Imaging of functional connectivity in the mouse brain

Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS). We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact) making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models.     

The brain activity map project and the challenge of functional connectomics

The function of neural circuits is an emergent property that arises from the coordinated activity of large numbers of neurons. To capture this, we propose launching a large-scale, international public effort, the Brain Activity Map Project, aimed at reconstructing the full record of neural activity across complete neural circuits. This technological challenge could prove to be an invaluable step toward understanding fundamental and pathological brain processes.     

Decreasing functional responses as a result of adaptive consumer behavior

Summary Several different mechanisms that may produce decreasing functional responses are investigated using models that assume that an optimally foraging consumer is exploiting one or two resources. Decreasing functional responses are associated with situations in which there are costs to resource consumption. If the process of resource acquisition has costs, decreasing functional responses may occur when there is a single homogeneous resource. If the cost is solely a function of the amount of resource ingested, decreasing functional responses on a single resource do not occur. Both types of cost can produce decreasing functional responses when there are two resource types and a trade-off relationship between consumption of one and consumption of the other. Decreasing functional responses seem to be most likely to occur on a food that yields high benefits and costs per unit of foraging time or effort when there is an alternative resource which yields low benefits and costs. Given this type of foraging choice, the functional response is most likely to decrease when the benefits of ingestion increase at a decreasing rate, and the costs of ingestion increase at an increasing rate with amount ingested. An important and unique consequence of decreasing functional responses is the possibility of population cycles in differential equation models of consumer-resource systems with non-reproducing resources; this is illustrated with a simple comsumer-resource model.     

Global functional map of the p23 molecular chaperone reveals an extensive cellular network

In parallel with evolutionary developments, the Hsp90 molecular chaperone system shifted from a simple prokaryotic factor into an expansive network that includes a variety of cochaperones. We have taken high-throughput genomic and proteomic approaches to better understand the abundant yeast p23 cochaperone Sba1. Our work revealed an unexpected p23 network that displayed considerable independence from known Hsp90 clients. Additionally, our data uncovered a broad nuclear role for p23, contrasting with the historical dogma of restricted cytosolic activities for molecular chaperones. Validation studies demonstrated that yeast p23 was required for proper Golgi function and ribosome biogenesis, and was necessary for efficient DNA repair from a wide range of mutagens. Notably, mammalian p23 had conserved roles in these pathways as well as being necessary for proper cell mobility. Taken together, our work demonstrates that the p23 chaperone serves a broad physiological network and functions both in conjunction with and sovereign to Hsp90.     

Imaging mitophagy in the fruit fly

Loss-of-function mutations in the genes encoding PRKN/parkin and PINK1 cause autosomal recessive Parkinson disease (PD). Seminal work in Drosophila revealed that loss of park/parkin and Pink1 causes prominent mitochondrial pathology in flight muscle and, to a lesser extent, in dopaminergic neurons. Subsequent studies in cultured mammalian cells discovered a crucial role for PRKN/PARK2 and PINK1 in selective macroautophagic removal of mitochondria (mitophagy). However, direct evidence for the existence of a PINK1-PRKN/PARK2-mediated mitophagy pathway in vivo is still scarce. Recently, we engineered Drosophila that express the mitophagy reporter mt-Keima. We demonstrated that mitophagy occurs in flight muscle cells and dopaminergic neurons in vivo and increases with aging. Moreover, this age-dependent rise depends on park and Pink1. Our data also suggested that some aspects of the mitochondrial phenotype of park- and Pink1-deficient flies are independent of the mitophagy defect, and that park and Pink1 may have multiple functions in the regulation of the integrity of these organelles. Here, we discuss implications of these findings as well as possible future applications of the mt-Keima fly model.     

A map of taste neuron projections in the Drosophila CNS

We provide a map of the projections of taste neurons in the CNS of Drosophila. Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr taste receptors, we systematically map the projections of neurons expressing these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion (SOG). We define 9 categories of projections in the thoracico-abdominal ganglia and 10 categories in the SOG. The projection patterns are modular, and can be interpreted as combinations of discrete pattern elements. The elements can be interpreted in terms of the taste organ from which the projections originate, the structures from which they originate, and the quality of taste information that they represent. The extensive diversity in projection patterns provides an anatomical basis for functional diversity in responses elicited by different taste stimuli.     

Novel odorant-binding proteins expressed in the taste tissue of the fly

A taste tissue cDNA library of the fleshfly Boettcherisca peregrina was screened with a subtracted cDNA probe enriched with taste-receptor-tissue-specific cDNA. Seven genes were identified with sequence similarity to insect odorant-binding protein (OBP) genes. The predicted amino acid sequences of the genes contain the putative signal peptide sequence at the N-terminal and most of them conserve the six cysteines common to known insect OBPs. These genes show a high degree of sequence divergence with approximately 20% amino acid identity. The most striking feature was that all seven of these genes are expressed mainly in the taste tissues, such as the labellum and tarsus, unlike the known insect OBP genes expressed in olfactory tissue. The predicted amino acid sequences had the highest degree of sequence similarity to the Drosophila melanogaster OBPs named pheromone binding protein-related proteins (PBPRPs). These gene products are here referred to as gustatory PBP-related proteins (GPBPRPs) 1-7. Homologous GPBPRP genes were found also in D. melanogaster by database search and are shown to be expressed in Drosophila taste tissues.     

Cortical network dynamics with time delays reveals functional connectivity in the resting brain

In absence of all goal-directed behavior, a characteristic network of cortical regions involving prefrontal and cingulate cortices consistently shows temporally coherent fluctuations. The origin of these fluctuations is unknown, but has been hypothesized to be of stochastic nature. In the present paper we test the hypothesis that time delays in the network dynamics play a crucial role in the generation of these fluctuations. By tuning the propagation velocity in a network based on primate connectivity, we scale the time delays and demonstrate the emergence of the resting state networks for biophysically realistic parameters.     

A confined taste area in a lepidopteran brain

Knowledge about the neuronal pathways of the taste system is interesting both for studying taste coding and appetitive learning of odours. We here present the morphology of the sensilla styloconica on the proboscis of the moth Heliothis virescens and the projections of the associated receptor neurones in the central nervous system. The morphology of the sensilla was studied by light microscopy and by scanning- and transmission electron microscopy. Each sensillum contains three or four sensory neurones; one mechanosensory and two or three chemosensory. The receptor neurones were stained with neurobiotin tracer combined with avidin-fluorescein conjugate, and the projections were viewed in a confocal laser-scanning microscope. The stained axons entered the suboesophageal ganglion via the maxillary nerves and were divided into two categories based on their projection pattern. Category one projected exclusively ipsilaterally in the dorsal suboesophageal ganglion/tritocerebrum and category two projected bilaterally and more ventrally in the suboesophageal ganglion confined to the anterior surface of the neuropil. The bilateral projecting neurones had one additional branch terminating ipsilaterally in the dorsal suboesophageal ganglion/tritocerebrum. A possible segregation of the two categories of projections as taste and mechanosensory is discussed.     

Linkage mapping reveals sex-dimorphic map distances in a passerine bird

Linkage maps are lacking for many highly influential model organisms in evolutionary research, including all passerine birds. Consequently, their full potential as research models is severely hampered. Here, we provide a partial linkage map and give novel estimates of sex-specific recombination rates in a passerine bird, the great reed warbler (Acrocephalus arundinaceus). Linkage analysis of genotypic data at 51 autosomal microsatellites and seven markers on the Z-chromosome (one of the sex chromosomes) from an extended pedigree resulted in 12 linkage groups with 2-8 loci. A striking feature of the map was the pronounced sex-dimorphism: males had a substantially lower recombination rate than females, which resulted in a suppressed autosomal map in males (sum of linkage groups: 110.2 cM) compared to females (237.2 cM; female/male map ratio: 2.15). The sex-specific recombination rates will facilitate the building of a denser linkage map and cast light on hypotheses about sex-specific recombination rates.     

Insect olfaction: a map of smell in the brain

Humans use three classes of photoreceptor to span the visible spectrum, but smell relies on hundreds of distinct classes of olfactory receptor neuron. Even the simple fruitfly has around 50 classes of olfactory receptor neuron. Two new studies map the projections of the great majority of these neurons into stereotyped positions in the fly brain, giving us an almost complete atlas of olfactory information transfer.