Calcitonin gene related peptide α is dispensable for many danger-related motivational responses.

Calcitonin gene related peptide (CGRP) expressing neurons in the parabrachial nucleus have been shown to encode danger. Through projections to the amygdala and other forebrain structures, they regulate food intake and trigger adaptive behaviors in response to threats like inflammation, intoxication, tumors and pain. Despite the fact that this danger-encoding neuronal population has been defined based on its CGRP expression, it is not clear if CGRP is critical for its function.

Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons.

Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a negative affective state characterized by anhedonia and aversion, whereas inactivation of microglia blocked aversion induced by systemic inflammation.

Motivational valence is determined by striatal melanocortin 4 receptors.

It is critical for survival to assign positive or negative valence to salient stimuli in a correct manner. Accordingly, harmful stimuli and internal states characterized by perturbed homeostasis are accompanied by discomfort, unease, and aversion. Aversive signaling causes extensive suffering during chronic diseases, including inflammatory conditions, cancer, and depression.

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test.

Interferon-ɣ mediated signaling in the brain endothelium is critical for inflammation-induced aversion.

Systemic inflammation elicits malaise and a negative affective state. The mechanism underpinning the aversive component of inflammation include cerebral prostaglandin synthesis and modulation of dopaminergic reward circuits, but the messengers that mediate the signaling between the peripheral inflammation and the brain have not been sufficiently characterized. Here we investigated the role of interferon-ɣ (IFN-ɣ) in the aversive response to systemic inflammation induced by a low dose (10μg/kg) of lipopolysaccharide (LPS) in mice.

Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain.

Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus.

Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.

Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia.

Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice.

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort.

Land-bridge calibration of molecular clocks and the post-glacial Colonization of Scandinavia by the Eurasian field vole Microtus agrestis.

Phylogeography interprets molecular genetic variation in a spatial and temporal context. Molecular clocks are frequently used to calibrate phylogeographic analyses, however there is mounting evidence that molecular rates decay over the relevant timescales. It is therefore essential that an appropriate rate is determined, consistent with the temporal scale of the specific analysis.

Cryptic speciation in the field vole: a multilocus approach confirms three highly divergent lineages in Eurasia.

Species are generally described from morphological features, but there is growing recognition of sister forms that show substantial genetic differentiation without obvious morphological variation and may therefore be considered 'cryptic species'. Here, we investigate the field vole (Microtus agrestis), a Eurasian mammal with little apparent morphological differentiation but which, on the basis of previous sex-linked nuclear and mitochondrial DNA (mtDNA) analyses, is subdivided into a Northern and a Southern lineage, sufficiently divergent that they may represent two cryptic species. These earlier studies also provided limited evidence for two major mtDNA lineages within Iberia.

Asymmetric and differential gene introgression at a contact zone between two highly divergent lineages of field voles (Microtus agrestis).

Secondary contact zones have the potential to shed light on the mode and rate at which reproductive isolation accumulates during allopatric speciation. We investigated the population genetics of a contact zone between two highly divergent lineages of field voles (Microtus agrestis) in the Swiss Jura mountains. To shed light on the processes underlying introgression, we used maternally, paternally, and bi-parentally inherited markers.

Origin and timing of the horizontal transfer of a PgiC gene from Poa to Festuca ovina.

A segregating second locus, PgiC2, for the enzyme phosphoglucose isomerase (PGIC) is found in the grass sheep's fescue, Festuca ovina. We have earlier reported that a phylogenetic analysis indicates that PgiC2 has been horizontally transferred from the reproductively separated grass genus Poa. Here we extend our analysis to include intron and exon information on 27 PgiC sequences from 18 species representing five genera, and confirm our earlier finding.

Multigenic and morphometric differentiation of ground squirrels (Spermophilus, Scuiridae, Rodentia) in Turkey, with a description of a new species.

This study reports on the molecular phylogenetics of ground squirrels, genus Spermophilus, in Turkey using cytochrome b (1140bp), part of the D-loop and flanking tRNAs (572bp), X chromosome (867-1051bp) and Y chromosome (983-989bp) DNA sequences. Individuals also were characterized by karyotype and with geometric morphometric analyses of mandibles and skulls. Two hundred fourteen individuals from 91 localities were studied.

The introgression of a functional nuclear gene from Poa to Festuca ovina.

In sheep's fescue, Festuca ovina, genes coding for the cytosolic enzyme phosphoglucose isomerase, PGIC, are not only found at the standard locus, PgiC1, but also at a segregating second locus, PgiC2. We have used PCR-based sequencing to characterize the molecular structure and evolution of five PgiC1 and three PgiC2 alleles in F. ovina.

Analysis of sex-linked sequences supports a new mammal species in Europe.

European mammals have been the focus of particularly detailed taxonomic studies by traditional morphological methods. However, DNA analyses have the potential to reveal additional, cryptic species. We describe two highly divergent evolutionary lineages within a small Eurasian mammal, the field vole (Microtus agrestis).

Molecular phylogeny of the speciose vole genus Microtus (Arvicolinae, Rodentia) inferred from mitochondrial DNA sequences.

Voles of the genus Microtus represent one of the most speciose mammalian genera in the Holarctic. We established a molecular phylogeny for Microtus to resolve contentious issues of systematic relationships and evolutionary history in this genus. A total of 81 specimens representing ten Microtus species endemic to Europe as well as eight Eurasian, six Asian and one Holarctic species were sequenced for the entire cytochrome b gene (1140 bp).

A highly divergent mitochondrial DNA lineage of Microtus agrestis in southern Europe.

The Mediterranean peninsulas constitute important areas for endemism and intraspecific variation, and are likely places for cryptic biodiversity. We assessed the phylogeographic pattern of field voles (Microtus agrestis) in southern and central Europe by sequence analysis of a 385-bp fragment of the mitochondrial cytochrome b gene in 74 specimens from 44 localities. The majority of samples consisted of skulls collected from owl pellets.

Holarctic phylogeography of the root vole (Microtus oeconomus): implications for late Quaternary biogeography of high latitudes.

A species-wide phylogeographical study of the root vole (Microtus oeconomus) was performed using the whole 1140 base pair mitochondrial (mt) cytochrome b gene. We examined 83 specimens from 52 localities resulting in 65 unique haplotypes. Our results demonstrate that the root vole is divided into four main mtDNA phylogenetic lineages that seem to have largely allopatric distributions.

Phylogeography of the common vole (Microtus arvalis) with particular emphasis on the colonization of the Orkney archipelago.

To investigate the human introduction of the common vole Microtus arvalis onto the Orkney islands, the complete cytochrome b gene was sequenced in 41 specimens from both Orkney (four localities) and elsewhere in their range (26 localities). Orkney voles belonged to the same phylogenetic lineage, 'Western', as individuals from France and Spain indicating southwestern Europe as the most likely source area for the islands. This result is of interest with respect to the movement and trading links of the Neolithic people who likely transported the voles.

Phylogeography of lemmings (Lemmus): no evidence for postglacial colonization of Arctic from the Beringian refugium.

Beringia is considered as an important glacial refugium that served as the main source for colonization of formerly glaciated Arctic regions. To obtain high resolution views of Arctic refugial history, we examined mitochondrial cytochrome b phylogeography in the northern genus of rodents, Lemmus (true lemmings), sampled across its circumpolar distribution. Strong phylogeographical structure suggests vicariant separation over several glacial-interglacial periods and does not provide evidence supporting the importance of Beringia for extensive colonization of formerly glaciated regions.

Phylogeography of field voles (Microtus agrestis) in Eurasia inferred from mitochondrial DNA sequences.

In a distribution-wide phylogeographic survey of the field vole (Microtus agrestis), 75 specimens from 56 localities across Eurasia were examined for DNA sequence variation along the whole 1140 base pair (bp) mitochondrial (mt) cytochrome b gene. The species is subdivided into three main mtDNA phylogeographic groups - western, eastern and southern - with largely allopatric distributions. The western phylogeographical group is found in west and central Europe and spread most probably from a glacial refugium in the Carpathians.

Direct evidence for suppression of recombination within two pericentric inversions in humans: a new sperm-FISH technique.

Crossover within a pericentric inversion produces reciprocal recombinant chromosomes that are duplicated/deficient for all chromatin distal to the breakpoints. In view of this fact, a new technique is presented for estimating the frequency of recombination within pericentric inversions. YAC probes were selected from within the q- and p-arm flanking regions of two human inversions, and two-color FISH analysis was performed on sperm from heterozygous inversion carriers.

The mouse H19 locus mediates a transition between imprinted and non-imprinted DNA replication patterns.

Genes subject to genomic imprinting generally occur in clusters of hundreds of kilobases. These domains exhibit several gamete of origin-dependent manifestations, including a pattern of asynchronous replication when studied by fluorescence in situ hybridization (FISH). We find a transition from asynchronous replication at the imprinted mouse H19 gene to synchronous replication at the downstream Rpl23 gene, the human homologue of which appears to be non-imprinted.

The occurrence of mountain hare mitochondrial DNA in wild brown hares.

If interspecific hybrids are fertile and backcross to either parental species, transmission of mitochondrial DNA over the species barrier can occur. To investigate if such transmission has occurred between the brown hare Lepus europeus Pall and the mountain hare L. timidus L.

A CONTACT ZONE WITH NONCOINCIDENT CLINES FOR SEX-SPECIFIC MARKERS IN THE FIELD VOLE (MICROTUS AGRESTIS).

A field vole (Microtus agrestis) population characterized by unique mitochondrial DNA (mtDNA) and Y chromosome markers occurs in southwest Sweden. A contact zone between this Lund (Lu) population and a standard (St) population was examined with two sex-specific genetic markers. The field vole mtDNA and Y chromosome clines display a remarkable lack of coincidence, rarely observed in contact zones.