The Head-fixed Behaving Rat—Procedures and Pitfalls

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models—the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging

Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues

Although whisker-related perception is based predominantly on local, near-instantaneous coding, global, intensive coding, which integrates the vibrotactile signal over time, has also been shown to play a role given appropriate behavioral conditions. Here, we study global coding in isolation by studying head-fixed rats that identified pulsatile stimuli differing in pulse frequency but not in pulse waveforms, thus abolishing perception based on local coding. We quantified time locking and spike counts as likely variables underpinning the 2 coding schemes. Both neurometric variables contained substantial stimulus information, carried even by spikes of single barrel cortex neurons. To elucidate which type of information is actually used by the rats, we systematically compared psychometric with neurometric sensitivity based on the 2 coding schemes. Neurometric performance was calculated by using a population-encoding model incorporating the properties of our recorded neuron sample. We found that sensitivity calculated from spike counts sampled over long periods (>1 s) matched the performance of rats better than the one carried by spikes time-locked to the stimulus. We conclude that spike counts are more relevant to tactile perception when instantaneous kinematic parameters are not available

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.Cohen Veterans BioscienceRevisión por pare

Deciphering the cryptic genome: Genome-wide analyses of the rice pathogen <em>Fusarium fujikuroi</em> reveal complex regulation of secondary metabolism and novel metabolites.

The fungus Fusarium fujikuroi causes &ldquo;bakanae&rdquo; disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus&#39; interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F. fujikuroi as a rice pathogen