Biology subjects

Prakash, S. S.

Publications and source records attributed to Prakash, S. S..

3 recordsLinked to original sources

bioRxiv2023

Dissociation of attentional state and behavioral outcome using local field potentials

Successful behavior depends on attentional state and other factors related to decision-making, which may modulate neuronal activity differently. Here, we investigated whether attentional state and behavioral outcome (i.e., whether a target is detected or missed) are distinguishable using the power and phase of local field potential (LFP) recorded bilaterally from area V4 of monkeys performing a cued visual attention task. To link each trials outcome to pairwise measures of attention that are typically averaged across trials, we used several methods to obtain single-trial estimates of spike count correlation and phase consistency. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase in attentional/behavioral discriminability, although single-trial gamma phase consistency provided reasonably high attentional discriminability. Our results suggest a dissociation between the neuronal mechanisms that regulate attentional focus and behavioral outcome.

neuroscience↗

bioRxiv2022

Synaptojanin1 regulates lysosomal functions in ventral midbrain neurons

A major pathological hallmark of Parkinsons Disease (PD) is the manifestation of Lewy bodies comprised of alpha-synuclein (-syn). The accumulation of -syn enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency (Synj1+/-) leads to PD-like behavioral and pathological changes in mice, including the accumulation of the autophagy substrate p62 and pathological -syn proteins in the midbrain (MB) and striatum. In this study, we aim to investigate the neuronal degradation pathway using the Synj1+/- MB culture as a model. Our data suggests that autophagy flux and cumulative autophagosome formation is unaltered at baseline in Synj1+/- MB neurons. However, lysosome number is reduced with a similar decrease in lysosomal proteins, including LAMP1, LAMP2, and LAMP2A. Lysosomes are hyperacidified with enhanced enzymatic activity in Synj1+/- MB neurons. Using a combination of light and electron microscopy, we show that lysosomal changes are primarily associated with a lack of SAC1 activity. Consistently, expressing the SYNJ1 R258Q mutant in N2a cells reduces the lysosome number. Interestingly, the lysosomal defects in Synj1+/- neurons does not impact the clearance of exogenously expressed wild-type -syn; however, the clearance of -syn A53T was impaired in the axons of Synj1+/- MB neurons. Taken together, our results suggest axonal vulnerability to lysosomal defects in Synj1 deficient MB neurons. Significance StatementIn the study, Zhu et al. discovered a previously uncharacterized role of Synj1 in regulating lysosomal number, protein, and acidity in ventral midbrain neurons. These alterations are associated with a specific impairment in the clearance of -syn A53T, but not WT -syn in axons, suggesting an essential role of Synj1 in axonal degradative capacity under pathological stress. This work in cultured mammalian neurons complements recent research efforts in Drosophila, C. elegans and zebra fish, and provides a novel insight for the role Synj1 in neuronal autolysosomal function.

neuroscience↗

bioRxiv2020

Decoding of attentional state using high-frequency local field potential is as accurate as using spikes

Local field potentials (LFPs) in visual cortex are reliably modulated when the subjects focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spiking activity. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spiking responses was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found that LFPs during neutral cueing were intermediate between cued and uncued conditions, and, for a single electrode, attention was more discriminable using high frequency (>30 Hz) LFP power than spikes. Surprisingly, spikes did not outperform LFPs even when discriminability was computed using multiple electrodes. These results constrain the spatial scale attention operates over and highlight the usefulness of LFPs in studying attention.

neuroscience↗