Functionally Distinct Neuronal Ensembles within the Memory Engram.

Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.

Fast odour dynamics are encoded in the olfactory system and guide behaviour.

Odours are transported in turbulent plumes, which result in rapid concentration fluctuations1,2 that contain rich information about the olfactory scenery, such as the composition and location of an odour source2-4. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond odour pulse patterns produce distinct responses in olfactory receptor neurons. In operant conditioning experiments, mice discriminated temporal correlations of rapidly fluctuating odours at frequencies of up to 40 Hz. In imaging and electrophysiological recordings, such correlation information could be readily extracted from the activity of mitral and tufted cells-the output neurons of the olfactory bulb. Furthermore, temporal correlation of odour concentrations5 reliably predicted whether odorants emerged from the same or different sources in naturalistic environments with complex airflow. Experiments in which mice were trained on such tasks and probed using synthetic correlated stimuli at different frequencies suggest that mice can use the temporal structure of odours to extract information about space. Thus, the mammalian olfactory system has access to unexpectedly fast temporal features in odour stimuli. This endows animals with the capacity to overcome key behavioural challenges such as odour source separation5, figure-ground segregation6 and odour localization7 by extracting information about space from temporal odour dynamics.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Behavioral encoding across timescales by region-specific dopamine dynamics.

The dorsal (DS) and ventral striatum (VS) receive dopaminergic projections that control motor functions and reward-related behavior. It remains poorly understood how dopamine release dynamics across different temporal scales in these regions are coupled to behavioral outcomes. Here, we employ the dopamine sensor dLight1.3b together with multiregion fiber photometry and machine learning-based analysis to decode dopamine dynamics across the striatum during self-paced exploratory behavior in mice. Our data show a striking coordination of rapidly fluctuating signal in the DS, carrying information across dopamine levels, with a slower signal in the VS, consisting mainly of slow-paced transients. Importantly, these release dynamics correlated with discrete behavioral motifs, such as turns, running, and grooming on a subsecond-to-minute time scale. Disruption of dopamine dynamics with cocaine caused randomization of action selection sequencing and disturbance of DS-VS coordination. The data suggest that distinct dopamine dynamics of DS and VS jointly encode behavioral sequences during unconstrained activity with DS modulating the stringing together of actions and VS the signal to initiate and sustain the selected action.

Wireless monitoring of respiration with EEG reveals relationships between respiration, behavior, and brain activity in freely moving mice.

Active sampling in the olfactory domain is a fundamental aspect of mouse behavior, and there is increasing evidence that respiration-entrained neural activity outside of the olfactory system sets an important global brain rhythm. It is therefore crucial to accurately measure breathing during natural behaviors. We develop a new approach to do this in freely moving animals, by implanting a telemetry-based pressure sensor into the right jugular vein, which allows for wireless monitoring of thoracic pressure. After verifying this technique against standard head-fixed respiration measurements, we combined it with EEG and EMG recording and used evolving partial coherence analysis to investigate the relationship between respiration and brain activity across a range of experiments in which the mice could move freely. During voluntary exploration of odors and objects, we found that the association between respiration and cortical activity in the delta and theta frequency range decreased, whereas the association between respiration and cortical activity in the alpha range increased. During sleep, however, the presentation of an odor was able to cause a transient increase in sniffing without changing dominant sleep rhythms (delta and theta) in the cortex. Our data align with the emerging idea that the respiration rhythm could act as a synchronizing scaffold for specific brain rhythms during wakefulness and exploration, but suggest that respiratory changes are less able to impact brain activity during sleep. Combining wireless respiration monitoring with different types of brain recording across a variety of behaviors will further increase our understanding of the important links between active sampling, passive respiration, and neural activity.NEW & NOTEWORTHY Animals can alter their respiration rate to actively sample their environment, and increasing evidence suggests that neurons across the brain align their firing to this changing rhythm. We developed a new approach to measure sniffing in freely moving mice while simultaneously recording brain activity, and uncovered how specific cortical rhythms changed their coherence with respiration rhythm during natural behaviors and across arousal states.

Coherent olfactory bulb gamma oscillations arise from coupling independent columnar oscillators.

Spike timing-based representations of sensory information depend on embedded dynamical frameworks within neuronal networks that establish the rules of local computation and interareal communication. Here, we investigated the dynamical properties of olfactory bulb circuitry in mice of both sexes using microelectrode array recordings from slice and in vivo preparations. Neurochemical activation or optogenetic stimulation of sensory afferents evoked persistent gamma oscillations in the local field potential. These oscillations arose from slower, GABA(A) receptor-independent intracolumnar oscillators coupled by GABA(A)-ergic synapses into a faster, broadly coherent network oscillation. Consistent with the theoretical properties of coupled-oscillator networks, the spatial extent of zero-phase coherence was bounded in slices by the reduced density of lateral interactions. The intact in vivo network, however, exhibited long-range lateral interactions that suffice in simulation to enable zero-phase gamma coherence across the olfactory bulb. The timing of action potentials in a subset of principal neurons was phase-constrained with respect to evoked gamma oscillations. Coupled-oscillator dynamics in olfactory bulb thereby enable a common clock, robust to biological heterogeneities, that is capable of supporting gamma-band spike synchronization and phase coding across the ensemble of activated principal neurons.NEW & NOTEWORTHY Odor stimulation evokes rhythmic gamma oscillations in the field potential of the olfactory bulb, but the dynamical mechanisms governing these oscillations have remained unclear. Establishing these mechanisms is important as they determine the biophysical capacities of the bulbar circuit to, for example, maintain zero-phase coherence across a spatially extended network, or coordinate the timing of action potentials in principal neurons. These properties in turn constrain and suggest hypotheses of sensory coding.

Beating the heart failure odds: long-term survival after myocardial ischemia in juvenile rainbow trout.

Salmonid fish include some of the most valued cultured fish species worldwide. Unlike most other fish, the hearts of salmonids, including Atlantic salmon and rainbow trout, have a well-developed coronary circulation. Consequently, their hearts' reliance on oxygenation through coronary arteries leaves them prone to coronary lesions, believed to precipitate myocardial ischemia. Here, we mimicked such coronary lesions by subjecting groups of juvenile rainbow trout to coronary ligation, assessing histomorphological myocardial changes associated with ischemia and scarring in the context of cardiac arrhythmias using electrocardiography (ECG). Notable ECG changes resembling myocardial ischemia-like ECG in humans, such as atrioventricular blocks and abnormal ventricular depolarization (prolonged and fragmented QRS complex), as well as repolarization (long QT interval) patterns, were observed during the acute phase of myocardial ischemia. A remarkable 100% survival rate was observed among juvenile trout subjected to coronary ligation after 24 wk. Recovery from coronary ligation occurred through adaptive ventricular remodeling, coupled with a fast cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health in salmonid fish, a family particularly susceptible to cardiac diseases. Furthermore, our results provide valuable insights into comparative studies on the evolution, pathophysiology, and ontogeny of vertebrate cardiac repair and restoration.NEW & NOTEWORTHY Juvenile rainbow trout exhibit a remarkable capacity to recover from cardiac injury caused by myocardial ischemia. Recovery from cardiac damage occurs through adaptive ventricular remodeling, coupled with a rapid cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health within salmonid fishes, which are particularly susceptible to cardiac diseases.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than those of males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e. coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Although we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

When the digits don't add up: Research strategies for post-digital peacebuilding.

This article develops a post-digital perspective for the study of international peacebuilding and elaborates its merits. Contrary to narratives in policy and practice that tend to fetishize the digital, digital peacebuilding cannot be meaningfully separated from peacebuilding before digitalization. Resisting the call for a "digital turn," a post-digital lens helps to research, rewrite, and rework the digital while simultaneously staying with and moving beyond digitalization. It aims to demystify the role of digital technologies while enabling critical scrutiny of their impact on contemporary and future peacebuilding. More specifically, the post-digital helps us to (1) establish a critical distance to narratives of fast-paced innovation and progress that fetishize the digital, (2) scrutinize how digitalization compounds contemporary approaches and constellations of peacebuilding, (3) engage with the uneven temporalities of digital peacebuilding and its diverse global manifestations, (4) shed light on its real, embodied, and tangible effects on conflict-affected populations, (5) hold digitalization accountable by unearthing disillusionments and failures, (6) re-adjust our focus on human agency in the development and use of the socio-technical systems that constitute digital peacebuilding, (7) and finally, take a rhizomatic view that is concerned with how power relations make and break digitalized peacebuilding networks.

Coupling of Mouse Olfactory Bulb Projection Neurons to Fluctuating Odor Pulses.

Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension. We have shown that mice are able to discriminate odor stimuli based on their temporal structure, indicating that information contained in the temporal structure of odor plumes can be extracted by the mouse olfactory system. Here, using in vivo extracellular and intracellular electrophysiological recordings, we show that mitral cells (MCs) and tufted cells (TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odor stimuli up to at least 20 Hz. A substantial population of cell-odor pairs showed significant coupling of their subthreshold membrane potential with the odor stimulus at both 2 Hz (29/70) and the suprasniff frequency 20 Hz (24/70). Furthermore, mitral/tufted cells (M/TCs) show differential coupling of their membrane potential to odor concentration fluctuations with tufted cells coupling more strongly for the 20 Hz stimulation. Frequency coupling was always observed to be invariant to odor identity, and M/TCs that coupled well to a mixture also coupled to at least one of the components of the mixture. Interestingly, pharmacological blocking of the inhibitory circuitry strongly modulated frequency coupling of cell-odor pairs at both 2 Hz (10/15) and 20 Hz (9/15). These results provide insight into how both cellular and circuit properties contribute to the encoding of temporal odor features in the mouse olfactory bulb.SIGNIFICANCE STATEMENT Odors in the natural environment have a strong temporal structure that can be extracted and used by mice in their behavior. Here, using in vivo extracellular and intracellular electrophysiological techniques, we show that the projection neurons in the olfactory bulb can encode and couple to the dominant frequency present in an odor stimulus. Furthermore, frequency coupling was observed to be differential between mitral and tufted cells and was odor invariant but strongly modulated by local inhibitory circuits. In summary, this study provides insight into how both cellular and circuit properties modulate encoding of odor temporal features in the mouse olfactory bulb.

Sparse connectivity for MAP inference in linear models using sister mitral cells.

Sensory processing is hard because the variables of interest are encoded in spike trains in a relatively complex way. A major goal in studies of sensory processing is to understand how the brain extracts those variables. Here we revisit a common encoding model in which variables are encoded linearly. Although there are typically more variables than neurons, this problem is still solvable because only a small number of variables appear at any one time (sparse prior). However, previous solutions require all-to-all connectivity, inconsistent with the sparse connectivity seen in the brain. Here we propose an algorithm that provably reaches the MAP (maximum a posteriori) inference solution, but does so using sparse connectivity. Our algorithm is inspired by the circuit of the mouse olfactory bulb, but our approach is general enough to apply to other modalities. In addition, it should be possible to extend it to nonlinear encoding models.

Quick insights into whisky - investigating rapid and efficient methods for sensory evaluation and chemical analysis.

The evaluation of aroma properties of beverages, both analytically as well as with human sensory studies, is a challenging task and most often related to time- and cost-intensive analyses. Whisky is a spirit offering a wide variety of aroma impressions caused by a complex mixture of aroma active compounds. In the present study, methods for the efficient evaluation of aroma characteristics are evaluated for 16 whisky samples of different origins (Scotch and American). Rate all that apply (RATA) was applied as a rapid method for the sensory evaluation of whiskies. Sensory evaluation of the samples led to the determination of eight significant aroma attributes: caramel-/cream caramel-/toffee-like, vanilla-like, (canned) peach-like, phenolic, smoky, fruity, flowery and (fermented) apple-/cider-like. Chemical analysis was conducted by stir bar sorptive extraction (SBSE) coupled to gas chromatography-mass spectrometry in combination with an in-house data processing tool for semi-automated analyte detection. Through chemical analysis of the whisky samples and automated compound detection, we report over 200 mostly aroma-active volatiles. To test both approaches for their potential for sample classification, a simple classification problem (Scotch vs. American) was applied. Linear discriminant analysis (LDA) indicates both that sensory evaluation by RATA (97.86%) and the applied analytical procedure (96.94%) are suitable for the distinction between the two whisky types. In both approaches, potential markers were determined for the classification. These investigations build a solid foundation for the implementation of a versatile platform facilitating rapid and efficient aroma evaluation in various foodstuffs and beverages.

Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3.

Evasion of DNA damage-induced cell death, via mutation of the p53 tumor suppressor or overexpression of prosurvival Bcl-2 family proteins, is a key step toward malignant transformation and therapeutic resistance. We report that depletion or acute inhibition of checkpoint kinase 1 (Chk1) is sufficient to restore gamma-radiation-induced apoptosis in p53 mutant zebrafish embryos. Surprisingly, caspase-3 is not activated prior to DNA fragmentation, in contrast to classical intrinsic or extrinsic apoptosis. Rather, an alternative apoptotic program is engaged that cell autonomously requires atm (ataxia telangiectasia mutated), atr (ATM and Rad3-related) and caspase-2, and is not affected by p53 loss or overexpression of bcl-2/xl. Similarly, Chk1 inhibitor-treated human tumor cells hyperactivate ATM, ATR, and caspase-2 after gamma-radiation and trigger a caspase-2-dependent apoptotic program that bypasses p53 deficiency and excess Bcl-2. The evolutionarily conserved "Chk1-suppressed" pathway defines a novel apoptotic process, whose responsiveness to Chk1 inhibitors and insensitivity to p53 and BCL2 alterations have important implications for cancer therapy.

Live-cell lipid biochemistry reveals a role of diacylglycerol side-chain composition for cellular lipid dynamics and protein affinities.

Every cell produces thousands of distinct lipid species, but insight into how lipid chemical diversity contributes to biological signaling is lacking, particularly because of a scarcity of methods for quantitatively studying lipid function in living cells. Using the example of diacylglycerols, prominent second messengers, we here investigate whether lipid chemical diversity can provide a basis for cellular signal specification. We generated photo-caged lipid probes, which allow acute manipulation of distinct diacylglycerol species in the plasma membrane. Combining uncaging experiments with mathematical modeling, we were able to determine binding constants for diacylglycerol-protein interactions, and kinetic parameters for diacylglycerol transbilayer movement and turnover in quantitative live-cell experiments. Strikingly, we find that affinities and kinetics vary by orders of magnitude due to diacylglycerol side-chain composition. These differences are sufficient to explain differential recruitment of diacylglycerol binding proteins and, thus, differing downstream phosphorylation patterns. Our approach represents a generally applicable method for elucidating the biological function of single lipid species on subcellular scales in quantitative live-cell experiments.

Improved protocol for the radiosynthesis of [18 F]FTC-146: A potent and selective sigma-1 receptor radioligand.

[18 F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4-7% was not satisfactory to us, and efforts were made to improve it. Herein, we describe an improved approach for the radiosynthesis of [18 F]FTC-146 resulting in a RCY, which is sevenfold higher than that previously reported. A tosylate precursor was synthesized and radio-fluorination experiments were performed via aliphatic nucleophilic substitution reactions using either K[18 F]F-Kryptofix®222 (K2.2.2 )-carbonate system or tetra-n-butylammonium [18 F]fluoride ([18 F]TBAF). Several parameters affecting the radiolabeling reaction such as solvent, 18 F-fluorination agent with the corresponding amount of base, labeling time, and temperature were investigated. Best labeling reaction conditions were found to be [18 F]TBAF and acetonitrile as solvent at 100°C. The new protocol was then translated to an automated procedure using a FX2 N synthesis module. Finally, the radiotracer reproducibly obtained with RCYs of 41.7 ± 4.4% in high radiochemical purity (>98%) and molar activities up to 171 GBq/µmol.

Freedom of choice and the tobacco endgame.

Endgame proposals strive for a tobacco-free (or at least cigarette-free) society. Some endgame proposals are radical and include, for example, a complete ban on cigarettes. Setting aside empirical worries, one worry is ethical: would such proposals not go too far in interfering with individual freedom? I argue that concerns around freedom do not speak against endgame proposals, including strong proposals such as a ban on cigarettes. I first argue that when balancing freedom with public health goals in tobacco control, the latter win out. But I also argue that, in principle, a concern with freedom itself already justifies endgame measures. First, such measures can increase people's lifetime freedom, that is, the freedom they have across their entire lives. Second, such measures can facilitate a better interpersonal distribution of freedom by increasing aggregate societal freedom and by reducing inequalities. Overall, freedom does not preclude strict tobacco control but supports it.

Validity of a Smartphone Application in Calculating Measures of Heart Rate Variability.

The purpose of the current study was to determine the concurrent validity of the Elite HRV smartphone application when calculating heart rate variability (HRV) metrics in reference to an independent software criterion. A total of 5 minutes of R−R interval and natural log of root mean square of the successive differences (lnRMSSD) resting HRV data were simultaneously collected using two Polar H10 heart rate monitors (HRMs) in both the seated and supine positions from 22 participants (14 males, 8 females). One H10 HRM was paired with a Polar V800 watch and one with the Elite HRV application. When no artifact correction was applied, significant, but small, differences in the lnRMSSD data were observed between the software in the seated position (p = 0.022), and trivial and nonstatistically significant differences were observed in the supine position (p = 0.087). However, significant differences (p > 0.05) in the lnRMSSD data were no longer identifiable in either the seated or the supine positions when applying Very Low, Low, or Automatic artifact-correction filters. Additionally, excellent agreements (ICC3,1 = 0.938 − 0.998) and very strong to near-perfect (r = 0.889 − 0.997) relationships were observed throughout all correction levels. The Elite HRV smartphone application is a valid tool for calculating resting lnRMSSD HRV metrics.

Unraveling the Complexity of Supramolecular Copolymerization Dictated by Triazine-Benzene Interactions.

Supramolecular copolymers formed by the noncovalent synthesis of multiple components expand the complexity of functional molecular systems. However, varying the composition and microstructure of copolymers through tuning the interactions between building blocks remains a challenge. Here, we report a remarkable discovery of the temperature-dependent supramolecular copolymerization of the two chiral monomers 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tribenzamide (S-T) and 4,4',4″-(benzene-1,3,5-triyl)tribenzamide (S-B). We first demonstrate in the homopolymerization of the two individual monomers that a subtle change from the central triazine to benzene in the chemical structure of the monomers significantly affects the properties of the resulting homopolymers in solution. Homopolymers formed by S-T exhibit enhanced stability in comparison to S-B. More importantly, through a combination of spectroscopic analysis and theoretical simulation, we reveal the complex process of copolymerization: S-T aggregates into homopolymers at elevated temperature, and upon slow cooling S-B gradually intercalates into the copolymers, to finally give copolymers with almost 80% alternating bonds at 10 °C. The formation of the predominantly alternating copolymers is plausibly contributed by preferred heterointeractions between triazine and benzene cores in S-T and S-B, respectively, at lower temperatures. Overall, this work unravels the complexity of a supramolecular copolymerization process where an intermediate heterointeraction (higher than one homointeraction and lower than the other homointeraction) presents and proposes a general method to elucidate the microstructures of copolymers responsive to temperature changes.

Screening Methanol Poisoning with a Portable Breath Detector.

Methanol poisoning outbreaks after consumption of adulterated alcohol frequently overwhelm health care facilities in developing countries. Here, we present how a recently developed low-cost and handheld breath detector can serve as a noninvasive and rapid diagnostic tool for methanol poisoning. The detector combines a separation column and a micromachined chemoresistive gas sensor fully integrated into a device that communicates wirelessly with a smartphone. The performance of the detector is validated with methanol-spiked breath of 20 volunteers (105 breath samples) after consumption of alcoholic beverages. Breath methanol concentrations were quantified accurately within 2 min in the full breath-relevant range (10-1000 ppm) in excellent agreement (R2 = 0.966) with benchtop mass spectrometry. Bland-Altman analysis revealed sufficient limits of agreement (95% confidence intervals), promising to indicate reliably the clinical need for antidote and hemodialysis treatment. This simple-in-use detector features high diagnostic capability for accurate measurement of methanol in spiked breath, promising for rapid screening of methanol poisoning and assessment of severity. It can be applied readily by first responders to distinguish methanol from ethanol poisoning and monitor in real time the subsequent hospital treatment.

Spatial information from the odour environment in mammalian olfaction.

The sense of smell is an essential modality for many species, in particular nocturnal and crepuscular mammals, to gather information about their environment. Olfactory cues provide information over a large range of distances, allowing behaviours ranging from simple detection and recognition of objects, to tracking trails and navigating using odour plumes from afar. In this review, we discuss the features of the natural olfactory environment and provide a brief overview of how odour information can be sampled and might be represented and processed by the mammalian olfactory system. Finally, we discuss recent behavioural approaches that address how mammals extract spatial information from the environment in three different contexts: odour trail tracking, odour plume tracking and, more general, olfactory-guided navigation. Recent technological developments have seen the spatiotemporal aspect of mammalian olfaction gain significant attention, and we discuss both the promising aspects of rapidly developing paradigms and stimulus control technologies as well as their limitations. We conclude that, while still in its beginnings, research on the odour environment offers an entry point into understanding the mechanisms how mammals extract information about space.