Two C++ libraries for counting trees on a phylogenetic terrace.

Motivation: The presence of terraces in phylogenetic tree space, i.e. a potentially large number of distinct tree topologies that have exactly the same analytical likelihood score, was first described by Sanderson et al. However, popular software tools for maximum likelihood and Bayesian phylogenetic inference do not yet routinely report, if inferred phylogenies reside on a terrace, or not. We believe, this is due to the lack of an efficient library to (i) determine if a tree resides on a terrace, (ii) calculate how many trees reside on a terrace and (iii) enumerate all trees on a terrace. Results: In our bioinformatics practical that is set up as a programming contest we developed two efficient and independent C++ implementations of the SUPERB algorithm by Constantinescu and Sankoff (1995) for counting and enumerating trees on a terrace. Both implementations yield exactly the same results, are more than one order of magnitude faster, and require one order of magnitude less memory than a previous thirrd party python implementation. Availability and implementation: The source codes are available under GNU GPL at https://github.com/terraphast. Supplementary information: Supplementary data are available at Bioinformatics online.

Multi-rate Poisson tree processes for single-locus species delimitation under maximum likelihood and Markov chain Monte Carlo.

MOTIVATION: In recent years, molecular species delimitation has become a routine approach for quantifying and classifying biodiversity. Barcoding methods are of particular importance in large-scale surveys as they promote fast species discovery and biodiversity estimates. Among those, distance-based methods are the most common choice as they scale well with large datasets; however, they are sensitive to similarity threshold parameters and they ignore evolutionary relationships. The recently introduced "Poisson Tree Processes" (PTP) method is a phylogeny-aware approach that does not rely on such thresholds. Yet, two weaknesses of PTP impact its accuracy and practicality when applied to large datasets; it does not account for divergent intraspecific variation and is slow for a large number of sequences. RESULTS: We introduce the multi-rate PTP (mPTP), an improved method that alleviates the theoretical and technical shortcomings of PTP. It incorporates different levels of intraspecific genetic diversity deriving from differences in either the evolutionary history or sampling of each species. Results on empirical data suggest that mPTP is superior to PTP and popular distance-based methods as it, consistently yields more accurate delimitations with respect to the taxonomy (i.e., identifies more taxonomic species, infers species numbers closer to the taxonomy). Moreover, mPTP does not require any similarity threshold as input. The novel dynamic programming algorithm attains a speedup of at least five orders of magnitude compared to PTP, allowing it to delimit species in large (meta-) barcoding data. In addition, Markov Chain Monte Carlo sampling provides a comprehensive evaluation of the inferred delimitation in just a few seconds for millions of steps, independently of tree size. AVAILABILITY AND IMPLEMENTATION: mPTP is implemented in C and is available for download at http://github.com/Pas-Kapli/mptp under the GNU Affero 3 license. A web-service is available at http://mptp.h-its.org . CONTACT: : paschalia.kapli@h-its.org or alexandros.stamatakis@h-its.org or tomas.flouri@h-its.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Efficient Detection of Repeating Sites to Accelerate Phylogenetic Likelihood Calculations.

The phylogenetic likelihood function (PLF) is the major computational bottleneck in several applications of evolutionary biology such as phylogenetic inference, species delimitation, model selection, and divergence times estimation. Given the alignment, a tree and the evolutionary model parameters, the likelihood function computes the conditional likelihood vectors for every node of the tree. Vector entries for which all input data are identical result in redundant likelihood operations which, in turn, yield identical conditional values. Such operations can be omitted for improving run-time and, using appropriate data structures, reducing memory usage. We present a fast, novel method for identifying and omitting such redundant operations in phylogenetic likelihood calculations, and assess the performance improvement and memory savings attained by our method. Using empirical and simulated data sets, we show that a prototype implementation of our method yields up to 12-fold speedups and uses up to 78% less memory than one of the fastest and most highly tuned implementations of the PLF currently available. Our method is generic and can seamlessly be integrated into any phylogenetic likelihood implementation. [Algorithms; maximum likelihood; phylogenetic likelihood function; phylogenetics].

The phylogenetic likelihood library.

We introduce the Phylogenetic Likelihood Library (PLL), a highly optimized application programming interface for developing likelihood-based phylogenetic inference and postanalysis software. The PLL implements appropriate data structures and functions that allow users to quickly implement common, error-prone, and labor-intensive tasks, such as likelihood calculations, model parameter as well as branch length optimization, and tree space exploration. The highly optimized and parallelized implementation of the phylogenetic likelihood function and a thorough documentation provide a framework for rapid development of scalable parallel phylogenetic software. By example of two likelihood-based phylogenetic codes we show that the PLL improves the sequential performance of current software by a factor of 2-10 while requiring only 1 month of programming time for integration. We show that, when numerical scaling for preventing floating point underflow is enabled, the double precision likelihood calculations in the PLL are up to 1.9 times faster than those in BEAGLE. On an empirical DNA dataset with 2000 taxa the AVX version of PLL is 4 times faster than BEAGLE (scaling enabled and required). The PLL is available at http://www.libpll.org under the GNU General Public License (GPL).

OmegaPlus: a scalable tool for rapid detection of selective sweeps in whole-genome datasets.

UNLABELLED: Recent advances in sequencing technologies have led to the rapid accumulation of molecular sequence data. Analyzing whole-genome data (as obtained from next-generation sequencers) from intra-species samples allows to detect signatures of positive selection along the genome and therefore identify potentially advantageous genes in the course of the evolution of a population. We introduce OmegaPlus, an open-source tool for rapid detection of selective sweeps in whole-genome data based on linkage disequilibrium. The tool is up to two orders of magnitude faster than existing programs for this purpose and also exhibits up to two orders of magnitude smaller memory requirements. AVAILABILITY: OmegaPlus is available under GNU GPL at http://www.exelixis-lab.org/software.html.

RAxML-Light: a tool for computing terabyte phylogenies.

MOTIVATION: Due to advances in molecular sequencing and the increasingly rapid collection of molecular data, the field of phyloinformatics is transforming into a computational science. Therefore, new tools are required that can be deployed in supercomputing environments and that scale to hundreds or thousands of cores. RESULTS: We describe RAxML-Light, a tool for large-scale phylogenetic inference on supercomputers under maximum likelihood. It implements a light-weight checkpointing mechanism, deploys 128-bit (SSE3) and 256-bit (AVX) vector intrinsics, offers two orthogonal memory saving techniques and provides a fine-grain production-level message passing interface parallelization of the likelihood function. To demonstrate scalability and robustness of the code, we inferred a phylogeny on a simulated DNA alignment (1481 taxa, 20 000 000 bp) using 672 cores. This dataset requires one terabyte of RAM to compute the likelihood score on a single tree. CODE AVAILABILITY: https://github.com/stamatak/RAxML-Light-1.0.5 DATA AVAILABILITY: http://www.exelixis-lab.org/onLineMaterial.tar.bz2 CONTACT: alexandros.stamatakis@h-its.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of neonatal handling on adult rat spatial learning and memory following acute stress.

Brief neonatal handling permanently alters hypothalamic-pituitary-adrenal axis function resulting in increased ability to cope with stress. Since stress is known to affect cognitive abilities, in the present study we investigated the effect of brief (15 min) handling on learning and memory in the Morris water maze, following exposure to an acute restraint stress either before training or recall. Exposure of non-handled rats to the acute stress prior to training resulted in quicker learning of the task, than in the absence of the stressor. When acute stress preceded acquisition, male handled rats showed an overall better learning performance, and both sexes of handled animals were less impaired in the subsequent memory trial, compared to the respective non-handled. In addition, the number of neurons immunoreactive for GR was higher in all areas of Ammon's horn of the handled rats during the recall. In contrast, the number of neurons immunoreactive for MR was higher in the CA1 and CA2 areas of the non-handled males. When the acute restraint stress was applied prior to the memory test, neonatal handling was not effective in preventing mnemonic impairment, as all animal groups showed a similar deficit in recall. In this case, no difference between handled and non-handled rats was observed in the number of GR positive neurons in the CA2 and CA3 hippocampal areas during the memory test. These results indicate that early experience interacts with sex and acute stress exposure in adulthood to affect performance in the water maze. Hippocampal corticosterone receptors may play a role in determining the final outcome.

Cellular mechanisms underlying the effect of a single exposure to neonatal handling on neurotrophin-3 in the brain of 1-day-old rats.

Neurotrophin-3 (NT-3) has an important role in brain development and is thus a good candidate molecule to be involved in the cellular mechanisms mediating the effects of early experiences on the brain. In the present work we employed the model of neonatal handling, which is known to affect the ability of the adult organism to respond to stressful stimuli, and determined its effects on NT-3 levels in the rat hippocampus and cortex 2, 4 and 8 h after handling on postnatal day 1. We also recorded maternal behavior during the 8 h following handling. At both the 4 and 8 h time-points there was an increase in NT-3 positive cells in field 1 of Ammon's horn (CA1 area of the hippocampus) and parietal cortex of the handled animals. In the parietal cortex NT-3 levels increased with time following handling: at 8 h there were more NT-3 positive cells than at 4 h. During the 4 h following the end of handling, handled pups were subject to more maternal licking, indicating that the more intense maternal care could underlie the handling-induced increase in NT-3. In the hippocampus, the handling induced increase in NT-3 was cancelled by inhibition of N-methyl-D-aspartate (NMDA), AMPA/kainate, or GABA-A receptors, as well as L-type voltage-gated Ca(2+) channels. It thus appears that neonatal handling activates these neurotransmitter receptors and channels, leading to increased intracellular Ca(2+) and increased NT-3 expression. NT-3 can then activate downstream effectors and exert its morphogenetic actions and thus imprint the effects of handling on the brain.

Effects of neonatal handling on the basal forebrain cholinergic system of adult male and female rats.

Neonatal handling is an early experience which results in improved function of the hypothalamic-pituitary-adrenal axis, increased adaptability and coping as a response to stress, as well as better cognitive abilities. In the present study, we investigated the effect of neonatal handling on the basal forebrain cholinergic system, since this system is known to play an important role in cognitive processes. We report that neonatal handling results in increased number of choline-acetyl transferase immunopositive cells in the septum/diagonal band, in both sexes, while no such effect was observed in the other cholinergic nuclei, such as the magnocellular preoptic nucleus and the nucleus basalis of Meynert. In addition, neonatal handling resulted in increased M1 and M2 muscarinic receptor binding sites in the cingulate and piriform cortex of both male and female rats. A handling-induced increase in M1 muscarinic receptor binding sites was also observed in the CA3 and CA4 (fields 3 and 4 of Ammon's horn) areas of the hippocampus. Furthermore, a handling-induced increase in acetylcholinesterase staining was found only in the hippocampus of females. Our results thus show that neonatal handling acts in a sexually dimorphic manner on one of the cholinergic parameters, and has a beneficial effect on BFCS function, which could be related to the more efficient and adaptive stress response and the superior cognitive abilities of handled animals.

Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function.

It has been reported recently that mice lacking both alleles of the LIM-homeobox gene Lhx7, display dramatically reduced number of forebrain cholinergic neurons. In the present study, we investigated whether the Lhx7 mutation affects male and female mice differently, given the fact that gender differences are consistently observed in forebrain cholinergic function. Our results show that in adult male as well as female Lhx7 homozygous mutants there is a dramatic loss of choline acetyltransferase immunoreactive forebrain neurons, both projection and interneurons. The reduction of forebrain choline acetyltransferase immunoreactive neurons in Lhx7 homozygous mutants is accompanied by a decrease of acetylcholinesterase histochemical staining in all forebrain cholinergic neuron target areas of both male and female homozygous mutants. Furthermore, there was an increase of M1-, but not M2-, muscarinic acetylcholine receptor binding site density in the somatosensory cortex and basal ganglia of only the female homozygous mutant mice. Such an increase can be regarded as a mechanism acting to compensate for the dramatically reduced cholinergic input, raising the possibility that the forebrain cholinergic system in female mice may be more plastic and responsive to situations of limited neurotransmitter availability. Finally, our study provides additional data for the sexual dimorphism of the forebrain cholinergic system, as female mice appear to have a lower density of M1-muscarinic acetylcholine receptors in the striatal areas of the basal ganglia and a higher density of M2-muscarinic acetylcholine receptors, in a number of cortical areas, as well as the striatal areas of the basal ganglia.

Effect of neonatal handling on serotonin 1A sub-type receptors in the rat hippocampus.

Serotonin 1A sub-type receptors play an important role in the etiopathogenesis of depression, which is known to occur more often in females than males. Early experiences can be a predisposing factor for depression; however, the underlying cellular processes remain unknown. In an effort to address such issues, we employed neonatal handling, an experimental model of early experience, which has been previously shown to render females more vulnerable to display enhanced depression-like behavior in response to chronic stress, while it increases the ability of males to cope. In rat pre-pubertal (30 days of age) and adult (90 days) hippocampus, of both males and females, the effect of neonatal handling on serotonin 1A sub-type receptor mRNA and protein levels was determined by in situ hybridization and immunohistochemistry, respectively, while the number of binding sites was determined by in vitro autoradiography using [(3)H]8-hydroxy-2(di-n-propylamino)tetralin as the ligand. Our results revealed a significant sex difference in serotonin 1A sub-type receptor mRNA, protein and binding sites, with females having higher levels than males. Handling resulted in statistically significant decreased numbers of cells positive for serotonin 1A sub-type receptor mRNA or protein, as well as [(3)H]8-hydroxy-2(di-n-propylamino)tetralin binding sites in the area 4 of Ammon's horn and dentate gyrus of both pre-pubertal males and females. In adult animals the number of serotonin 1A sub-type receptor mRNA positive cells was increased as a result of handling in the area 1 of Ammon's horn, area 4 of Ammon's horn and dentate gyrus of males, while it was decreased only in the area 4 of Ammon's horn of females. Furthermore, the number of serotonin sub-type 1A receptor immunopositive cells, as well as [(3)H]8-hydroxy-2(di-n-propylamino)tetralin binding sites was increased in the area 1 of Ammon's horn, area 4 of Ammon's horn and dentate gyrus of handled males, whereas it was decreased in these same brain areas in the handled females. We can thus infer that neonatal handling results in alterations in postsynaptic serotonergic neurotransmission, which may contribute to the sex dimorphic effects of handling as to the vulnerability toward depression-like behavior in response to chronic stressful stimuli.

The levels of the GluN2A NMDA receptor subunit are modified in both the neonatal and adult rat brain by an early experience involving denial of maternal contact.

The composition of the N-methyl-d-aspartate receptor receptor in GluN2A/GluN2B subunits is important in determining its characteristics and its role in plasticity, a property of the brain which is known to be critically affected by early experiences. In the present work we employed an early experience model involving either receipt (RER) or denial (DER) of the expected reward of maternal contact within the context of learning by the pups of a T-maze on postnatal days (PND) 10-13. We investigated the effects of the RER and DER early experiences on GluN1, GluN2A and GluN2B levels in the prefrontal cortex (PFC), hippocampus and amygdala of the rat. We show that on PND13 the DER animals had lower GluN2A levels in the PFC. In adulthood DER males had higher GluN2A levels in the hippocampus, both under basal conditions and after exposure to a novel environment. The early experiences did not affect the response to the novelty. After exposure to a novel environment animals of all three groups (DER, RER, Control) responded with an increase in GluN2A levels in the brain areas examined. We did not detect any effects on GluN1 or GluN2B levels. The alterations in GluN2A levels observed in the DER animals could in part be responsible for their behavioral phenotype, described previously, which includes an increased susceptibility for the expression of depressive-like behavior.

Effects of pre- and postnatal exposure to 1880-1900MHz DECT base radiation on development in the rat.

In the present study, to evaluate the effects of wireless 1880-1900MHz Digital Enhanced Communication Telephony (DECT) base radiation on fetal and postnatal development, Wistar rats were exposed at an average electric field intensity of 3.7V/m, 12h/day, during pregnancy. After parturition, a group of dams and offspring were similarly exposed for another 22days. Controls were sham-exposed. The data showed that DECT base radiation exposure caused heart rate increase in the embryos on the 17th day of pregnancy. Moreover, significant changes on the newborns' somatometric characteristics were noticed. Pyramidal cell loss and glia fibrilliary acidic protein (GFAP) over-expression were detected in the CA4 region of the hippocampus of the 22-day old pups that were irradiated either during prenatal life or both pre- and postnatally. Changes in the integrity of the brain in the 22-day old pups could potentially be related to developmental behavioral changes during the fetal period.

INSECT PHYLOGENOMICS. Response to Comment on "Phylogenomics resolves the timing and pattern of insect evolution".

Tong et al. comment on the accuracy of the dating analysis presented in our work on the phylogeny of insects and provide a reanalysis of our data. They replace log-normal priors with uniform priors and add a "roachoid" fossil as a calibration point. Although the reanalysis provides an interesting alternative viewpoint, we maintain that our choices were appropriate.

Differential effects of testosterone on protein synthesis activity in male and female quail brain.

In Japanese quail, testosterone (T) increases the Nissl staining density in the medial preoptic nucleus (POM) in relation to the differential activation by T of copulatory behavior. The effect of T on protein synthesis was quantified here in 97 discrete brain regions by the in vivo autoradiographic (14)C-leucine (Leu) incorporation method in adult gonadectomized male and female quail that had been treated for 4 weeks with T or left without hormone. T activated male sexual behaviors in males but not females. Overall Leu incorporation was increased by T in five brain regions, many of which contain sex steroid receptors such as the POM, archistriatum and lateral hypothalamus. T decreased Leu incorporation in the medial septum. Leu incorporation was higher in males than females in two nuclei but higher in females in three nuclei including the hypothalamic ventromedial nucleus. Significant interactions between effects of T and sex were seen in 13 nuclei: in most nuclei (n=12), T increased Leu incorporation in males but decreased it in females. The POM boundaries were defined by a denser Leu incorporation than the surrounding area and incorporation was increased by T more in males (25%) than in females (6%). These results confirm that protein synthesis in brain areas relevant to the control of sexual behavior can be affected by the sex of the subjects or their endocrine condition and that T can have differential effects in the two sexes. These anabolic changes should reflect the sexually differentiated neurochemical mechanisms mediating behavioral activation.

Effects of lesions of the medial preoptic nucleus on the testosterone-induced metabolic changes in specific brain areas in male quail.

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.

Performance of appetitive or consummatory components of male sexual behavior is mediated by different brain areas: a 2-deoxyglucose autoradiographic study.

The in vivo autoradiographic deoxyglucose method was used to identify the functional brain circuits that are involved in the performance of appetitive and consummatory components of male sexual behavior in Japanese quail (Coturnix japonica). Two groups of castrated, testosterone-treated male quail were trained during 12 sessions to associate the view of a female behind a window with the opportunity to interact freely and to copulate with her. They developed, as a consequence, a social proximity response (staying close and looking through the window providing a view of the female) that has been used in previous experiments to measure appetitive sexual behavior. A third control group (also castrated and treated with testosterone) was allowed to view the female but not to copulate with her and therefore did not develop this proximity response. 2-14C-deoxyglucose was then injected i.p. to these birds and they were allowed to either copulate freely with a female (consummatory sexual behavior group) or express the social proximity response (appetitive sexual behavior group). The control group was provided a view of the female but these birds, although they were exposed to the same stimuli as birds in the appetitive group, did not express the social proximity response because they had never learned the association with the opportunity to copulate. Birds were killed 45 min after the deoxyglucose injection and their brains were processed for autoradiography. Densitometric analyses of the autoradiograms revealed that the expression of appetitive or consummatory aspects of male sexual behavior was associated with significant increases by comparison with the control group in the deoxyglucose incorporation in the nucleus mesencephalicus lateralis, pars dorsalis and in the nucleus leminsci lateralis. In addition, an increase in the deoxyglucose incorporation was specifically observed in the paleostriatum primitivum, rostral preoptic area, nucleus intercollicularis, nucleus interpeduncularis and third nerve but a decrease was observed in the dorsomedial part of the hippocampus and in the nucleus nervi oculomotori in birds of the consummatory sexual behavior group by comparison with controls. By contrast, in the appetitive sexual behavior group, significant increases in deoxyglucose incorporation were observed in two telencephalic areas, the intermediate hyperstriatum ventrale and neostriatum caudolaterale by comparison with the controls, but decreases were detected in the stratum griseum et fibrosum superficiale of optic tectum by comparison with the consummatory behavior group. These studies demonstrate that the performance of appetitive or consummatory components of male sexual behavior affects in a specific manner the deoxyglucose uptake and accumulation in specific regions of the quail brain. Changes in metabolic activity were observed in steroid-sensitive areas, in auditory, visual and vocal brain regions, and in brain nuclei related to motor behavior but also in association telencephalic and limbic structures. These changes in oxidative metabolism overlap to some extent with metabolic changes as revealed by immunocytochemistry for the immediate early gene products Fos and Zenk, but many specific reactions are also detected indicating that these techniques are not necessarily redundant and, together, they can provide a more complete picture of the brain circuits that are implicated in the control and performance of complex behaviors.

Laminar pattern of NADPH-diaphorase activity in the developing avian cerebellum.

The present study aimed to define the distribution of NADPH-diaphorase (NADPH-d) positive cells and fibers in the developing chick cerebellum. From embryonic day 9 (E9) until day E15 NADPH-d positive ascending axons, originating from pontine nuclei, targeted selectively the developing folia. Cerebellar cortex exhibited weak NADPH-d activity until day E15, when NADPH-d negative granule cells of external granular layer began inward migration. From that embryonic age, differentiated granule, Golgi II type cells and glomeruli of the internal granular layer exhibited gradually increasing diaphorase activity. In the molecular layer diffuse activity increased, possibly due to the development of the parallel fibers. Transient NADPH-d activity appeared on Purkinje somata (PC) at day E17 and by posthatching day 1 all PC were devoid of diaphorase activity. Our data support the hypothesis that neurons producing nitric oxide (NO) are involved in the activity dependent developmental processes for the establishment of connections and normal cytoarchitecture.

Passive avoidance learning involves alpha2-noradrenergic receptors in a day old chick.

Day-old chicks were trained on one-trial passive avoidance task, using methyl-anthranilate (MeA) as an aversive substance. Bilateral pharmacological manipulation of the intermediate hyperstriatum ventrale was performed by intracerebral application of an alpha2-noradrenergic agonist, clonidine (5 microM), or an antagonist, rauwolscine (300 microM). Only rauwolscine application (pre- or post-training) induced significant memory impairment. Quantitative receptor autoradiography was used to determine the kinetic properties of the binding sites for [3H]clonidine or [3H]rauwolscine in MeA-trained or water-trained (control) chicks, in forebrain areas known to be involved in avoidance learning. Scatchard analysis revealed that MeA-training resulted in a significant bilateral upregulation in the number of [3H]rauwolscine binding sites (Bmax) in the area of hyperstriatum ventrale. These findings suggest the importance of activation of alpha2-noradrenergic receptors in aversive learning in chicks.

A quantitative autoradiographic comparison of binding to glutamate receptor sub-types in hippocampus and forebrain regions of a food-storing and a non-food-storing bird.

In two species of birds, food-storing marsh tits, P. palustris, and non-storing blue tits, P. caeruleus, quantitative receptor autoradiography was used to localize NMDA (N-methyl-D-aspartate)-sensitive [3H]glutamate, [3H]MK801, and [3H]AMPA binding sites, in six regions of the forebrain: hippocampus and parahippocampus, hyperstriatum accessorium (vision) and ventrale (sensory integration), neostriatum (auditory), and lobus parolfactorius (basal ganglia). In both species high levels of labelling to both NMDA and AMPA receptors were observed throughout the forebrain. However, a marked difference in receptor labelling was apparent between the two species, with levels of binding to NMDA ion channel sites being significantly lower (20%) in both the hippocampus and parahippocampus, in food storers compared to non-food storers. The levels of binding to other forebrain regions were remarkably similar in the two species. No differences were seen in the binding to AMPA receptors in forebrain regions of either species.