Schroeder, Anna;
Pardi, M Belén;
Keijser, Joram;
Dalmay, Tamas;
Groisman, Ayelén I;
Schuman, Erin M;
Sprekeler, Henning;
(2023)
Inhibitory top-down projections from zona incerta mediate neocortical memory.
Neuron
, 111
(5)
727-738.e8.
10.1016/j.neuron.2022.12.010.
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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.
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