brain remains unclear. If synaptic number and efficacy sufficed as mechanisms for long-term memory storage and could be adjusted again and again to incorporate new memories, then neuronal replacement would seem unnecessary. Since it occurs, it seems reasonable to suppose that replacement serves to maintain learning potential in a way that could not be done just by synaptic change. Long-term memories may be encoded by long-term changes in gene expression akin to a last step in cell differentiation. If so, neuronal replacement may be the adult brain's way of striking a balance between limited memory space and the need to acquire new memories. The testing of this hypothesis remains in the future. This chapter tells how neuronal replacement was discovered in the adult songbird brain.

Animals↗
PubMed2004

Age and experience affect the recruitment of new neurons to the song system of zebra finches during the sensitive period for song learning: ditto for vocal learning in humans?

Vocal learning in songbirds and humans is a complex learned skill with sensory, motor, and social aspects. It culminates in the imitation of sounds produced by other, usually older individuals. Song learning and language learning may differ in their cognitive content, but both require coordination of auditory feedback and fine motor control, which may be supported by similar brain structures. Vocal learning in birds as in humans requires the use of forebrain networks; in songbirds these networks are thought to be related, in part, to the frontal association cortex-basal ganglia loops that mature in humans at adolescence.

Aging↗
PubMed2003

Vocal learning in birds and humans.

Vocal learning is the modification of vocal output by reference to auditory information. It allows for the imitation and improvisation of sounds that otherwise would not occur. The emergence of this skill may have been a primary step in the evolution of human language, but vocal learning is not unique to humans. It also occurs in songbirds, where its biology can be studied with greater ease. What follows is a review of some of the salient anatomical, developmental, and behavioral features of vocal learning, alongside parallels and differences between vocal learning in songbirds and humans.

Age Factors↗
PubMed2002

Gonads and singing play separate, additive roles in new neuron recruitment in adult canary brain.

New neurons are constantly added to the high vocal center (HVC) of adult male canaries, Serinus canaria. Singing and testosterone (T) are known to promote this addition, but it is not known whether either variable can act on its own and what is their effect when acting together. We studied this question by castrating adult male canaries in late summer and quantifying their song in early fall. Intact birds served as controls. A 5 d systemic treatment of two daily injections of the cell birth marker 3H-thymidine started 10 d after surgery. Twenty days after the first 3H-thymidine injection and for a period of 1 month, we quantified the singing of all birds, which were then killed. Amount of singing, syllable diversity, and song stability were similar in intacts and castrates. When castrates and intacts that sang comparable amounts were compared, the number of 3H-labeled HVC neurons was 2.6 times higher in intacts than in castrates. In castrates with plasma T levels that were undetectable, the mean amount of singing was positively related to the number of new neurons. We suggest that singing and gonadal factors promote, separately, the recruitment of new neurons and that when they exert this effect together they do so in an additive manner.

Animals↗
PubMed2002

Experience affects recruitment of new neurons but not adult neuron number.

It is not known whether the addition of new neurons to the high vocal center (HVC) of juvenile zebra finches permits vocal learning or is the consequence of it. To tease apart these two, we performed surgery on 26-d-old juveniles. The operations were removal of both cochleae and unilateral or bilateral denervation of the syrinx. Ability to imitate a tutor song was little affected by unilateral syringeal denervation but was severely hindered by bilateral denervation or deafening. Recruitment of new HVC neurons was studied by injecting BrdU, a cell birth marker, on post-hatching days 61-65 and killing the animals 30 d later. Deafening or bilateral denervation did not alter the number of BrdU-labeled neurons in HVC, but unilateral denervation nearly doubled this number in the intact side. This doubling was transient, was blocked by deafening, and was not seen in birds that received BrdU injections earlier or later in vocal ontogeny. The adult number of HVC neurons was not affected by any of our surgical procedures. Apparently experience does not affect the total number of neurons in adult HVC, but some kinds of experience can, during narrowly defined times, influence the recruitment of new HVC neurons.

Animals↗
PubMed2002

Neuronal replacement in adult brain.

The discovery of spontaneous neuronal replacement in the adult vertebrate brain has changed the way in which we think about the biology of memory. This is because neuronal replacement is likely to have an impact on what a brain remembers and what it learns. Neuronal replacement has also changed the way in which we go about exploring new strategies for brain repair. Our new outlook on both these matters is all the more remarkable because of the pervasiveness of the earlier dogma, which for warm-blooded vertebrates relegated neurogenesis to embryonic development and, for a few neuronal classes, early postnatal life. The discovery of constant neuronal replacement in the adult brain was remarkable, too, in that it was not required by what we thought to be the logic of nervous system function. Moreover, no previous facts prepared us for it. Much of the modern theory of learning embraced the view of modifiable synapses as the key players in learning and as the repositories of memory. But if this were so, what would be the point of neuronal replacement in healthy brain tissue? In what follows, I will briefly review the work of Joseph Altman, because he was the first one to challenge the notion that new neurons were not produced in adulthood. I will then review what we know about neuronal replacement in the song system of birds, which my laboratory has studied for many years. In closing, I will offer a general theory of long-term memory that, if true, might explain why adult nervous systems constantly replace some of their neurons.

Aging↗