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Suarez, L. M.

Publications and source records attributed to Suarez, L. M..

2 recordsLinked to original sources
bioRxiv2024

GBA1 MUTATIONS ALTER THE PHENOTYPE AND BEHAVIOUR OF DOPAMINERGIC NEURONS IN PARKINSON DISEASE, INFLUENCING VGLUT2 AND CRYAB EXPRESSION

Mutations in the GBA1 gene are major risk factors for Parkinso[n]s disease (PD), but their role in PD pathology is not fully understood. The impact of GBA1 mutations was investigated in dopamine (DA) neurons obtained from induced pluripotent stem cells (iPSCs) derived from PD patients carrying the N370S or L444P GBA1 mutation. DA neurons co-expressing TH and VGLUT2 were detected in the cultures, and their number and/or expression of VGLUT2/SLC17A6 mRNA was markedly reduced in both N370S and L444P cultures compared to controls. A significant increase in the firing rate of N370S neurons was found, whereas evoked dopamine release was stronger from neurons carrying either mutation. Furthermore, mutant neurons accumulated abundant degenerative structures, and there was a significant accumulation of -synuclein aggregates in N370S neurons. Notably, a significant upregulation of the chaperone CRYAB/HSPB5/alpha-crystallin-B was found early in DA neuron differentiation and in the substantia nigra of PD patients. Our findings indicate that N370S and L444P GBA1 mutations impair midbrain DA neurons expressing VGLUT2, and provoke molecular, functional and structural changes, possibly involved in PD pathology.

neuroscience↗
bioRxiv2024

The spiking output of the mouse olfactory bulb encodes large-scale temporal features of natural odor environments

In natural odor environments, odor travels in plumes. Odor concentration dynamics change in characteristic ways across the width and length of a plume. Thus, spatiotemporal dynamics of plumes have informative features for animals navigating to an odor source. Population activity in the olfactory bulb (OB) has been shown to follow odor concentration across plumes to a moderate degree (Lewis et al., 2021). However, it is unknown whether the ability to follow plume dynamics is driven by individual cells or whether it emerges at the population level. Previous research has explored the responses of individual OB cells to isolated features of plumes, but it is difficult to adequately sample the full feature space of plumes as it is still undetermined which features navigating mice employ during olfactory guided search. Here we released odor from an upwind odor source and simultaneously recorded both odor concentration dynamics and cellular response dynamics in awake, head-fixed mice. We found that longer timescale features of odor concentration dynamics were encoded at both the cellular and population level. At the cellular level, responses were elicited at the beginning of the plume for each trial, signaling plume onset. Plumes with high odor concentration elicited responses at the end of the plume, signaling plume offset. Although cellular level tracking of plume dynamics was observed to be weak, we found that at the population level, OB activity distinguished whiffs and blanks (accurately detected odor presence versus absence) throughout the duration of a plume. Even [~]20 OB cells were enough to accurately discern odor presence throughout a plume. Our findings indicate that the full range of odor concentration dynamics and high frequency fluctuations are not encoded by OB spiking activity. Instead, relatively lower-frequency temporal features of plumes, such as plume onset, plume offset, whiffs, and blanks, are represented in the OB.

neuroscience↗