Garren, J. | Search bioRxiv

bioRxiv2025

Newly trained navigation and verbal memory skills elicit changes in task-related networks but not brain structure

Training cognitive skills, such as remembering a list of words or navigating a new city, has important implications for everyday life. Yet, understanding what brain changes underlie the acquisition of complex cognitive skills remains unresolved. Here, we developed and validated intensive multiweek interventions in which participants were randomly assigned training in either navigation or verbal memory. Healthy young participants (N=75) underwent structural and functional imaging prior to and following the training. Based on pre-registered and exploratory analyses, we did not find any evidence for changes to gross hippocampal or hippocampal subfield volume, cortical brain volume, or white matter connectivity due to the training. In contrast, network-based analyses suggested changes in task-related informational connectivity, which occurred primarily between cortical areas and mostly involved putative cognitive control networks. These results suggest that cognitive interventions target more transient configurations in network connectivity rather than more durable structural changes.

neuroscience↗

bioRxiv2023

GLUT4 dynamic subcellular localization is controlled by AMP kinase activation as revealed by proximal proteome mapping in human muscle cells

Regulation of glucose transport into muscle and adipocytes, central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter in the plasma membrane (PM). Physiologic signals (activated insulin receptor or AMP kinase [AMPK]), acutely increase PM GLUT4 to enhance glucose uptake. Here we show in kinetic studies that intracellular GLUT4 is in equilibrium with the PM in unstimulated cultured human skeletal muscle cells, and that AMPK promotes GLUT4 redistribution to the PM by regulating both exocytosis and endocytosis. AMPK-stimulation of exocytosis requires Rab10 and Rab GTPase activating protein TBC1D4, requirements shared with insulin control of GLUT4 in adipocytes. Using APEX2 proximity mapping, we identify, at high-density and high-resolution, the GLUT4 proximal proteome, revealing GLUT4 traverses both PM proximal and distal compartments in unstimulated muscle cells. These data support intracellular retention of GLUT4 in unstimulated muscle cells by a dynamic mechanism dependent on the rates of internalization and recycling. AMPK promoted GLUT4 translocation to the PM involves redistribution of GLUT4 among the same compartments traversed in unstimulated cells, with a significant redistribution of GLUT4 from the PM distal Trans Golgi Network Golgi compartments. The comprehensive proximal protein mapping provides an integrated, whole cell accounting of GLUT4s localization at a resolution of [~]20 nm, a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in physiologically relevant cell type and as such, sheds new light on novel key pathways and molecular components as potential therapeutic approaches to modulate muscle glucose uptake.

cell biology↗