Biology subjects

Libby, A.

Publications and source records attributed to Libby, A..

3 recordsLinked to original sources

bioRxiv2023

Multiplexed Subspaces Route Neural Activity Across Brain-wide Networks

Cognition is flexible. Behaviors can change on a moment-by-moment basis. Such flexibility is thought to rely on the brains ability to route information through different networks of brain regions in order to support different cognitive computations. However, the mechanisms that determine which network of brain regions is engaged are unknown. To address this, we combined cortex-wide calcium imaging with high-density electrophysiological recordings in eight cortical and subcortical regions of mice. Different dimensions within the population activity of each brain region were functionally connected with different cortex-wide subspace networks of regions. These subspace networks were multiplexed, allowing a brain region to simultaneously interact with multiple independent, yet overlapping, networks. Alignment of neural activity within a region to a specific subspace network dimension predicted how neural activity propagated between regions. Thus, changing the geometry of the neural representation within a brain region could be a mechanism to selectively engage different brain-wide networks to support cognitive flexibility.

neuroscience↗

bioRxiv2021

Protein sensors of bacterial kinase activity reveal antibiotic-dependent kinase activation in single cells

A lack of direct single-cell readouts for bacterial kinase activity remains a major barrier to our understanding of most signaling systems. At the single-cell-level, protein kinase activity is typically inferred by the activity of downstream transcriptional reporters. Complicating this approach in vivo, promoters are often co-regulated by several pathways, making the activity of a specific kinase difficult to deconvolve. Here, we have designed and constructed new, direct and specific sensors of bacterial kinase activity, including FRET-based sensors, as well as a synthetic transcription factor that responds to phosphorylation. We demonstrate the utility of these reporters in measuring kinase activity in population-based and single-cell assays during various growth phases and antibiotic treatments. These sensors respond to a highly conserved bacterial Ser/Thr kinase, PrkC that has no known dedicated transcription factor and whose regulon is known to be convolved with an essential signaling system. We used these new sensors to measure PrkC activity in colonies, bulk culture, and single cells. Together these new sensors provide evidence for considerable heterogeneity in PrkC activity in actively growing populations. We further demonstrate that PrkC activity increases in response to a cell-wall active antibiotic that blocks the late steps in peptidoglycan synthesis (cefotaxime), but not the early steps (fosfomycin). This is consistent with a model where PrkC senses and responds to blocks in the extracellular steps in cell wall synthesis. As the design of these phosphorylation sensors is modular, we anticipate that this work may have broad applications to other bacterial signaling systems in the future.

synthetic biology↗

bioRxiv2019

Rotational Dynamics Reduce Interference Between Sensory and Memory Representations

Sensory stimuli arrive in a continuous stream. By learning statistical regularities in the sequence of stimuli, the brain can predict future stimuli (Xu et al. 2012; Gavornik and Bear 2014; Maniscalco et al. 2018; J. Fiser and Aslin 2002). Such learning requires associating immediate sensory information with the memory of recently encountered stimuli (Ostojic and Fusi 2013; Kiyonaga et al. 2017). However, new sensory information can also interfere with short-term memories (Parthasarathy et al. 2017). How the brain prevents such interference is unknown. Here, we show that sensory representations rotate in neural space over time, to form an independent memory representation, thus reducing interference with future sensory inputs. We used an implicit learning paradigm in mice to study how statistical regularities in a sequence of stimuli are learned and represented in primary auditory cortex. Mice experienced both common sequences of stimuli (e.g. ABCD) and uncommon sequences (e.g. XYCD). Over four days of learning, the neural population representation of commonly associated stimuli (e.g. A and C) converged. This facilitated the prediction of upcoming stimuli, but also led unexpected sensory inputs to overwrite the sensory representation of previous stimuli (postdiction). Surprisingly, we found the memory of previous stimuli persisted in a second, orthogonal dimension. Unsupervised clustering of functional cell types revealed that the emergence of this second memory dimension is supported by two separate types of neurons; a stable population that maintained its selectivity throughout the sequence and a switching population that dynamically inverted its selectivity. This combination of sustained and dynamic representations produces a rotation of the encoding dimension in the neural population. This rotational dynamic may be a general principle, by which the cortex protects memories of prior events from interference by incoming stimuli.

neuroscience↗