Inhibitory top-down projections from zona incerta mediate neocortical memory.
Schroeder et al., Neuron (2023)
Apr 08, 2024
Abstract
Top-down projections convey a family of signals encoding previous experiences and current aims to the sensory neocortex, where they converge with external bottom-up information to enable perception and memory. Whereas top-down control has been attributed to excitatory pathways, the existence, connectivity, and information content of inhibitory top-down projections remain elusive. Here, we combine synaptic two-photon calcium imaging, circuit mapping, cortex-dependent learning, and chemogenetics in mice to identify GABAergic afferents from the subthalamic zona incerta as a major source of top-down input to the neocortex. Incertocortical transmission undergoes robust plasticity during learning that improves information transfer and mediates behavioral memory. Unlike excitatory pathways, incertocortical afferents form a disinhibitory circuit that encodes learned top-down relevance in a bidirectional manner where the rapid appearance of negative responses serves as the main driver of changes in stimulus representation. Our results therefore reveal the distinctive contribution of long-range (dis)inhibitory afferents to the computational flexibility of neocortical circuits.
Keywords: associative memory; circuit tracing; disinhibition; layer 1; long-range inhibition; neocortical circuits; plasticity; synaptic in vivo calcium imaging; top-down information; zona incerta.
Schroeder A, Pardi MB, Keijser J, Dalmay T, Groisman AI, Schuman E, Sprekeler H, Letzkus, JJ (2023). Inhibitory top-down projections from zona incerta mediate neocortical memory. Neuron 111:727-738.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.