Wiley

The marine mollusc Aplysia californica has proved to be a useful preparation for analyzing the development of learning and memory on both behavioral and cellular levels. An important issue in this analysis concerns the anatomical substrate upon which learning is superimposed during development. As a first step in examining this question, in the present study we have determined the number of neurons in all the major central ganglia at each stage during juvenile development, a time when several forms of learning first emerge in Aplysia. We found that a large and highly nonlinear proliferation of neurons occurs during juvenile development, with the greatest increase in cell number occurring during a specific juvenile stage: Stage 12. The neuronal proliferation is system‐wide, occurring in each of the central ganglia simultaneously, suggesting the action of a general developmental signal or trigger (perhaps a hormone). Accompanying the increase in neuron number in Stage 12 there is a large increase in neuropilar volume (150‐fold), which significantly increases the opportunity for synaptic interactions late in juvenile development.

Dopamine (DA) is the only catecholaminergic neurotransmitter in the fruit fly Drosophila melanogaster. Dopaminergic neurons have been identified in the larval and adult central nervous system (CNS) in Drosophila and other insects, but no specific genetic tool was available to study their development, function, and degeneration in vivo. In Drosophila as in vertebrates, the rate‐limiting step in DA biosynthesis is catalyzed by the enzyme tyrosine hydroxylase (TH). The Drosophila TH gene (DTH) is specifically expressed in all dopaminergic cells and the corresponding mutant, pale (ple), is embryonic lethal. We have performed ple rescue experiments with modified DTH transgenes. Our results indicate that partially redundant regulatory elements located in DTH introns are required for proper expression of this gene in the CNS. Based on this study, we generated a GAL4 driver transgene, TH‐GAL4, containing regulatory sequences from the DTH 5′ flanking and downstream coding regions. TH‐GAL4 specifically expresses in dopaminergic cells in embryos, larval CNS, and adult brain when introduced into the Drosophila genome. As a first application of this driver, we observed that in vivo inhibition of DA release induces a striking hyperexcitability behavior in adult flies. We propose that TH‐GAL4 will be useful for studies of the role of DA in behavior and disease models in Drosophila. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 618–627, 2003

Dopamine is an important signaling molecule in the nervous system; it also plays a vital role in the development of diverse non‐neuronal tissues in the fruit fly Drosophila melanogaster. The current study demonstrates that males depleted of dopamine as third instar larvae (via inhibition of the biosynthetic enzyme tyrosine hydroxylase) demonstrated abnormalities in courtship behavior as adults. These defects were suggestive of abnormalities in sensory perception and/or processing. Electroretinograms (ERGs) of eyes from adults depleted of dopamine for 1 day as third instar larvae revealed diminished or absent on‐ and off‐transients. These sensory defects were rescued by the addition of L‐DOPA in conjunction with tyrosine hydroxylase inhibition during the larval stage. Depletion of dopamine in the first or second larval instar was lethal, but this was not due to a general inhibition of proliferative cells. To establish that dopamine was synthesized in tissues destined to become part of the adult sensory apparatus, transgenic lines were generated containing 1 or 4 kb of 5′ upstream sequences from the Drosophila tyrosine hydroxylase gene (DTH) fused to the E. coli β‐galactosidase reporter. The DTH promoters directed expression of the reporter gene in discrete and consistent patterns within the imaginal discs, in addition to the expected expression in gonadal, brain, and cuticular tissues. The β‐galactosidase expression colocalized with tyrosine hydroxylase protein. These results are consistent with a developmental requirement for dopamine in the normal physiology of adult sensory tissues. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 280–294, 2001

Antibodies to human amyloid precursor protein (APP₆₉₅) and beta‐amyloid peptide (Aβ_1‐42) were used to determine timing of amyloidosis in the brain of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages: immature (IM), maturing (MA), sexually mature (SM), and spawning (SP), representing a range of aging from somatically mature but sexually immature to spawning and somatic senescence. In IM fish, immunoreactive (ir) intracellular APP occurred in 18 of 23 brain regions. During sexual maturation and aging, the number of neurons expressing APP increased in 11 of these APP‐ir regions. Aβ‐ir was absent in IM fish, present in seven regions in MA fish, moderately abundant in 15 regions in SM fish, and was most abundant in all brain regions of SP fish exhibiting Aβ‐ir. Intracellular APP‐ir was observed in brain regions involved in sensory integration, olfaction, vision, stress responses, reproduction, and coordination. Intra‐ and extracellular Aβ_1‐42 immunoreactivity (Aβ‐ir) was present in all APP‐ir regions except the nucleus lateralis tuberis (hypothalamus) and Purkinje cells (cerebellum). APP‐ir and Aβ deposition increase during aging. APP‐ir is present in IM fish; Aβ‐ir usually appears first in MA or SM fish and increases in SM fish as does APP‐ir. Extracellular Aβ deposition dramatically increases between SM and SP stages (1–2 weeks) in all fish, indicating an extremely rapid and synchronized process. Rapid senescence observed in pacific salmon could make them a useful model to investigate timing of amyloidosis and neurodegeneration during brain aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 11–20, 2002

Brains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty‐four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for Aβ. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack Aβ; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in Aβ deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with Aβ production, whereas in only two regions did Aβ deposition precede neurodegeneration. This information supports the hypothesis that Aβ deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 21–35, 2002

Accurate song perception is likely to be as important for female songbirds as it is for male songbirds. Male zebra finches (Taeniopygia guttata) show differential ZENK expression to conspecific and heterospecific songs by day 30 posthatch in auditory perceptual brain regions such as the caudomedial nidopallium (NCM) and the caudomedial mesopallium (CMM). The current study examined ZENK expression in response to songs of different qualities at day 45 posthatch in both sexes. Normally reared juvenile zebra finches showed higher densities of immunopositive nuclei in both the dorsal and ventral areas of NCM and CMM (formerly cmHV), but not HA, a visual area, in response to normal song over untutored song or silence. Male and female patterns of ZENK expression did not differ. We next compared responses of birds reared without exposure to normal song (untutored) to those of normally reared birds. Untutored birds did not show higher responses to normal song than to untutored song in the three song perception areas. Furthermore, untutored birds of both sexes showed lower densities of immunopositive nuclei in all four areas than did normally reared birds. In addition, ZENK expression was greater in untutored females than in males in the dorsal portion of NCM and in CMM. Our findings suggest that at least some neural mechanisms of song perception are in place in socially reared female and male finches at an early age. Furthermore, early exposure to song tutors affects responses to song stimuli. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 1175–1182, 2006

We examined the effects of song tutoring on adult song preferences, volume of song‐control brain regions, and activity of auditory brain regions in female house finches (Carpodacus mexicanus). Hand‐reared females were tutored with local songs, foreign songs, or no song. We then examined adult song preferences, determined the Nissl‐defined volume of the song‐control nuclei HVc, Area X, and RA, and compared the number of cells immunoreactive for Zenk protein in the auditory regions NCM and cmHV, following playback of songs heard early in life (Tutor/Playback Match) versus not heard (Tutor/Playback Nonmatch). All hand‐reared birds exhibited preferences for locally recorded song over foreign or heterospecific song. We found no difference in the volume of song‐control nuclei among the three groups. As well, we found no difference in the number of Zenk immunoreactive cells in NCM and cmHV between females in the Tutor/Playback Match group and females in the Tutor/Playback Nonmatch group. Isolate‐reared birds showed greater Zenk immunoreactivity following song playback than either tutored group. Thus, early auditory experience may not play a role in adult geographic song preferences, suggesting that genetic factors can lead to preferences for songs of local dialects. Song tutoring did not influence the size of song‐control regions nor Zenk induction levels following song playback, suggesting that early experience with particular songs does not influence Zenk expression. However, overall greater activation in isolate females in auditory areas suggests that exposure to song early in life may increase the selectivity of Zenk activation to song playback in auditory areas. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 247–258, 2004

Psychological researchers typically distinguish five major domains of individual differences in human behavior: cognitive abilities, personality, social attitudes, psychological interests, and psychopathology (Lubinski, 2000). In this article we: discuss a number of methodological errors commonly found in research on human individual differences; introduce a broad framework for interpreting findings from contemporary behavioral genetic studies; briefly outline the basic quantitative methods used in human behavioral genetic research; review the major criticisms of behavior genetic designs, with particular emphasis on the twin and adoption methods; describe the major or dominant theoretical scheme in each domain; and review behavioral genetic findings in all five domains. We conclude that there is now strong evidence that virtually all individual psychological differences, when reliably measured, are moderately to substantially heritable. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 4–45, 2003

Nicotinic receptors are cation‐ion selective ligand‐gated ion channels that are expressed throughout the nervous system. Most have significant calcium permeabilities, enabling them to regulate calcium‐dependent events. One of the most abundant is a species composed of the α7 gene product and having a relative calcium permeability equivalent to that of NMDA receptors. The α7‐containing receptors can be found presynaptically where they modulate transmitter release, and postsynaptically where they generate excitatory responses. They can also be found in perisynaptic locations where they modulate other inputs to the neuron and can activate a variety of downstream signaling pathways. The effects the receptors produce depend critically on the sites at which they are clustered. Instructive preparations for examining α7‐containing receptors are the rat hippocampus, where they are thought to play a modulatory role, and the chick ciliary ganglion, where they participate in throughput transmission as well as regulatory signaling. Relatively high levels of α7‐containing receptors are found in the two preparations, and the receptors display a variety of synaptic options and functions in the two cases. Progress is starting to be made in understanding the mechanisms responsible for localizing the receptors at specific sites and in identifying components tethered in the vicinity of the receptors that may facilitate signal transduction and downstream signaling. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 512–523, 2002

Stop‐flow techniques were used to examine the rapid axonal transport of norepinephrine in rabbit sciatic nerves. When the midpoint of a nerve incubated in vitro was cooled to 2°C while the remainder was kept at 37°C, norepinephrine accumulated proximal to the cooled region at a rate corresponding to an average transport velocity between 5 and 6 mm/hr in a distal direction. Since only about half of the norepinephrine appeared to be free to move, the mean velocity of the moving fraction was probably twice as great. No norepinephrine accumulated distal to a broad cooled region under conditions in which there would have been a significant accumulation of dopamine‐β‐hydroxylase activity. Therefore, unlike dopamine‐β‐hydroxylase, norepinephrine may not be subject to rapid retrograde transport. When nerves that had been locally cooled for 1.5 hr were rewarmed uniformly to 37°C, a wave of norepinephrine moved exclusively in a distal direction. The peak of this wave moved at a velocity of 12.2 ± 0.5 mm/hr or 293 ± 12 mm/day; the front of the wave moved at about 18 mm/hr. or 430 mm/day; and the tail probably moved faster than 6 mm/hr. This spectrum of velocities was virtually identical to the one displayed by the wave of dopamine‐β‐hydroxylase activity that was generated under the same conditions. Our results are consistent with the conclusion that all axonal structures containing norepinephrine also contain dopamine‐β‐hydroxylase, but they are not consistent with the converse.