Biology subjects

Slezia, A.

Publications and source records attributed to Slezia, A..

3 recordsLinked to original sources

bioRxiv2023

Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

Studying animal models furthers our understanding of Parkinsons disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinsons disease in mice. Highlights- Unilateral striatal 6-OHDA injection caused an early onset dose-dependent behavioral deficit in mice - Behavioral deficit manifested as mild impairment of locomotion and locomotive movement initialization - Behavioral changes were accompanied by moderate, dose-dependent loss of SNc dopaminergic neurons - Behavioral changes were paralleled by ultrastructural alterations of SNc dopaminergic neurons

neuroscience↗

bioRxiv2019

In vivo characterization of neurophysiological diversity in the lateral supramammillary nucleus during hippocampal sharp-wave ripples of adult rats

The extent of the networks that control the genesis and modulation of hippocampal sharp wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R unchanged according to whether or not they increased their firing during SPW-Rs. We show that lSuM SPW-R-active neurons increase their firing prior SPW-Rs peak power and prior hippocampal pyramidal cell activation. Moreover, lSuM SPW-R-active neurons show increased firing activity during theta and slow oscillations as compared to unchanged-neurons. SPW-R-active neurons are more active during high peak power SPW-Rs, whereas SPW-R-unchanged neurons are more active during long SPW-Rs. These results suggest that a sub-population of lSuM neurons can interact with the hippocampus during SPW-Rs, raising the possibility that the lSuM may modulate memory consolidation.

neuroscience↗

bioRxiv2018

NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording.

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.\n\nIn this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10{micro}m wide, 1.5{micro}m thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35{micro}m microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.\n\nThis research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.

neuroscience↗