Biology subjects

Pawliszyn, J.

Publications and source records attributed to Pawliszyn, J..

4 recordsLinked to original sources

bioRxiv2026

Cognitive engagement induces area-specific fingerprints of dopamine, acetylcholine, serotonin, glutamate and GABA in prefrontal cortex and striatum

Cholinergic, dopaminergic and serotonergic neuromodulation has pervasive effects on circuit functions in prefrontal cortex (PFC) and striatum and interact with glutamatergic and GABAergic transmission. But how these neurochemicals interact during cognitive engagement is largely unknown and inferred from studying few neuromodulators at a time. Here, we sampled the extracellular availabilities of five neurochemicals in the PFC and striatum of nonhuman primates and tested how they changed when subjects switched from rest to engage in a cognitive set shifting task using miniaturized probes for diffusion-based solid-phase microextraction. Cognitive engagement was best predicted by GABAergic and cholinergic changes in the PFC, and dopaminergic and cholinergic changes in the striatum. Glutamate co-modulated with acetylcholine across states in both the PFC and striatum, while serotonin changes in PFC and striatum correlated consistent with common external modulation. These findings document an area-specific multi-neuromodulatory fingerprint of an adaptive cognitive state in the fronto-striatal network of the nonhuman primate brain. TeaserEngaging in a cognitive task reshapes neurochemical profiles across the fronto-striatal network of the primate brain

neuroscience↗

bioRxiv2021

Dose-dependent dissociation of pro-cognitive effects of donepezil on attention and cognitive flexibility in rhesus monkeys

BACKGROUNDDonepezil exerts pro-cognitive effects by non-selectively enhancing acetylcholine (ACh) across multiple brain systems. The brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose-ranges for donepezil to enhance the cognitive domains of attention and flexible learning. METHODSTo test for dose-specific effects of donepezil on different cognitive domains we devised a multi-task paradigm for nonhuman primates (NHPs) that assessed attention and cognitive flexibility. NHPs received either vehicle or variable doses of donepezil prior to task performance. We measured donepezil intracerebral and how strong it prevented the breakdown of ACh within prefrontal cortex and anterior striatum using solid-phase-microextraction neurochemistry. RESULTSThe highest administered donepezil dose improved attention and made subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum. CONCLUSIONSThe donepezil dose for maximally improving attention functions differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in the major brain systems supporting these cognitive functions. Thus, the non-selective acetylcholine esterase inhibitor donepezil inherently trades improvement in the attention domain for improvement in the cognitive flexibility domain at a given dose range.

pharmacology and toxicology↗

bioRxiv2019

Simulation-based comprehensive study of batch effects in metabolomics studies

Batch effects will influence the interpretation of metabolomics data. In order to avoid misleading results, batch effects should be corrected and normalized prior to statistical analysis. Metabolomics studies are usually performed without targeted compounds (e.g., internal standards) and it is a challenging task to validate batch effects correction methods. In addition, statistical properties of metabolomics data are quite different from genomics data (where most of the currently used batch correction methods have originated from). In this study, we firstly analyzed already published metabolomics datasets so as to summarize and discuss their statistical properties. Then, based on available datasets, we developed novel statistical properties-based in silico simulations of metabolomics peaks intensity data so as to analyze the influence of batch effects on metabolomic data with the use of currently available batch correction strategies. Overall, 252000 batch corrections on 14000 different in silico simulated datasets and related differential analyses were performed in order to evaluate and validate various batch correction methods. The obtained results indicate that log transformations strongly influence the performance of all investigated batch correction methods. False positive rates increased after application of batch correction methods with almost no improvement on true positive rates among the analyzed batch correction methods. Hence, in metabolomic studies it is recommended to implement preliminary experiments to simulate batch effects from real data in order to select adequate batch correction method, based on a given distribution of peaks intensity. The presented study is reproducible and related R package mzrtsim software can be found online (https://github.com/yufree/mzrtsim).

bioinformatics↗

bioRxiv2019

Multi-Neuromodulator Measurements across Fronto-Striatal Network Areas of the Behaving Macaque using Solid-Phase Microextraction

Different neuromodulators rarely act independent from each other to modify neural processes but are instead co-released, gated, or modulated. To understand this interdependence of neuromodulators and their collective influence on local circuits during different brain states, it is necessary to reliably extract local concentrations of multiple neuromodulators in vivo. Here we describe results using solid phase microextraction (SPME), a method providing sensitive, multi-neuromodulator measurements. SPME is a sampling method that is coupled with mass spectrometry to quantify collected analytes. Reliable measurements of glutamate, dopamine, acetylcholine and choline were made simultaneously within frontal cortex and striatum of two macaque monkeys (Macaca mulatta) during goal-directed behavior. We find glutamate concentrations several orders of magnitude higher than acetylcholine and dopamine in all brain regions. Dopamine was reliably detected in the striatum at tenfold higher concentrations than acetylcholine. Acetylcholine and choline concentrations were detected with high consistency across brain areas, within monkeys and between monkeys. These findings illustrate that SPME microprobes provide a versatile novel tool to characterize multiple neuromodulators across different brain areas in vivo to understand the interdependence and co-variation of neuromodulators during goal directed behavior. Such data will be important to better distinguish between different behavioral states and characterize dysfunctional brain states that may be evident in psychiatric disorders.

neuroscience↗