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Srikanth, S.

Publications and source records attributed to Srikanth, S..

2 recordsLinked to original sources

Theta oscillations in the prefrontal-hippocampal circuit do not couple to respiration-related oscillations

Oscillatory activity is thought to coordinate neural computations across brain regions, and theta oscillations are critical for learning and memory. Because the frequency of respiratory-related oscillations (RROs) in rodents can overlap with the frequency of theta in the prefrontal cortex (PFC) and the hippocampus, we asked whether odor-cued working memory may be supported by coupling between these two oscillations. We first confirmed that RROs are propagated to the hippocampus and PFC and that RRO frequency overlaps with canonical theta frequency. However, we found low coherence between RROs and local theta oscillations in the hippocampus-PFC network when the two types of oscillations overlapped in frequency. This effect was observed during all behavioral phases including during movement and while odors were actively sampled when stationary. Despite the similarity in frequency, RROs and theta oscillations therefore appear to be limited to supporting computation in distinct networks, which suggests that sustained long-range coordination between oscillation patterns that depend on separate pacemakers is not necessary to support at least one type of working memory.

neuroscience↗

ORAI1 establishes resistance to SARS-CoV-2 infection by regulating tonic type I interferon signaling

ORAI1 and STIM1 are the critical mediators of store-operated Ca2+ entry by acting as the pore subunit and an endoplasmic reticulum-resident signaling molecule, respectively. In addition to Ca2+ signaling, STIM1 is also involved in regulation of a cytosolic nucleic acid sensing pathway. Using ORAI1 and STIM1 knockout cells, we examined their contribution to the host response to SARS-CoV-2 infection. STIM1 knockout cells showed strong resistance to SARS-CoV-2 infection due to enhanced type I interferon response. On the contrary, ORAI1 knockout cells showed high susceptibility to SARS-CoV-2 infection as judged by increased expression of viral proteins and a high viral load. Mechanistically, ORAI1 knockout cells showed reduced homeostatic cytoplasmic Ca2+ concentration and severe impairment in tonic interferon signaling. Transcriptome analysis showed downregulation of multiple cellular defense mechanisms, including antiviral signaling pathways in ORAI1 knockout cells, which are likely due to reduced expression of the Ca2+-dependent transcription factors of the activator protein 1 (AP-1) family and MEF2C. Our results identify a novel role of ORAI1-mediated Ca2+ signaling in regulating the baseline type I interferon level, which is a determinant of host resistance to SARS-CoV-2 infection.

microbiology↗