Biology subjects

Filimontseva, A.

Publications and source records attributed to Filimontseva, A..

3 recordsLinked to original sources

bioRxiv2026

Location and mapping of the human rostromedial tegmental nucleus and associated midbrain inhibitory nuclei regulating dopamine neurons

Animal experiments reveal distinct GABAergic cell clusters within the dopaminergic midbrain regions in the rostromedial tegmental nucleus (RMTg) and retrorubral fields (RRF) that have yet to be clearly defined in humans. These neurons send prominent inhibitory projections to dopaminergic neurons in the substantia nigra and ventral tegmental area that impact motor, reward and threat processing. We have identified GABAergic RMTg and RRF cell clusters in 6{micro}m formalin-fixed paraffin-embedded transverse human midbrain sections from ten control cases obtained from the Sydney Brain Bank using immunohistochemistry for GABA and tyrosine hydroxylase. We determined the location and cell size of RMTg and RRF GABAergic neurons, further mapping these cell cluster in transverse 50{micro}m thick cresyl violet stained serial midbrain sections (every 750{micro}m) from previously published controls (Halliday et al. 1990a). GABAergic neurons were cytoarchitecturally distinct, with the largest GABAergic neurons in the RRF, followed by RMTg neurons which were larger than GABAergic neurons in the well-defined interpedunclular nucleus (Kruskal-Wallis test, p<0.0001). RMTg and RRF GABAergic neurons first appear in caudal transverse midbrain sections approximately 38mm above the obex. RMTg moves rostrally and medially from underneath the decussation of the superior cerebellar peduncle to just lateral to the interpeduncular nucleus. The RRF cluster also moves rostrally and medially to the parabrachial pigmented nucleus (PBP) just under the red nucleus. The GABAergic neurons in RMTg and RRF/PBP that modulate dopamine neuronal excitability have distinct morphologies in humans. Identifying these inhibitory neurons is key to evaluating their role in neurodegenerative diseases.

neuroscience↗

bioRxiv2025

Standardised TruAI automated quantification of intracellular neuromelanin granules in human brain tissue sections

AimsTo standardise and automate the quantitation of human-unique neuromelanin granules in catecholamine neurons in post-mortem tissue sections from healthy individuals at different ages to understand any changes in these granules with age. Methods5-6 {micro}m-thick fixed and paraffin-embedded transverse midbrain tissue sections were supplied from 47 cases from three brain banks following ethical approvals. Sections were prepared and automated digital images acquired. Standardisation and automation of the quantification of neuromelanin granules was performed using the TruAI feature of the Olympus VS200 desktop platform. Comparisons between stained and unstained sections as well as correlations with age were performed. ResultsThe automated platform reliably identified both stained and unstained intracellular neuromelanin granules and extracellular pigments, showing high reproducibility in measurements across laboratories using different tissue processing methods. Extraneuronal pigments were significantly smaller than intracellular neuromelanin granules. Sections processed for haematoxylin and eosin staining impacted the size and colour of both neuromelanin and the neurons containing neuromelanin. Haematoxylin made neuromelanin bluer, and the increased tissue processing made the intracellular area occupied by neuromelanin smaller in younger people. There was an increase in neuromelanin optical density and colour change (browner) with age. ConclusionsThe TruAI automated platform reliably quantifies individual neuromelanin granules in catecholamine neurons. Extraneuronal pigments are considerably smaller in size than intracellular neuromelanin, and intracellular neuromelanin changes its properties with age. The darkening and colour change of intracellular neuromelanin suggests an increase in eumelanin over time in healthy individuals. These changes can be reliably identified using the automated platform. Key pointsO_LIStandardised, reliable TruAI automated quantitation of intracellular neuromelanin granules in human brain sections gives novel insights into their structure and function C_LIO_LIExtraneuronal pigments, including neuromelanin granules released from dying pigmented neurons, are significantly smaller than intracellular neuromelanin granules C_LIO_LIIntracellular neuromelanin granules change their properties with healthy ageing becoming darker, consistent with more antioxidant eumelanin C_LI

neuroscience↗

bioRxiv2019

Aversive learning strengthens episodic memory in both adolescents and adults

Adolescence is often filled with positive and negative emotional experiences that may change how individuals remember and respond to stimuli in their environment. In adults, aversive events can both enhance memory for associated stimuli as well as generalize to enhance memory for unreinforced but conceptually related stimuli. The present study tested whether learned aversive associations similarly lead to better memory and generalization across a category of stimuli in adolescents. Participants completed an olfactory Pavlovian category conditioning task in which trial-unique exemplars from one of two categories were partially reinforced with an aversive odor. Participants then returned 24-hours later to complete a surprise recognition memory test. We found better corrected recognition memory for the reinforced versus the unreinforced category of stimuli in both adults and adolescents. Further analysis revealed that enhanced recognition memory was driven specifically by better memory for the reinforced exemplars. Autonomic arousal during learning was also related to subsequent memory. These findings build on previous work in adolescent and adult humans and rodents showing comparable acquisition of aversive Pavlovian conditioned responses across age groups and demonstrate that memory for stimuli with an acquired aversive association is enhanced in both adults and adolescents.

animal behavior and cognition↗