Biomedical subjects

S W Bottjer

Publications and source records attributed to S W Bottjer.

At least 37 records · Page 2Linked to original sources

PubMed1993

Testosterone-induced changes in adult canary brain are reversible.

Brain nuclei that control song are larger in male canaries, which sing, than in females, which sing rarely or not at all. Treatment of adult female canaries with testosterone (T) induces song production and causes song-control nuclei to grow, approaching the volumes observed in males. For example, the higher vocal center (HVC) of adult females approximately doubles in size by 1 month following the onset of T treatment. Male HVC projects to a second telencephalic nucleus, RA (the robust nucleus of the archistriatum), which projects in turn to the vocal motor neurons. Whether HVC makes a similar connection in female canaries is not known, although HVC and RA are not functionally connected in female zebra finches, a species in which testosterone does not induce neural or behavioral changes in the adult song system. This experiment investigated whether HVC makes an efferent projection to RA in normal adult female canaries, or if T is necessary to induce the growth of this connection. In addition, we examined whether T-induced changes in adult female canary brain are reversible. Adult female canaries received systemic T implants that were removed after 4 weeks; these birds were killed 4 weeks after T removal (Testosterone-Removal, T-R). Separate groups of control birds received either (a) T implants for 4 weeks which were not removed (Testosterone-Control, T-C) or (b) empty implants (Untreated-Control, O-C). Crystals of the fluorescent tracer DiI were placed in the song-control nucleus HVC in order to anterogradely label both efferent targets of HVC, RA and Area X. Projections from HVC to RA and Area X were present in all treatment groups including untreated controls, and did not appear to differ either qualitatively or quantitatively. Thus, formation of efferent connections from HVC may be prerequisite to hormone-induced expression of song behavior in adult songbirds. The volumes of RA and Area X were measured using the distribution of anterograde label as well as their appearance in Nissl-stained tissue. RA was larger in T-treated control birds than in untreated controls. Experimental birds in which T was given and then removed (T-R) had RA volumes closer in size to untreated controls (O-C). Because the volume of RA in T-treated controls (T-C) was larger than that of birds that did not receive T (O-C), we conclude that the volume of RA increased in both T-C and T-R birds but regressed upon removal of T in T-R birds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Neurogenesis in adult canary telencephalon is independent of gonadal hormone levels.

Neurons generated in adulthood are found throughout the canary telencephalon. We are interested in the factors that control the rate of proliferation of stem cells that give rise to these new neurons. The rate of incorporation of newly generated neurons into vocal-control regions varies seasonally. This difference could reflect a higher rate of neurogenesis, a lower rate of cell death, or an altered migration. We examined the incidence of thymidine-labeled cells in the telencephalic ventricular zone of adult canaries as a function of variations in gonadal hormone levels. Adult female canaries maintained on a short-day photoperiod were anesthetized and gonadectomized. Four separate groups of birds received systemic exposure to either testosterone, estradiol, a combination of an anti-androgen and an inhibitor of estrogen synthesis, or nothing. All birds were also implanted with an osmotic minipump that released 3H-thymidine for 3 d and were killed 4 or 7 d following the onset of treatment. Analysis of autoradiograms revealed no differences between groups in the incidence of labeling within the ventricular zone either at the level of the anterior commissure or directly adjacent to the vocal-control nucleus HVC (higher vocal center). These results suggest that sex steroids do not regulate the rate of cell division in the ventricular zone. Seasonal differences in the incorporation of labeled cells into HVC may therefore be due to regulation of neurogenesis by photoperiodic factors other than gonadal steroids or to some other cellular mechanism, such as differential migration or survival of neurons.

Animals↗

PubMed1993

Induced cell death in a thalamic nucleus during a restricted period of zebra finch vocal development.

A discrete network of forebrain nuclei underlies vocal learning and production in male zebra finches. Three nuclei within this network form a neural pathway that is particularly important for vocal learning in juveniles: area X of the avian striatum projects to the medial dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of any of these nuclei in juvenile birds disrupt normal vocal development, whereas the same lesions in adult birds have no effect on already-learned song. Because numerous studies have shown that neuronal survival in the developing nervous system depends on access to efferent targets, we have investigated the possibility that the survival of DLM neurons is similarly regulated over the course of vocal learning. Thus, the efferent target of DLM (IMAN) was lesioned electrolytically in male birds at various stages of vocal development (20, 40, 60 d of age and adult) and birds were killed either 2, 4, or 6 d postlesion. Electrolytic lesions of IMAN removed the single identified efferent target of DLM projection neurons and axotomized the terminal arborizations of these neurons. Although DLM does not normally lose neurons during vocal development, IMAN lesions in 20-d-old birds yielded numerous pyknotic cells throughout DLM by 4 d postlesion and a two-thirds reduction in DLM neuron density by 6 d postlesion. In contrast, IMAN lesions in adult birds had little or no effect on neuronal survival in DLM. Analysis of 40-d-old birds revealed significant but less substantial cell loss than in 20-d-old birds, whereas 60-d-old birds were not different from adults. The age-related decline in the vulnerability of DLM cells to IMAN lesion-induced death suggests that factors that regulate DLM neuron survival may also be involved in the acquisition of learned vocal behavior in songbirds.

Aging↗

PubMed1992

Growth and regression of thalamic efferents in the song-control system of male zebra finches.

A serial forebrain pathway in the songbird brain plays a critical role in vocal learning; Area X of the parolfactory lobe (X) projects to the medial portion of the dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of this pathway in juvenile birds disrupt vocal development, whereas identical lesions in adult birds do not influence the production of already learned song. During the course of vocal learning, IMAN undergoes a phase of massive neuronal loss, whereas the neuronal population of X more than doubles. In the present study, the development of neuron number in DLM was analyzed and found not to change during the course of vocal learning. Anterograde DiI labeling of DLM efferent fibers was then used to analyze the morphological development of this projection in relation to both the loss of neurons from lMAN and the loss of the ability of X-DLM-lMAN lesions to influence vocal production. We found that DLM axons arrive within lMAN by 15 days of age, prior to both the loss of neurons from lMAN and the onset of vocal production. The volume of anterograde DiI label over lMAN did not change between 15 and 20 days of age, but this volume more than doubled between 20 and 35 days of age. During this phase of exuberant growth, anterograde label matched the dorsal border of lMAN but extended beyond all other borders of lMAN into a surrounding "shell" of parvicellular neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1992

Castration and antisteroid treatment impair vocal learning in male zebra finches.

Both song behavior and its neural substrate are hormone sensitive: castrated adult male zebra finches need replacement of gonadal steroids in order to restore normal levels of song production, and sex steroids are necessary to establish male-typical neural song-control circuits during early development. This pattern of results suggests that hormones may be required for normal development of learned song behavior, but evidence that steroids are necessary for normal neural and behavioral development during song learning has been lacking. We addressed this question by attempting to eliminate the effects of gonadal steroids in juvenile male zebra finches between the time of initial song production and adulthood. Males were castrated at 20 days of age and received systemic implants of either an antiandrogen (flutamide), an antiestrogen (tamoxifen), or both drugs. The songs of both flutamide- and tamoxifen-treated birds were extremely disrupted relative to normal controls in terms of the stereotypy and acoustic quality of individual note production, as well as stereotypy of the temporal structure of the song phrase. We did not discern any differences in the pattern of behavioral disruption between birds that were treated with either flutamide, tamoxifen, or a combination of both drugs. Flutamide treatment resulted in a reduced size of two forebrain nuclei that are known to play some role unique to early phases of song learning [lateral magnocellular nucleus of the anterior neostriatum (IMAN) and area X (X)], but did not affect the size of two song-control nuclei that are necessary for normal song production in adult birds [caudal nucleus of the ventral hyperstriatum (HVc) and robust nucleus of the archistriatum (RA)]. In contrast, treatment with tamoxifen did not result in any changes in the size of song-control nuclei relative to normal controls, and it blocked the effects of flutamide on the neural song-control system in birds that were treated with both drugs. Castration and antisteroid treatment exerted no deleterious effects on the quality of song behavior in adult birds, indicating that gonadal hormones are necessary for the development of normal song behavior during a sensitive period.

Aging↗

PubMed1992

Matters of life and death in the songbird forebrain.

Male zebra finches learn a specific vocal pattern during a restricted period of development. They produce that song in stereotyped form throughout adulthood, and are unable to learn new song patterns. Development of the neural substrate for song learning and behavior is delayed relative to other brain regions, and neural song-control circuits undergo dramatic changes during the period of vocal learning due to both loss of neurons as well as incorporation of newly generated neurons. In contrast, canaries do learn new song patterns in adulthood and modify their vocal repertoires each breeding season. Adult canaries also maintain a large population of dividing cells in the ependymal zone of the telencephalon, and vast numbers of newly generated neurons migrate out to become incorporated into functional circuits and replace older neurons. We review the relationships between cellular and behavioral aspects of song learning in both zebra finches and canaries, as well as the role of gonadal hormones in regulating diverse aspects of the song-control system.

Animals↗

PubMed1991

Testosterone and the incidence of hormone target cells in song-control nuclei of adult canaries.

Adult male canaries learn to produce high-amplitude complex courtship songs each breeding season, whereas females do not, and brain nuclei involved with the production of song behavior are much larger in breeding males than in nonbreeding males or females (Nottebohm, 1980, 1981). However, treatment of adult females with testosterone (T) causes them to produce male-like song and stimulates pronounced growth of some song-control brain nuclei such as the caudal nucleus of the ventral hyperstriatum (HVc). We reexamined the effects of T on song-control nuclei in deafened birds. In order to examine whether the pattern of hormone accumulation varies as a function of circulating testosterone levels we described the distribution of testosterone-concentrating cells in HVc and the magnocellular nucleus of the anterior neostriatum (MAN) in hearing adult male, female, and T-treated female canaries, as well as in deaf T-treated and untreated females. In contrast to our previous findings (Bottjer, Schoonmaker, and Arnold, 1986a), we observed no tendency in this study for testosterone-induced growth of HVc to be attenuated in deafened birds. There was no difference between deaf and hearing birds in the incidence of labeled cells within HVc. We also observed no sex or hormone-induced differences in the percentage of hormone-concentrating cells in HVc: normal females have approximately the same proportion of hormone target cells as do males and T-treated females. However, males normally have many more neurons in HVc than do control females, and systemic exposure to testosterone induces a pronounced increase in the number of HVc neurons of adult females. Therefore, the absolute number of hormone target cells in HVc is likely to be much greater in males and T-treated females than in normal females. As in HVc, there were no differences among groups in the proportion of labeled cells within lateral MAN (IMAN), a nucleus that has been implicated in song learning (Bottjer, Miesner and Arnold, 1984). In contrast, the incidence of hormone target cells in medial MAN (mMAN) did vary as a function of hormonal condition: although mMAN of normal females is rarely visible in Nissl-stained sections and cells in this region are not hormone labeled, mMAN is clearly visible in Nissl-stained sections of males and T-treated females and contains many hormone-labeled cells. This testosterone-induced change in the phenotype of mMAN cells suggests a possible role for mMAN in learned song behavior.

Animals↗

PubMed1991

Adenohypophysectomy in the zebra finch.

Castration and replacement of gonadal steroids have been used extensively in order to examine the hormonal regulation of song and sexual behaviors in passerine birds. However, recent studies have reported that levels of gonadal hormones may remain high following castration. In order to circumvent this problem, adenohypophysectomy might be advantageous. In this study we describe a technique for removing the anterior pituitary gland in a small passerine species (the zebra finch, Poephila guttata) using a parapharyngeal approach. The completeness of the adenohypophysectomy in individual male and female birds was examined by measuring gonadal weights as well as plasma levels of luteinizing hormone. The results indicate that this technique can be successfully applied to zebra finches. Removal of the anterior pituitary gland may represent a more effective means than gonadectomy for lowering circulating levels of gonadal hormones.

Animals↗

PubMed1991

Chronic testosterone treatment impairs vocal learning in male zebra finches during a restricted period of development.

To study the effects of chronic exposure to testosterone on song behavior development, we administered various amounts of testosterone to juvenile male zebra finches during different periods of song acquisition. We report that testosterone exposure during development profoundly impairs song learning in juvenile males. The effects of the hormone do not seem to be dose related but vary according to the period of life during which testosterone is administered. Exposure to testosterone starting before day 40 and lasting until adulthood decreases the number of syllables in the birds' repertoire and increases the number of phrases per bout of singing. In addition to these changes in the "syntactical" features of song, acoustic abnormalities are also present in the song syllables of males that begin to receive testosterone during the first month of life. Administration of testosterone during only the first 3 weeks of life produces acoustic abnormalities but has no effect on repertoire size or bout structure. Birds receiving the hormone between 20 and 40 d of age develop both acoustic abnormalities and a reduced repertoire size, but their song bouts contain a normal number of song phrases. Exposure to testosterone starting on day 40 produce no behavioral abnormalities. These results indicate that normal song development requires a period of low levels of circulating testosterone and also provide support for the idea that vocal learning entails a progressive sequence of events.

Aging↗

PubMed1989

Axonal connections of a forebrain nucleus involved with vocal learning in zebra finches.

Connections of a telencephalic vocal-control nucleus, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), were studied in adult male zebra finches. Anterograde transport of horseradish peroxidase (alone or conjugated to wheat germ agglutinin) revealed that neurons in lMAN project to another forebrain song-control nucleus, the robust nucleus of the archistriatum (RA). RA is known to project onto the hypoglossal motor neurons that innervate the vocal organ. Retrograde transport of HRP from lMAN labeled a large thalamic nucleus, the medial portion of the dorsolateral nucleus of the thalamus (DLM). DLM in turn receives input from another nucleus of the song-control system, area X of the parolfactory lobe. We confirmed results of previous studies showing that area X receives a projection from the ventral area of Tsai (AVT) in the midbrain. In addition, we replicated results of previous experiments with canaries showing that the song-control nucleus HVc (caudal nucleus of the ventral hyperstriatum) receives input from three sources: the medial magnocellular nucleus of the anterior neostriatum (mMAN), the interfacial nucleus (NIf), and the uvae-form nucleus (Uva) of the thalamus. HVc neurons project to area X and to RA. In summary, there is a path from AVT in the midbrain, to area X, to DLM, and then to lMAN; HVc projects to X and hence indirectly to lMAN. We do not yet know the afferent connections of AVT. Thus, lMAN receives indirect input from a variety of other sources, including other regions known to be involved with vocal control.

Animals↗

PubMed1989

Cell death during development of a forebrain nucleus involved with vocal learning in zebra finches.

Lateral MAN (magnocellular nucleus of the anterior neostriatum) is a forebrain nucleus that is known to be importantly involved with vocal learning in juvenile male zebra finches only during a restricted period of the learning process: lesions of lMAN completely disrupt song behavior in zebra finches prior to 50 days of age but have little or no effect in older juvenile or adult birds. The development of lMAN, as of other song-control regions, is delayed until the time that song behavior is being learned. Lateral MAN undergoes a substantial loss of neurons between 25 and 55 days of age, a time that encompasses initial stages of vocal production as well as the interval during which lMAN lesions become ineffective. In this study, we measured both the time course of neuronal loss and the incidence of pyknotic cells within lMAN during the period of cell loss. There is a pronounced loss of neurons from lMAN between 20 and 35 days, after which the adult number of neurons is established. The incidence of pyknosis is greatest at 20 days, around the time when the loss of live cells is also most pronounced, suggesting that the loss of neurons from lMAN is attributable to cell death. The loss of neurons occurs well before lesions of lMAN become ineffective in disrupting vocal behavior. Thus the neurons remaining in lMAN after the period of cell loss apparently undergo a substantial change in function at the time lesions lose effectiveness (about 55-60 days).

Aging↗

PubMed1989

Developmental changes in the cellular composition of a brain nucleus involved with song learning in zebra finches.

Using a double-labeling technique to characterize projection neurons and androgen target cells, we examined ontogenetic changes in the cellular composition of IMAN, a forebrain nucleus that plays an important role in song learning during a restricted period of male zebra finch development. This nucleus undergoes a massive loss of neurons during the time of song acquisition. We report that during the period of cell loss in IMAN, neither the property of projecting to an efferent target nor the ability to concentrate androgens is able to spare neurons from ontogenetic cell death. Furthermore, we report that, at the time when IMAN ceases to influence song production, a large proportion of androgen-sensitive cells that do not make an efferent projection lose the ability to accumulate androgens.

Androgens↗

PubMed1988

Joint hormonal and sensory stimulation modulate neuronal number in adult canary brains.

Treatment of adult female canaries with testosterone (T) causes them to produce male-typical vocalizations and results in striking growth of brain nuclei that control song behavior (Nottebohm, 1980). The song-control nucleus HVc (caudal nucleus of the ventral hyperstriatum) contains cells that concentrate testosterone or its metabolites, suggesting that steroid hormones may induce the growth of HVc directly by regulating the expression of specific genes in those HVc neurons that have steroid receptors. However, we have previously provided evidence that is inconsistent with the idea that steroids promote growth of HVc solely via a direct action on hormone receptors: testosterone treatment of deafened adult females results in very little growth of HVc, relative to T-treated hearing birds (Bottjer et al., 1986b). Thus, birds in the former group undergo very little overall growth of HVc despite high circulating levels of hormone. We show here that the slightly increased size of HVc in T-treated deaf birds is attributable to an increase in neuronal spacing; the greatly increased size of HVc in T-treated hearing birds is due to an increase in neuronal number as well as spacing. There was virtually no increase in number of HVc neurons in T-treated deafened birds relative to control groups, whereas T-treated hearing birds showed a marked increase in neuron number. The song-control nucleus RA (robust nucleus of the archistriatum), which receives direct afferent input from HVc, also increases in size in response to testosterone treatment. However, the volume of RA increases in both hearing and deafened birds; this increase is primarily due to an increase in neuronal spacing as well as a small increase in neuron number. These results demonstrate that the number of neurons in a specific vocal-control nucleus (HVc) can change dramatically in adult canaries and suggest that some synergistic action of hormonal and sensory stimulation is necessary to induce such a change.

Acoustic Stimulation↗

PubMed1987

Ontogenetic changes in the pattern of androgen accumulation in song-control nuclei of male zebra finches.

The present study examines the development of androgen accumulation in cells of two brain nuclei that are involved in controlling vocal behavior in zebra finches (Poephila guttata). HVc (caudal nucleus of the ventral hyperstriatum) is involved with vocal production in adult birds, and MAN (magnocellular nucleus of the anterior neostriatum) is involved with the initial ability to learn song. In both of these nuclei there is an increase in the proportion of cells that are labeled by systemic injections of tritiated dihydrotestosterone in juvenile male zebra finches during the time when production of song is becoming stereotyped (25-60 days). Within MAN there is an overall loss of cells during this time, such that the absolute number of androgen target cells in MAN remains at a constant level. However, it does not appear to be the case that unlabeled cells are selectively lost from MAN. Rather it appears that both labeled and unlabeled cells are lost, and the absolute number of labeled cells is maintained at a constant level via recruitment of additional labeled cells from the unlabeled population (i.e., some MAN cells that are unlabeled in young birds become labeled in older birds). In line with this hypothesis, there is a large increase in the density of labeling in individual MAN cells, indicating that these cells have an enhanced ability to concentrate androgen. In contrast to the situation in MAN, there is an increase in the overall number of cells within HVc during this time; this increase in total cell number combines with the increased proportion of labeled cells such that the absolute number of androgen target cells in HVc increases threefold. The ability of individual HVc cells to accumulate androgen remains constant. The relationship of these changes in the pattern of androgen accumulation to other aspects of neural and behavioral development related to song in zebra finches are discussed.

Age Factors↗

PubMed1986

Changes in neuronal number, density and size account for increases in volume of song-control nuclei during song development in zebra finches.

The caudal nucleus of the ventral hyperstriatum (HVc) and the robust nucleus of the archistriatum (RA) are two anatomically discrete brain regions that are known to be involved with song production in adult passerine birds. Both the HVc and RA increase greatly in volume during a restricted period of song development in male zebra finches, while brain regions not involved with song control show little or no increase in size. We report here that the increased volume of the HVc is attributable to an increase in the number of neurons during this period of song learning, whereas the growth of the RA is due to an increase in the somal size of neurons and a decrease in neuronal density. The pattern of results described is consistent with the idea that the HVc matures prior to the RA, and that the development of the RA may depend on the ingrowth of axons from the HVc and other song-control regions.

Animals↗

PubMed1986

Auditory and hormonal stimulation interact to produce neural growth in adult canaries.

Gonadal hormones can produce striking behavioral and neural plasticity in adult organisms. For example, systemic administration of testosterone to adult female canaries induces the development of male-typical song behavior and results in a striking increase in the size of brain nuclei that are known to be involved with song control. The mechanism whereby androgens produce such neural plasticity is not known, although it has seemed likely that growth-promoting effects of androgens are due to a direct induction of protein synthesis in cells containing hormone receptors (following activation of specific genes by the hormone-receptor complex). In this experiment we have examined the trophic effect of testosterone in the song-control nucleus HVc (caudal nucleus of the ventral hyperstriatum), which has been shown to contain androgen-concentrating cells as well as neurons that are especially responsive to conspecific song. We report here that testosterone administration increases the volume of HVc in hearing adult female canaries only; testosterone-induced growth of HVc is greatly attenuated in birds that are deprived of auditory stimulation via deafening. Thus, testosterone treatment alone is not a sufficient stimulus for neural growth in HVc. This result suggests that testosterone does not stimulate growth solely via a direct action on hormone receptors in HVc, but rather that testosterone and sensory stimulation can act synergistically to produce structural plasticity in the adult brain.

Acoustic Stimulation↗

PubMed1986

Sexual dimorphisms in the neural vocal control system in song birds: ontogeny and phylogeny.

Sex differences in the neural song system in oscine song birds develop in response to estradiol secreted during early periods of development. Estradiol produces sex differences in cell number and in the proportion of cells which are steroid targets. The pattern of development of these sex differences varies in different brain regions, suggesting that the mechanisms of estradiol regulation of neural development may also vary. The magnitude of sexual dimorphism in the neural song system varies across species, and is generally correlated with the magnitude of sexual dimorphism in vocal ability. Large species differences in neural structure can potentially be explained by small differences in the ontogenetic pattern of estradiol secretion, as is suggested by studies of neural development.

Animals↗

PubMed1985

Ontogeny of brain nuclei controlling song learning and behavior in zebra finches.

An anatomically discrete system of interconnected brain nuclei controls production of learned song patterns in adult male zebra finches (Poephila guttata). The corresponding nuclei in females, who do not sing, are greatly reduced in volume. Cells in some telencephalic song-control nuclei accumulate androgens, and male nuclei contain a much higher proportion of hormone-concentrating cells than do female nuclei. The main purpose of this experiment was to examine the normal ontogeny of the total volume of various telencephalic nuclei that have been directly or indirectly implicated in song learning and behavior in male zebra finches. In addition, the corresponding nuclei of age-matched females were examined. The major findings were as follows: the volumes of the caudal nucleus of the ventral hyperstriatum (HVc), the robust nucleus of the archistriatum (RA), and area X increased sharply in males between 12 and 53 days of age, whereas brain regions not involved with song control increased much less. Increases in the size of HVc occurred prior to those in RA and area X. Previous studies have shown that males are learning the auditory and motor characteristics of song during this time. In contrast, the volume of the magnocellular nucleus of the anterior neostriatum (MAN) decreased precipitously in males between 25 and 53 days. Measurements of neuron density and soma size demonstrated that this decreased volume is attributable to a loss of greater than 50% of the neurons in MAN. We have previously shown that lesions of MAN during this time completely disrupt song development. The volumes of HVc and RA were smaller in females than in males at all ages studied. Between 12 and 25 days the volumes of female HVc and RA increased less than brain regions not involved with song control. Female HVc and RA decreased slightly in volume between 25 and 53 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗