Biology subjects

van Hulten, J. A.

Publications and source records attributed to van Hulten, J. A..

3 recordsLinked to original sources

bioRxiv2025

Perfect imperfections: seeking molecular and cellular asymmetries in the mouse brain

Although perfect symmetry is a mathematical ideal, many Bilateria exhibit left-right asymmetries of body, brain and behavior that are adaptive 1-3. In the human brain, various aspects of cognition are lateralized, including language 4 and handedness 5, which rely on left hemisphere dominance in most people. Brain hemispheric specialization can support parallel processing, neural efficiency, and action selection 3,6, while atypical structural or functional asymmetries are often found in neuropsychiatric disorders 7-10. Mice may be useful models for studying brain asymmetry because they show hemispheric differences of structure 11,12 and neurophysiology 13, but the extent to which molecular and cellular differences are involved remains unknown. We applied spatial transcriptomics with single molecule resolution to coronal sections from 31 adult mouse brains, to assess left-right differences of gene expression and cell types. Sections were chosen to capture the hippocampus and auditory cortex, as these two regions have shown the most prior evidence for functional asymmetry 13-15. In the hippocampus, Crhr1 (Corticotropin-Releasing Hormone Receptor 1) was more highly expressed in the pyramidal layers of CA1, CA3 and the dentate gyrus of the left hemisphere compared to the right. In the auditory cortex, three principal components capturing transcriptomic variation showed hemispheric differences, including prominent contributions from genes that have shown associations with human brain asymmetry. Overall cellular density and cell type proportions generally showed no significant hemispheric differences, with Car3 cortical excitatory neurons showing the most laterality. The transcriptional left-right differences that we found may relate to functional asymmetries for learning, memory and hearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/675542v1_ufig1.gif" ALT="Figure 1"> View larger version (119K): org.highwire.dtl.DTLVardef@1530502org.highwire.dtl.DTLVardef@16dd244org.highwire.dtl.DTLVardef@107950corg.highwire.dtl.DTLVardef@ca52a3_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMolecular and cellular basis of functional brain asymmetry is barely known C_LIO_LISpatial transcriptomics with cellular resolution applied to mouse brain coronal sections C_LIO_LIGenes implicated in human brain asymmetry showed hemispheric differences in mice C_LIO_LINo hemispheric differences of cell type abundances C_LI

neuroscience↗

bioRxiv2020

Low-cost and versatile electrodes for extracellular chronic recordings in rodents

Electrophysiological data are used to investigate fundamental properties of brain function, its relation to cognition, and its dysfunction in diseases. The development of reliable and open-source systems for electrophysiological data acquisition is decreasing the total cost of constructing and operating an electrophysiology laboratory, and facilitates low-cost methods to extract and analyze the data (Siegle et al., 2017). Here we detail our method of building custom-designed low-cost electrodes. These electrodes can be customized and manufactured by any researcher to address a broad set of research questions, further decreasing the final cost of an implanted animal. Finally, we present data showing such an electrode has a good signal quality to record LFP.

neuroscience↗

bioRxiv2019

Action of cocaine involves depletion of dopaminergic and serotonergic storage vesicles

Cocaine is known to increase the extracellular levels of dopamine (DA) and serotonin (5-HT) by inhibiting the neuronal reuptake of these monoamines. However, individuals with reduced monoamine reuptake transporter expression do not display a reduction in cocaine intake, suggesting that a mechanism other than inhibition of monoamine reuptake contributes to the rewarding and addictive effects of the psychostimulant. Here we report that cocaine depletes the dopaminergic and serotonergic storage vesicles of the rat nucleus accumbens. This cocaine-induced vesicle depletion gave rise to acute increases in the extracellular levels of DA and 5-HT, which in turn correlated with monoamine-type-specific changes in behavior. Both the neurochemical and behavioral responses to cocaine varied among individual animals, which was not due to individual differences in the reuptake of DA and 5-HT, but rather to individual differences in their vesicular release. Furthermore, we found that reserpine-induced depletion of storage vesicles reduced both short and long access cocaine self-administration, and the degree of reduction was linked to the vesicular storage capacity of the animals. In conclusion, we demonstrate a novel mechanism by which cocaine increases the extracellular concentrations of accumbal DA and 5-HT, namely via release from storage vesicles. Furthermore, individual differences in cocaine-induced vesicular monoamine release shape individual differences in not only the acute behavioral and neurochemical effects of the stimulant, but also in its intake. Thus, intracellular storage vesicles represent an attractive novel drug target to combat psychostimulant addiction.

neuroscience↗