Biology subjects

Chernysheva, M.

Publications and source records attributed to Chernysheva, M..

3 recordsLinked to original sources

bioRxiv2022

Locus Coeruleus firing patterns selectively modulate brain activity and dynamics

Noradrenaline (NA) release from the brainstem nucleus locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, thus modulating multiple behavioural states. NA release is mediated by both tonic and burst-like neuronal LC activity. However, it remains unknown whether the functional changes in downstream projection areas depend on these firing patterns. Using optogenetics, pupillometry, photometry, and functional MRI in mice, we show that tonic and burst LC firing patterns elicit brain responses that are specific to the activation frequency and temporal pattern. Tonic activation of the LC evokes nonlinear responses in prefrontal, limbic, and cerebellar regions, in line with the proposed inverted-U relationship between LC activity and behaviour. We further demonstrate that LC activity enhances network integration and acts as a facilitator of brain state transitions, hence increasing brain flexibility. Together, these findings reveal how the LC-NA system achieves a nuanced regulation of global circuit operations.

neuroscience↗

bioRxiv2021

Striatum-projecting prefrontal cortex neurons support working memory maintenance

The medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC[->]dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC[->]dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC[->]dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC[->]dmStr pathway activity--via pharmacological suppression of HCN1 or by optogenetic activation during the delay-- alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of >50% mPFC[->]dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

neuroscience↗

bioRxiv2018

High-density multi-fiber photometry for studying large-scale brain circuit dynamics

Animal behavior originates from neuronal activity distributed and coordinated across brain-wide networks. However, techniques to assess large-scale brain circuit dynamics in behaving animals remain limited. Here we present compact, high-density arrays of optical fibers that can be chronically implanted into the mammalian brain, enabling multi-fiber photometry as well as optogenetic perturbations across many regions. In mice engaged in a texture discrimination task we achieved simultaneous photometric calcium recordings from networks of 12 to 48 brain regions, including striatal, thalamic, hippocampal, and cortical areas. Furthermore, we optically perturbed specific subsets of regions in VGAT-ChR2 mice by using a spatial light modulator to address the respective fiber channels. Perturbation of ventral thalamic nuclei caused distributed network modulation and behavioral deficits. Finally, we demonstrate multi-fiber photometry in freely moving animals, including simultaneous recordings from two mice during social interaction. Thus, high-density multi-fiber arrays are simple, low-cost, and versatile tools that open novel ways to investigate large-scale brain dynamics during behavior.

neuroscience↗