Spatiotemporal refinement of signal flow through association cortex during learning

Abstract

Association areas in neocortex encode novel stimulus-outcome relationships, but the principles of their engagement during task learning remain elusive. Using chronic wide-field calcium imaging, we reveal two phases of spatiotemporal refinement of layer 2/3 cortical activity in mice learning whisker-based texture discrimination in the dark. Even before mice reach learning threshold, association cortex-including rostro-lateral (RL), posteromedial (PM), and retrosplenial dorsal (RD) areas-is generally suppressed early during trials (between auditory start cue and whisker-texture touch). As learning proceeds, a spatiotemporal activation sequence builds up, spreading from auditory areas to RL immediately before texture touch (whereas PM and RD remain suppressed) and continuing into barrel cortex, which eventually efficiently discriminates between textures. Additional correlation analysis substantiates this diverging learning-related refinement within association cortex.Our results indicate that a pre-learning phase of general suppression in association cortex precedes a learning-related phase of task-specific signal flow enhancement.

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

“…More recently, the advent of genetically encoded calcium 1 and voltage indicators 2,3 , along with transgenic approaches for broadly expressing these indicators in the brain in a cell-type specific fashion 4,5 has enabled mesoscale imaging of multiple cortical regions simultaneously [6][7][8] . These studies have revealed how neural activity across multiple regions of the cortex are coordinated in a variety of brain states and behaviors [9][10][11][12][13][14][15] .…”

Sources of widefield fluorescence from the brain

“…The concentrating effect of scattering is lost when angles at the brain surface are randomized, such as by overlying skull. In mouse, widefield imaging is often performed through intact skull ( Mohajerani et al, 2013 ; Silasi et al, 2016 ; Allen et al, 2017 ; Makino et al, 2017 ; Gilad and Helmchen, 2020 ; Valley et al, 2020 ). Mouse skull is ~150–300 µm thick and transparent but strongly scattering ( Soleimanzad et al, 2017 ; Wang et al, 2018 ).…”

Learning-related population dynamics in the auditory thalamus

“…forelimb movement, nose twitching, whisking, licking etc. ), which were recently found to have substantial impact on neuronal activity in different brain areas ( Gilad et al, 2018 ; Gilad and Helmchen, 2020 ; Musall et al, 2019 ; Stringer et al, 2019 ). As mentioned above, we continuously monitored the body movements of the mouse throughout the experiment ( Figures 1A and 5A ).…”

“…Learning, the process of acquiring new knowledge through experience, is known to involve disparate brain areas, and particularly the cortex. For example, learning to discriminate between different sensory stimuli leads to changes in the respective primary sensory areas ( Blake et al, 2002 ; Chen et al, 2015 ; Driscoll et al, 2017 ; Gilad and Helmchen, 2020 ; Jurjut et al, 2017 ; Komiyama et al, 2010 ; Li et al, 2008 ; Makino and Komiyama, 2015 ; Poort et al, 2015 ; Yan et al, 2014 ). Cortical neural responses have often been shown to strengthen after learning.…”

“…Cortical neural responses have often been shown to strengthen after learning. For example, neural signals in animals that gain expertise in a specific task, show increased activity and result in higher discriminatory power between the learned stimuli ( Gilad et al, 2018 ; Gilad and Helmchen, 2020 ; Poort et al, 2015 ; Wiest et al, 2010 ; Yan et al, 2014 ). In other cases, decreased responsiveness to the learned stimuli have been measured.…”