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Pfister, P.

Publications and source records attributed to Pfister, P..

4 recordsLinked to original sources

Evidence of elemental encoding at the olfactory periphery

How complex, multifaceted perceptual odor qualities of volatile chemicals are encoded by the olfactory system is poorly understood. We explore the receptive fields of individual odorant receptors and show how potent agonists share a consistent perceptual quality despite chemical diversity. This supports the idea that the olfactory neural connectome maintains peripheral information like odor quality through the distinct layers of the system, akin to a labeled line regime present in other sensory structures. We further observe that simple combinatorial activation of odorant receptors can generate a perceptual sum. Human olfaction may thus be shaped by the orthogonal and elemental encoding of olfactory features detected by receptor selectivity and activity. These results provide novel insights into how the brain processes olfactory information and more broadly into neural encoding during sensory processing.

neuroscience↗

Exploring dynamic brain oscillations in motor imagery and low-frequency sound

While both motor imagery (MI) and low-frequency sound listening have independently demonstrated the ability to modulate brain activity, there remains an unexplored frontier regarding the potential synergistic effects that may arise from their combined application. Any further modulation derived from this combination may be relevant for motor learning and/or rehabilitation. We conducted an experiment probing the electrophysiological activity of brain during these processes. By means of EEG, we recorded alpha and beta band power amplitude, which serve as markers of brain activity. Twenty volunteers were instructed to i) explicitly imagine finger flexion/extension movements in a kinaesthetic modality, ii) listen to low-frequency sounds, iii) imagine finger flexion while listening to low-frequency sounds, and iv) stay at rest. We observed a bimodal distribution, suggesting the presence of variability in brain activity across participants during both MI and low-frequency sound listening. One group of participants (12 individuals) displayed increased alpha power within contralateral sensorimotor and ipsilateral medial parieto-occipital regions during MI. Another group (8 individuals) exhibited a decrease in alpha and beta band power within sensorimotor areas. Interestingly, low-frequency sound listening elicited a similar pattern of brain activity within both groups. Surprisingly, the combination of MI and sound listening did not result in additional changes in alpha and beta power amplitudes compared to these processes in isolation, regardless of group. Altogether, these findings shed significant insight into the brain activity and its variability generated during MI and low-frequency sound listening. Nevertheless, it appears that the simultaneous engagement of MI and low-frequency sound listening could not further modulate alpha power amplitude, possibly due to concurrent cortical activations. This prompts us to inquire whether administering these interventions sequentially could uncover any additional modulation.

neuroscience↗

On the flexibility of the cellular amination network in E. coli

Ammonium (NH4+) is essential to generate the nitrogenous building blocks of life. It gets assimilated via the canonical biosynthetic routes to glutamate and is further distributed throughout metabolism via a network of transaminases. To study the flexibility of this network, we constructed an Escherichia coli glutamate auxotrophic strain. This strain allowed us to systematically study which amino acids serve as amine source and found that several amino acids complement the auxotrophy, either by producing glutamate via transamination reactions or by their conversion to glutamate. In this network, we identified aspartate transaminase AspC as a major connector between many amino acids and glutamate. Additionally, we extended the transaminase network by the amino acids {beta}-alanine, alanine, glycine and serine as new amine sources and identified D-amino acid dehydrogenase (DadA) as an intracellular amino acid sink removing substrates from transaminase reactions. Finally, ammonium assimilation routes producing aspartate or leucine were introduced. Our study reveals the high flexibility of the cellular amination network, both in terms of transaminase promiscuity and adaptability to new connections and ammonium entry points.

systems biology↗

ODORANT RECEPTOR INHIBITION IS FUNDAMENTAL TO ODOR ENCODING

Most natural odors are complex mixtures of many volatile components, competing to bind odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) of the nose. To date surprisingly little is known about how OR antagonism shapes neuronal representations in the periphery of the olfactory system. Here, we investigated its prevalence, the degree to which it disrupts OR ensemble activity, and its conservation across related ORs. Calcium imaging microscopy of dissociated OSNs revealed significant inhibition, often complete attenuation, of responses to indole, a commonly occurring volatile associated with both floral and fecal odors, by a set of 36 tested odorants. To confirm an OR mechanism for the observed inhibition, we performed single-cell transcriptomics on OSNs that exhibited specific response profiles to a diagnostic panel of odorants and identified the receptor Olfr743 which, when tested in vitro, recapitulated ex vivo responses. We screened ten ORs from the Olfr743 clade with 800 perfumery-related odorants spanning a range of chemical scaffolds and functional groups, over half of which (430) antagonized at least one of the ten ORs. Furthermore, OR activity outcomes were divergent rather than redundant, even for the most closely related paralogs. OR activity fitted a mathematical model of competitive receptor binding and suggests that normalization of OSN ensemble responses to odorant mixtures is the rule rather than the exception. In summary, we observed OR antagonism, inverse agonism and partial agonism occurring frequently and in a combinatorial manner. Thus, extensive receptor-mediated computation of mixture information appears to occur in the olfactory epithelium prior to transmission of odor information to the olfactory bulb.

neuroscience↗