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1.  Species differences in the relative densities of D1-like and D2-like dopamine receptor subtypes in the Japanese quail and rats: An in vitro quantitative receptor autoradiography study 
Brain, behavior and evolution  2009;73(2):81-90.
Evidence has accumulated that the regulation of male sexual behavior by dopamine may not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective dopamine receptor agonist, apomorphine (APO) facilitates male sexual behavior in rats but inhibits it in quail. Although the general organization of the dopamine system is similar in birds and mammals, it is possible that the relative distribution and/or density of binding sites is different. We therefore compared the relative densities of D1-like and D2-like receptor subtypes in Japanese quail and rats, with the use of in vitro quantitative receptor autoradiography. Brain sections from 8 male rats and 8 male quail were labeled with [3H]SCH-23390 and [3H]Spiperone. In general we found a systematic species difference in the relative density of D1-like vs. D2-like receptors such that the D2/D1 ratio is higher in quail than in rats in areas well known to be important target sites for dopamine action such as striatal regions. We also uncovered significant differences in the relative density of D1-like and D2-like receptors in brain areas associated with sexual behavior, including the preoptic area, such that there was a greater D2/D1 ratio in quail as compared to rats. This difference may explain the variation in the behavioral effectiveness of APO in rats as compared to quail; with a higher relative density of D2-like receptors in quail, a similar dose of APO would be more likely to activate inhibitory processes in quail than in rats.
doi:10.1159/000209864
PMCID: PMC3522861  PMID: 19321949
dopamine; autoradiography; apomorphine; male sexual behavior; bird
2.  On the Perception of Speech Sounds as Biologically Significant Signals1,2 
Brain, behavior and evolution  1979;16(5-6):330-350.
This paper reviews some of the major evidence and arguments currently available to support the view that human speech perception may require the use of specialized neural mechanisms for perceptual analysis. Experiments using synthetically produced speech signals with adults are briefly summarized and extensions of these results to infants and other organisms are reviewed with an emphasis towards detailing those aspects of speech perception that may require some need for specialized species-specific processors. Finally, some comments on the role of early experience in perceptual development are provided as an attempt to identify promising areas of new research in speech perception.
PMCID: PMC3512094  PMID: 399200
Speech perception; Synthetic speech; Identification; Discrimination; Species-specific acoustic signals; Perceptual development; Feature detectors; Perceptual constancy; Speech mode
3.  Bigger Brains or Bigger Nuclei? Regulating the Size of Auditory Structures in Birds 
Brain, Behavior and Evolution  2004;63(3):169-180.
Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hind-brain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds.
doi:10.1159/000076242
PMCID: PMC3269630  PMID: 14726625
Evolution; Auditory; Neuronal computation; Birds; Allometry
4.  Plasticity of Auditory Medullary-Midbrain Connectivity across Metamorphic Development in the Bullfrog, Rana catesbeiana 
Brain, Behavior and Evolution  2006;69(1):1-19.
On the basis of patterns of anterograde, retrograde, and bi-directional transport of tracers from both the superior olivary nucleus (SON) and the torus semicircularis (TS), we report anatomical changes in brainstem connectivity across metamorphic development in the bullfrog, Rana catesbeiana. In early and late stages of larval development (Gosner stages 25–37), anterograde or bi-directional tracers injected into the SON produce terminal/fiber label in the contralateral SON and in the ipsilateral TS. Between stages 38–41 (deaf period), only sparse or no terminal/fiber label is visible in these target nuclei. During metamorphic climax (stages 42–46), terminal/fiber label reappears in both the contralateral SON and in the ipsilateral TS, and now also in the contralateral TS. Injections of retrograde tracers into the SON fail to label cell bodies in the ipsilateral TS in deaf period animals, mirroring the previously-reported failure of retrograde transport from the TS to the ipsilateral SON during this developmental time. Bilateral cell body label emerges in the dorsal medullary nucleus and the lateral vestibular nucleus bilaterally as a result of SON transport during the late larval period, while cell body label in the contralateral TS emerges during climax. At all larval stages, injections into the SON produce anterograde and retrograde label in the medial vestibular nucleus bilaterally. These data show anatomical stability in some pathways and plasticity in others during larval development, with the most dramatic changes occurring during the deaf period and metamorphic climax. Animals in metamorphic climax show patterns of connectivity similar to that of froglets and adults, indicating the maturation during climax of central anatomical substrates for hearing in air.
doi:10.1159/000095027
PMCID: PMC3257804  PMID: 16912473
Tadpoles; Anurans; Vestibular nucleus complex; Dorsal medullary nucleus; Superior olivary complex; Torus semicircularis; Lipophilic dyes; PHA-L; Cholera toxin; Metamorphosis
5.  Developmental and Regional Patterns of GAP-43 Immunoreactivity in a Metamorphosing Brain 
Brain, Behavior and Evolution  2008;71(4):247-262.
Growth-associated protein-43 is typically expressed at high levels in the nervous system during development. In adult animals, its expression is lower, but still observable in brain areas showing structural or functional plasticity. We examined patterns of GAP-43 immunoreactivity in the brain of the bullfrog, an animal whose nervous system undergoes considerable reorganization across metamorphic development and retains a strong capacity for plasticity in adulthood. Immunolabeling was mostly diffuse in hatchling tadpoles, but became progressively more discrete as larval development proceeded. In many brain areas, intensity of immunolabel peaked at metamorphic climax, the time of final transition from aquatic to semi-terrestrial life. Changes in intensity of GAP-43 expression in the medial vestibular nucleus, superior olivary nucleus, and torus semicircularis appeared correlated with stage-dependent functional changes in processing auditory stimuli. Immunolabeling in the Purkinje cell layer of the cerebellum and in the cerebellar nucleus was detectable at most developmental time points. Heavy immunolabel was present from early larval stages through the end of climax in the thalamus (ventromedial, anterior, posterior, central nuclei). Immunolabel in the tadpole telencephalon was observed around the lateral ventricles, and in the medial septum and ventral striatum. In postmetamorphic animals, immunoreactivity was confined mainly to the ventricular zones and immediately adjacent cell layers. GAP-43 expression was present in olfactory, auditory and optic cranial nerves throughout larval and postmetamorphic life. The continued expression of GAP-43 in brain nuclei and in cranial nerves throughout development and into adulthood reflects the high regenerative potential of the bullfrog’s central nervous system.
doi:10.1159/000127045
PMCID: PMC3257825  PMID: 18431052
Growth-associated protein 43; Plasticity; Metamorphosis; Bullfrog; Midbrain; Forebrain; Cranial nerves
6.  Cell Proliferation in the Forebrain and Midbrain of the Adult Bullfrog, Rana catesbeiana 
Brain, Behavior and Evolution  2007;71(1):41-53.
The distribution of proliferating cells in the midbrain, thalamus, and telencephalon of adult bullfrogs (Rana catesbeiana) was examined using immunohistochemistry for the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) and DNA dot-blotting. At all time points examined (2 to 28 days post-injection), BrdU-labeled cells were located in ventricular zones at all levels of the neuraxis, but with relatively more label around the telencephalic ventricles. Labeled cells, some showing profiles indicative of dividing and migrating cells, were present in brain parenchyma from 7 to 28 days post-injection. These labeled cells were particularly numerous in the dorsal and ventral hypothalamus, preoptic area, optic tectum, and laminar and principal nuclei of the torus semicircularis, with label also present, but at qualitatively reduced levels, in thalamic and telencephalic nuclei. Double-label immunohistochemistry using glial and early neural markers indicated that gliogenesis and neurogenesis both occurred, with new neurons observed particularly in the hypothalamus, optic tectum, and torus semicircularis. In all brain areas, many cells not labeled with BrdU were nonetheless labeled with the early neural marker TOAD-64, indicating that these cells were postmitotic. Incorporation of DNA measured by dot-blotting confirms the presence of DNA synthesis in the forebrain and brainstem at all time points measured. The pattern of BrdU label confirms previous experiments based on labeling with 3H-thymidine and proliferating cell nuclear antigen showing cell proliferation in the adult ranid brain, particularly in hypothalamic nuclei. The consistent appearance of new cells in the hypothalamus of adult frogs suggests that proliferative activity may be important in mediating reproductive behaviors in these animals.
doi:10.1159/000108610
PMCID: PMC3256745  PMID: 17878717
Cell proliferation; Neurogenesis; Gliogenesis; Amphibians; Bullfrog
7.  Phenotypic Specification of Hindbrain Rhombomeres and the Origins of Rhythmic Circuits in Vertebrates 
Brain, behavior and evolution  1997;50(Suppl 1):3-16.
This essay considers the ontogeny and phylogeny of the cranial neural circuitry producing rhythmic behaviors in vertebrates. These behaviors are characterized by predictable temporal patterns established by a neuronal network variously referred to as either a pacemaker, neural oscillator or central pattern generator. Comparative vertebrate studies have demonstrated that the embryonic hindbrain is divided into segmented compartments called rhombomeres, each of which gives rise to a distinct complement of cranial motoneurons and, as yet, unidentified populations of interneurons. We now propose that novel rhythmic circuits were innovations associated with the adoption of cardiac and respiratory pumps during the protochordate-vertebrate transition. We further suggest that the pattern-generating circuits of more recent innovations, such as the vocal, electromotor and extraocular systems, have originated from the same Hox gene-specified compartments of the embryonic hindbrain (rhombomeres 7–8) that gave rise to rhythmically active cardiac and respiratory circuits. Lastly, we propose that the capability for pattern generation by neurons originating from rhombomeres 7 and 8 is due to their electroresponsive properties producing pacemaker oscillations, as best typified by the inferior olive which also has origins from these same hindbrain compartments and has been suggested to establish rhythmic oscillations coupled to sensorimotor function throughout the neuraxis of vertebrates.
PMCID: PMC3023276  PMID: 9217990
Rhombomeres; Hindbrain; Hox genes; Pacemaker; Oscillator; Vocalization; Electromotor; Oculomotor; Inferior olive; Cerebellum; Teleost
8.  Distribution of 2-[125I]iodomelatonin Binding in the Brain of Mexican Free-Tailed Bats (Tadarida brasiliensis) 
Brain, behavior and evolution  2009;73(1):16-25.
The neurohormone melatonin is an important signal for both time of day and time of year in many seasonally breeding animals. High densities of melatonin receptors have been found in the suprachiasmatic nucleus, median eminence, and the pituitary gland in almost all mammals investigated so far, and lower densities of melatonin receptors have also been localized to other brain regions varying in a species-specific fashion. Because species-specific differences in receptor distributions have been correlated with differences in behavior and ecology, a comparative study of how melatonin receptors are distributed in vertebrate brains can be useful to the understanding of the functional organization of neural circuits controlling daily and seasonal behaviors. In this study, we localized and characterized melatonin binding sites in the brain of the Mexican free-tailed bat (Tadarida brasiliensis) using in vitro autoradiography with 2-[125I]iodomelatonin. Tadarida brasiliensis is a nocturnal insectivorous mammal that seasonally migrates, reproduces once a year, and exhibits documented sexual dimorphisms in seasonal reproductive behaviors, most notably in courtship vocalizations. Prominent 2-[125I]iodomelatonin binding was found in the median eminence, suprachiasmatic nuclei, and hippocampus, similar to that observed in other mammals. High densities of binding were also localized to structures of the basal ganglia, including the caudate nucleus, putamen, and nucleus accumbens, a feature commonly observed in songbirds but not in mammals. Saturation analysis indicated that the observed binding sites had an affinity for melatonin typical of the binding properties for the Mel1a receptor subtype. We conclude that melatonin receptor distributions in the Mexican free-tailed bat brain appear to show similarities with the reproductive and circadian systems of other mammals and the basal ganglia of songbirds.
doi:10.1159/000202987
PMCID: PMC2825557  PMID: 19223684
Bats; Basal ganglia; Hippocampus; Melatonin; Suprachiasmatic nucleus
9.  Early ontogeny of the olfactory organ in a basal actinopterygian fish: Polypterus 
Brain, behavior and evolution  2009;73(4):259-272.
The present study employed light and electron microscopic methods to investigate the ontogenetic origin of the olfactory organ in bichirs (Cladistia: Polypteridae) and explore its evolution among osteichthyans. In former studies we demonstrated that in teleosts a subepidermal layer gives rise to the olfactory placode which in turn builds all types of olfactory cells (basal, receptor, supporting, ciliated non-sensory cells). In contrast, the olfactory placodes in sturgeons (Chondrostei: Acipenseridae) as well as in the clawed frog Xenopus laevis (Anura: Pipidae) originate from two different layers. Receptor neurons derive from cells of the subepidermal (sensory) layer and supporting cells from epidermal cells. As sturgeons and amphibians in some characters show a more primitive condition than teleosts, we extended our study to Polypterus to allow for an approach at the basic osteichthyan pattern. In Polypterus, an internal lumen occurs in early ontogenetic stages surrounded by the epithelium of the olfactory placode. Two different populations of supporting cells follow one another: a primary population derives from the subepidermal layer. Later supporting cells develop from epidermal cells by transdifferentiation. The primary opening of the internal lumen to the exterior develops by invagination from the epidermal surface and simultaneously by a counter-directed process of cell dissociation and fragmentation inside the olfactory placode. Our results indicate the following features to be plesiomorphic actinopterygian character states: The primary olfactory pit (prospective olfactory cavity) is formed by invagination of the epidermal and the subepidermal layer (as in Acipenser and Xenopus). The incurrent and excurrent nostrils derive from a single primary opening which elongates and is then separated by an epidermal bridge into the two external openings (as in Acipenser and many teleosts). The olfactory epithelium derives from an epidermal and a subepidermal layer (as in Acipenser and Xenopus). Apomorphic (derived actinopterygian) features are: (1) an internal lumen as primordium of the future olfactory chamber; (2) a subepidermal layer gives rise to the olfactory epithelium and its constituents (Polypterus and teleosts). As to the origin of the olfactory supporting cells in Polypterus we assume a combination of plesiomorphic and apomorphic characters. We conclude that Acipenser and Xenopus exhibit the most widely distributed features among basal osteognathostomes and thus ancestral character states in the development of the olfactory organs.
doi:10.1159/000228162
PMCID: PMC2746032  PMID: 19590178
Actinopterygii; Cladistia; Olfactory Placode; Ontogeny; Phylogeny; Ultrastructure
10.  Exploring the Origins of the Human Brain through Molecular Evolution 
Brain, behavior and evolution  2008;72(2):168-177.
The emergence of the human brain is one of evolution’s most compelling mysteries. With its singular importance and astounding complexity, understanding the forces that gave rise to the human brain is a major undertaking. Recently, the identification and publication of the complete genomic sequence of humans, mice, chimpanzees, and macaques has allowed for large-scale studies looking for the genic substrates of this natural selection. These investigations into positive selection, however, have generally produced incongruous results. Here we consider some of these studies and their differences in methodologies with an eye towards how they affect the results. We also clarify the strengths and weaknesses of each of these approaches and discuss how these can be synthesized to develop a more complete understanding of the genetic correlates behind the human brain and the selective events that have acted upon them.
doi:10.1159/000151476
PMCID: PMC2700753  PMID: 18836262
Hominid; Primate; Human evolution; Brain evolution; Neurogenetics; Molecular evolution
11.  Auditory sensitivity of an acoustic parasitoid (Emblemasoma sp., Sarcophagidae, Diptera) and the calling behavior of potential hosts 
Brain, behavior and evolution  2008;72(1):16-26.
Using field broadcasts of model male calling songs, we tested whether Tibicen pruinosa and T. chloromera (Homoptera: Cicadidae) are candidate hosts for acoustic parasitoid flies. The model calling song of T. pruinosa attracted 90% of the flies (Sarcophagidae: Emblemasoma sp.; all larvapositing females) when broadcast simultaneously with the model T. chloromera song, a phonotactic bias reconfirmed in single song playbacks. In paired broadcasts of model T. pruinosa songs with different relative amplitudes (3 dB or 6 dB), significantly more flies were attracted to the more powerful song, a result consistent with the responses predicted by a model proposed by Forrest and Raspet [1994]. Using intracellular recordings and dye injections, we characterized the sensitivity of auditory units in sound-trapped flies. Intracellular recordings from six auditory units (5 interneurons, 1 afferent) revealed best sensitivity for frequencies near 3-4 kHz, matching the predominant spectral components of the calling songs of both species of cicada. Interestingly, although flies could be attracted to T. pruinosa broadcasts throughout the day, hourly censuses of singing males revealed that calling occurred exclusively at dusk. Furthermore, the duration of the dusk chorus in T. pruinosa was significantly shorter than the midday chorus of the less attractive song of T. chloromera. We propose that the tight temporal aggregation of the dusk chorus time could function to reduce risk from attracted parasitoids.
doi:10.1159/000139458
PMCID: PMC2644656  PMID: 18560209
Cicada; Diel Behavior; Parasitoid; Cricket; Chorus; Tibicen; Ormia; Emblemasoma; phonotaxis; interneuron; frequency tuning
12.  The Eye of the Laboratory Mouse Remains Anatomically Adapted for Natural Conditions 
Brain, behavior and evolution  2005;67(1):39-52.
Evolutionary effects of domestication have been demonstrated for several body systems, including the eye, and for several vertebrate species, including the mouse. Given the importance of the laboratory mouse to vision science, we wished to determine whether the anatomical and histological features of the eyes of laboratory mice are distinct from those of their naturally adapted, wild counterparts. We measured dimensions and masses of whole eyes and lenses from a wild population plus three inbred strains (C57BL/6J, NZB/BINJ, and DBA/1J) of the house house, Mus musculus, as well as wild and outbred laboratory-domesticated stock of the deer mouse, Peromyscus maniculatus. Histological preparations from these eyes were used to determine outer nuclear layer thickness, linear density of the ganglion cell layer, and for indirect immunofluorescence evaluation of cone opsin expression. For all of these traits, no statistically significant differences were found between any laboratory strain and its wild counterpart. The evolutionary effects of domestication of mice therefore do not include changes to the eye in any variable measured, supporting the continued use of this animal as a model for a naturally adapted visual system.
doi:10.1159/000088857
PMCID: PMC2582157  PMID: 16219997
Mouse; Eye; Photoreceptor; Ganglion cell; Evolution; Domestication; Vision; Mammal
13.  Social Signals Regulate Gonadotropin-Releasing Hormone Neurons in the Green Treefrog 
Brain, behavior and evolution  2004;65(1):26-32.
Animals coordinate their physiological state with external cues to appropriately time reproduction. These external cues exert effects through influences on the gonadotropin-releasing hormone neurons (GnRH), at the apex of the hypothalamus-pituitary-gonad (HPG) axis. In green treefrogs, mating calls are important regulators of reproductive behavior and physiology. Reception of mating calls causes an increase in androgen levels, and androgens promote the production of mating calls, demonstrating a mutual influence between the communication and endocrine systems. In order to investigate the central nervous system correlates of social regulation of the HPG axis in green treefrogs, we exposed males to a mating chorus or a control stimulus (tones), counted the resulting number of septopreoptic GnRH-immunoreactive cells (GnRH-ir), and measured changes in plasma androgens. We found that reception of the mating chorus caused an increase in the number of GnRH-ir cells. As previously shown, we also found that the reception of the mating chorus resulted in higher androgen levels, suggesting that the higher GnRH-ir cell number represents increased GnRH production and release. We suggest that mating calls are an important supplementary cue that promotes GnRH production and release within the context of GnRH regulation by seasonal cues. Previous studies have proposed a neuroanatomical link between the anuran auditory system and GnRH neurons. Our results demonstrate a functional role for this proposed sensory-endocrine circuit, and show for the first time an influence of acoustic signals on GnRH neurons.
doi:10.1159/000081108
PMCID: PMC2581501  PMID: 15489562
GnRH; Amphibian; Treefrog; Acoustic communication; Androgens; Supplementary reproductive cue
14.  Characterization of the Shark Myelin Po Protein 
Brain, behavior and evolution  2008;72(1):48-58.
Myelin, the insulating sheath made by extensive plasma membrane wrappings is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations point to it as a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in evolution about 400 million years ago, are the first fully myelinated organisms. In this study we set out to investigate the expression pattern of shark myelin Po as a way of understanding how it might have played a role in the evolution of myelin in the central nervous system. We found that shark have more than two isoforms (32, 28 and 25kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.
doi:10.1159/000145717
PMCID: PMC2574774  PMID: 18635929
15.  Nest of Origin Predicts Adult Neuron Addition Rates in the Vocal Control System of the Zebra Finch 
Brain, behavior and evolution  2008;71(4):263-270.
Neurogenesis and neuronal replacement in adulthood represent dramatic forms of plasticity that might serve as a substrate for behavioral flexibility. In songbirds, neurons are continually replaced in HVC (used as a proper name), a pre-motor region necessary for the production of learned vocalizations. There are large individual differences in HVC neuron addition. Some of this variation is probably due to individual differences in adult experience; however, it is also possible that heritability or experience early in development constrains the levels of adult neuron addition. As a step toward addressing the latter two possibilities, we explored the extent to which nest of origin predicts rates of HVC neuron addition in adult male zebra finches. One month after injections of [3H]-thymidine to mark dividing cells, neuron addition in HVC was found to co-vary among birds that had been nest mates, even when they were housed in different cages as adults. We also tested whether nest mate co-variation might be due to shared adult auditory experience by measuring neuron addition in nest mate pairs after one member was deafened. There were significant differences in neuron addition between hearing and deaf birds but nest mate relationships persisted. These results suggest that variation in genotype and/or early pre- or postnatal experience can account for a large fraction of adult variation in rates of neuron addition. These results also suggest that a major constraint on neurogenesis and the capacity to adjust rates of neuron addition in response to adult auditory experience is established early in development.
doi:10.1159/000127046
PMCID: PMC2574211  PMID: 18431053
Adult neurogenesis; Birdsong; Heritability; Song system
16.  Reproductive Hormones Modify Reception of Species-Typical Communication Signals in a Female Anuran 
Brain, behavior and evolution  2007;71(2):143-150.
In many vertebrates, the production and reception of species-typical courtship signals occurs when gonadotropin and gonadal hormone levels are elevated. These hormones may modify sensory processing in the signal receiver in a way that enhances behavioral responses to the signal. We examined this possibility in female túngara frogs (Physalaemus pustulosus) by treating them with either gonadotropin (which elevated estradiol) or saline and exposing them to either mate choruses or silence. Expression of an activity-dependent gene, egr-1, was quantified within two sub-nuclei of the auditory midbrain to investigate whether gonadotropin plus chorus exposure induced greater egr-1 induction than either of these stimuli alone. The laminar nucleus (LN), a sub-nucleus of the torus semicircularis that contains steroid receptors, exhibited elevated egr-1 induction in response to chorus exposure and gonadotropin treatment. Further analysis revealed that neither chorus exposure nor gonadotropin treatment alone elevated egr-1 expression in comparison to baseline levels whereas gonadotropin + chorus exposure did. This suggests that mate signals and hormones together produce an additive effect so that together they induce more egr-1 expression than either alone. Our previously published studies of female túngara frogs reveal that (1) gonadotropin-induced estradiol elevations also increase behavioral responses to male signals, and (2) reception of male signals elevates estradiol levels in the female. Here, we report data that reveal a novel mechanism by which males exploit female sensory processing to increase behavioral responses to their courtship signals.
doi:10.1159/000111460
PMCID: PMC2572708  PMID: 18032889
Amphibian; Acoustic communication; Midbrain; Gonadotropin; Immediate early genes
17.  Distribution of Corticotropin-releasing factor and Urocortin 1 in the vole brain 
Brain, behavior and evolution  2006;68(4):229-240.
Brain receptor patterns for the corticotropin-releasing factor (CRF) receptors, CRF1 and CRF2, are dramatically different between monogamous and promiscuous vole species, and CRF physiologically regulates pair bonding behavior in the monogamous prairie vole. However, little is known whether species differences also exist in the neuroanatomical distribution of the endogenous ligands for the CRF1 and CRF2 receptors, such as CRF and urocortin-1 (Ucn1). We compared the expression of CRF and Ucn1 in four vole species, monogamous prairie and pine voles, and promiscuous meadow and montane voles, using in situ hybridization of CRF and Ucn1 mRNA. Our results reveal that CRF mRNA expression patterns in all four vole species appear highly conserved throughout the brain, including the olfactory bulb, nucleus accumbens, bed nucleus of the stria terminalis, medial preoptic area, central amygdala, hippocampus, posterior thalamus, and cerebellum. Similarly, Ucn1 mRNA primarily localized to the Edinger-Westphal nucleus in all four vole species. Immunocytochemistry in prairie and meadow voles confirmed localization of CRF and Ucn1 protein to these previously identified brain regions. These data demonstrate a striking dichotomy between the extraordinary species diversity of brain receptor patterns when compared to the highly conserved brain distributions of their respective ligands. Our findings generate novel hypotheses regarding the evolutionary mechanisms underlying the neural circuitry of species-typical social behaviors.
doi:10.1159/000094360
PMCID: PMC1828133  PMID: 16816534
Corticotropin-releasing hormone; CRF1; CRF2; median raphe; nucleus accumbens; Edinger-Westphal nucleus; CRF Corticotropin-releasing factor; Ucn1 Urocortin 1; OB olfactory bulb; NAcc nucleus accumbens; BnST bed nucleus of stria terminalis; MPOA medial preoptic area; PVN paraventricular nucleus of the hypothalamus; hippo hippocampus; CeA central nucleus of the amygdala; thal posterior thalamus; MR median raphe nucleus; CBg cerebellum granular layer; EW Edinger-Westphal nucleus
18.  Keeping Sensory Cells and Evolving Neurons to Connect Them to the Brain: Molecular Conservation and Novelties in Vertebrate Ear Development 
Brain, behavior and evolution  2004;64(3):182-197.
The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an ‘organ’ system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.
doi:10.1159/000079746
PMCID: PMC1242196  PMID: 15353909
Ear evolution; Hair cell; Mechanosensory neurons; Molecular evolution; Mechanosensory channels
19.  Two Visual Processing Pathways Are Targeted by Gonadotropin-Releasing Hormone in the Retina 
In fish the terminal nerve is comprised of a group of cells with somata adjacent to the olfactory bulb and processes that extend both anteriorly to the olfactory mucosa and posteriorly to the telencephalon. In teleost fish an additional group of axons extends along the optic tract and delivers putative neuromodulators to the retina. One peptide – gonadotropin-releasing hormone (GnRH) – has been implicated as a prime candidate neuromodulator based on electrophysiological evidence that exogenous application influences neural activity. Here we describe the expression patterns of two GnRH receptor subtypes in the retina of a teleost fish, Astatotilapia (Haplochromis) burtoni. The type 1 GnRH receptor (GnRH-R1) was expressed in cells of the amacrine cell layer – where lateral inputs affect the flow of visual information from photoreceptors to the brain – and in a distribution and location pattern similar to dopaminergic interplexiform cells. Immunohistochemical labeling of GnRH fibers revealed varicosities along terminal nerve axons near the amacrine cell layer and near cells immunoreactive for tyrosine hydroxylase, a dopaminergic cell marker. This finding supports an existing model that the terminal nerve forms synapses with dopaminergic interplexiform cells. Surprisingly, the type 2 GnRH receptor (GnRH-R2) was abundantly expressed in ganglion cells, which lie along the direct pathway of visual information to the brain. These data suggest that GnRH from the TN could broadly influence processing of retinal signals both in lateral processing circuits through GnRH-R1 and in the vertical throughput pathway through GnRH-R2.
doi:10.1159/000085043
PMCID: PMC1167600  PMID: 15821344
Terminal nerve; Teleost; Amacrine cell; Retinal ganglion cell; GNRH; Receptor; Fish
20.  Sylvian Fissure Asymmetries in Nonhuman Primates Revisited: A Comparative MRI Study 
Brain, behavior and evolution  2000;56(6):293-299.
Magnetic resonance images (MRI) were collected in a sample of 28 apes, 16 Old World monkeys and 8 New World monkeys. The length of the sylvian fissure (SF) and the superior temporal sulcus (STS) was traced in each hemisphere from three regions of the cerebral cortex. These three regions were labeled according to their position on the sagittal plane as lateral, medial and insular. It was hypothesized that the length and asymmetry of these fissures would be dependent on the region of measurement and that a leftward asymmetry in the SF and STS would be more robust in the great ape sample than for the monkeys. The results indicated within the ape sample a population-level leftward asymmetry in the medial and insular regions of the SF. Within the Old and New World monkey samples, the SF was leftward in the medial region at the population level, but not at the insular region. Additionally, the Old World monkeys exhibited a population-level rightward lateral SF and a rightward lateral STS. No other families exhibited population-level asymmetries in the lateral region of the SF or in any region of the STS. These results are consistent with findings reported in apes and, to a lesser extent, monkeys. MRI has excellent potential for comparing neuroanatomy across taxonomic families that will help future investigations.
PMCID: PMC2018745  PMID: 11326134
Sylvian fissure; Magnetic resonance imaging; Non-human primates; Asymmetry

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