BDNF increases BrdU-IR cells in the injured adult zebra finch hippocampus.

Steroid-mediated cell proliferation, differentiation, and survival can be triggered by learning, experience, and brain injury. In the uninjured canary song system, testosterone induces cell proliferation that is blocked by an antibody to brain-derived neurotrophic factor (BDNF). However, little is known with regard to the effects of neurotrophic factors on injury-induced cell proliferation and incorporation. To address this, adult male zebra finches received bilateral hippocampal lesions by infusing saline into one hemisphere and BDNF into the other. BrdU (2-bromo-5-deoxyuridine) was then injected to label mitotic cells. A greater number of BrdU-immunoreactive (BrdU-IR) cells were observed in the BDNF-treated hemisphere in the hippocampus, but not in the septum or stem cell-rich subventricular zone, indicating that BDNF promoted localized cell proliferation and incorporation at the injury site only.

Aromatase expression and cell proliferation following injury of the adult zebra finch hippocampus.

Estrogens can be neuroprotective following traumatic brain injury. Immediately after trauma to the zebra finch hippocampus, the estrogen-synthetic enzyme aromatase is rapidly upregulated in astrocytes and radial glia around the lesion site. Brain injury also induces high levels of cell proliferation. Estrogens promote neuronal differentiation, migration, and survival naturally in the avian brain. We suspect that glia are a source of estrogens promoting cell proliferation after neural injury. To explore this hypothesis, we examined the spatial and temporal relationship between glial aromatase expression and cell proliferation after neural injury in adult female zebra finches. Birds were ovariectomized and given a blank implant or one filled with estradiol; some birds were also administered an aromatase inhibitor or vehicle. All birds received penetrating injuries to the right hippocampus. Twenty-four hours after lesioning, birds were injected once with BrdU to label mitotically active cells and euthanized 2 h, 24 h, or 7 days later. The brains were processed for double-label BrdU and aromatase immunocytochemistry. Injury-induced glial aromatase expression was unaffected by survival time and aromatase inhibition. BrdU labeling was significantly reduced at 24 h by ovariectomy and by aromatase inhibition; effects were partially reversed by E2 replacement. Irrespective of ovariectomy, the densities of aromatase immunoreactive astrocytes and BrdU-labeled cells at known distances from the lesion site were highly correlated. These data suggest that injury-induced glial aromatization may influence the reorganization of injured tissue by providing a rich estrogenic environment available to influence cellular incorporation.

Estrogen mediation of injury-induced cell birth in neuroproliferative regions of the adult zebra finch brain.

Estrogens influence neuronal differentiation, migration, and survival in intact brains. In injured brains, estrogens can also be neuroprotective. In Experiment 1, following a unilateral penetrating injury to the hippocampus (HP), adult female zebra finches were injected once with BrdU to label mitotic cells then sacrificed 2 h, 1 day, or 7 days postinjection. Cell proliferation was dramatically enhanced in the ipsilateral HP, as well as in neuroproliferative areas including the subventricular zone (SVZ) proximal to the injury. This increase was seen at all time points investigated. Ovariectomy (OVX) substantially suppressed proliferation bilaterally especially in the SVZ indicating that gonadal hormones influenced cell proliferation in both the intact and injured hemisphere. To determine if estrogens were directly involved, estrogen was depleted in Experiment 2 through either OVX or administration of the aromatase inhibitor fadrozole (FAD). Birds were implanted with estradiol or blank followed 2 weeks later by a unilateral penetrating lesion to the HP. Injury-induced substantial proliferation, which was again significantly suppressed bilaterally in both OVX and FAD birds. Estrogen replacement reversed this effect in FAD but not OVX birds therefore the suppression following OVX may be due in part to nonestrogenic influences. Suppression of cell birth in FAD birds was indeed due to the removal of endogenous sources of estrogen. Results therefore indicate that estrogens are directly involved in the brain's response to injury and may be acting to provide a rich environment for the production and perhaps protection of new cells.

Avian brains and a new understanding of vertebrate brain evolution.

We believe that names have a powerful influence on the experiments we do and the way in which we think. For this reason, and in the light of new evidence about the function and evolution of the vertebrate brain, an international consortium of neuroscientists has reconsidered the traditional, 100-year-old terminology that is used to describe the avian cerebrum. Our current understanding of the avian brain - in particular the neocortex-like cognitive functions of the avian pallium - requires a new terminology that better reflects these functions and the homologies between avian and mammalian brains.

Radial glia express aromatase in the injured zebra finch brain.

Estrogens have neurotrophic and neuroprotective properties. The synthesis of estrogen occurs via the expression of aromatase. Previous studies have shown that injury to the vertebrate brain results in a rapid and dramatic up-regulation of aromatase expression in astrocytes around the lesion. As part of experiments examining injury-induced glial aromatization, we identified aromatase in radial glia of the zebra finch brain. Adult female zebra finches received a penetrating injury to the right hippocampus. Twenty-four hours after lesioning, birds were administered bromodeoxyuridine (BrdU) and sacrificed 2 hours, 1 day, or 7 days later. We determined the distribution of aromatase and BrdU labeling by using immunocytochemistry. Radial aromatase was localized to cells lining the lateral ventricle adjacent to the lesioned hippocampus. Injury also induced a dramatic accumulation of newly generated cells labeled with BrdU around the lesion. BrdU labeling was strongly associated with aromatase-positive radial fibers, suggesting the migration of newly generated cells along these fibers. In the songbird brain, estrogen supports neuronal recruitment and promotes the survival and addition of new neurons. The presence of aromatase in radial glia provides a mechanism of estrogen delivery to postmitotic cells. Radial aromatization may be a key feature in the repair of the vertebrate brain following neural injury.

Revised nomenclature for avian telencephalon and some related brainstem nuclei.

The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names. Revisions for the brainstem focused on vocal control, catecholaminergic, cholinergic, and basal ganglia-related nuclei. For example, the Forum recognized that the hypoglossal nucleus had been incorrectly identified as the nucleus intermedius in the Karten and Hodos (1967) pigeon brain atlas, and what was identified as the hypoglossal nucleus in that atlas should instead be called the supraspinal nucleus. The locus ceruleus of this and other avian atlases was noted to consist of a caudal noradrenergic part homologous to the mammalian locus coeruleus and a rostral region corresponding to the mammalian A8 dopaminergic cell group. The midbrain dopaminergic cell group in birds known as the nucleus tegmenti pedunculopontinus pars compacta was recognized as homologous to the mammalian substantia nigra pars compacta and was renamed accordingly; a group of gamma-aminobutyric acid (GABA)ergic neurons at the lateral edge of this region was identified as homologous to the mammalian substantia nigra pars reticulata and was also renamed accordingly. A field of cholinergic neurons in the rostral avian hindbrain was named the nucleus pedunculopontinus tegmenti, whereas the anterior nucleus of the ansa lenticularis in the avian diencephalon was renamed the subthalamic nucleus, both for their evident mammalian homologues. For the basal (i.e., subpallial) telencephalon, the actual parts of the basal ganglia were given names reflecting their now evident homologues. For example, the lobus parolfactorius and paleostriatum augmentatum were acknowledged to make up the dorsal subdivision of the striatal part of the basal ganglia and were renamed as the medial and lateral striatum. The paleostriatum primitivum was recognized as homologous to the mammalian globus pallidus and renamed as such. Additionally, the rostroventral part of what was called the lobus parolfactorius was acknowledged as comparable to the mammalian nucleus accumbens, which, together with the olfactory tubercle, was noted to be part of the ventral striatum in birds. A ventral pallidum, a basal cholinergic cell group, and medial and lateral bed nuclei of the stria terminalis were also recognized. The dorsal (i.e., pallial) telencephalic regions that had been erroneously named to reflect presumed homology to striatal parts of mammalian basal ganglia were renamed as part of the pallium, using prefixes that retain most established abbreviations, to maintain continuity with the outdated nomenclature. We concluded, however, that one-to-one (i.e., discrete) homologies with mammals are still uncertain for most of the telencephalic pallium in birds and thus the new pallial terminology is largely devoid of assumptions of one-to-one homologies with mammals. The sectors of the hyperstriatum composing the Wulst (i.e., the hyperstriatum accessorium intermedium, and dorsale), the hyperstriatum ventrale, the neostriatum, and the archistriatum have been renamed (respectively) the hyperpallium (hypertrophied pallium), the mesopallium (middle pallium), the nidopallium (nest pallium), and the arcopallium (arched pallium). The posterior part of the archistriatum has been renamed the posterior pallial amygdala, the nucleus taeniae recognized as part of the avian amygdala, and a region inferior to the posterior paleostriatum primitivum included as a subpallial part of the avian amygdala. The names of some of the laminae and fiber tracts were also changed to reflect current understanding of the location of pallial and subpallial sectors of the avian telencephalon. Notably, the lamina medularis dorsalis has been renamed the pallial-subpallial lamina. We urge all to use this new terminology, because we believe it will promote better communication among neuroscientists. Further information is available at http://avianbrain.org

The Avian Brain Nomenclature Forum: Terminology for a New Century in Comparative Neuroanatomy.

Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of avian brains have been based are in error, and as a result that terminology promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains. Recognizing this problem, a number of avian brain researchers began an effort to revise the terminology, which culminated in the Avian Brain Nomenclature Forum, held at Duke University from July 18 to 20, 2002. In the new terminology approved at this Forum, the flawed conception that the telencephalon of birds consists nearly entirely of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given names reflecting their now evident homologies. The telencephalic regions that were erroneously named to reflect presumed homology to mammalian basal ganglia were renamed as parts of the pallium, using prefixes that retained most established abbreviations (to maintain continuity with the replaced nomenclature). Details of this meeting and its major conclusions are presented in this paper, and the details of the new terminology and its basis are presented in a longer companion paper. We urge all to use this new terminology, because we believe it will promote better communication among neuroscientists.