Control of neocortical memory by long-range inhibition in layer 1

Abstract

Mounting evidence identifies layer 1 (L1) as a central site of memory in sensory neocortex. While this work revealed plasticity in several excitatory brain-wide afferent systems, the existence, connectivity and memory-related signaling of long-range inhibitory input to L1 remains elusive. We report that inhibitory afferents from zona incerta project specifically to auditory cortex L1, where they connect selectively to interneurons to disinhibit the cortical circuit and facilitate behavioral memory. Chronic calcium imaging of these synapses identifies a balanced form of plasticity that develops rapidly during threat learning and is characterized by the de novo appearance of negative stimulus responses which transmit most information. Our results therefore pinpoint malleability of long-range (dis)inhibitory afferents to L1 as a key factor for the exquisite computational flexibility of this unique layer.

Layer 1 of somatosensory cortex: An important site for input to a tiny cortical compartment

“…Neocortical layer 1, long an enigma (Burkhalter 1989; Gămănuţ et al 2018; Hubel 1982; Ibrahim et al 2020; Marín-Padilla 1998), has recently become central to ideas about consciousness and perception (Aru et al 2020; Gidon et al 2020; Guest et al 2021; Ibrahim et al 2021; M. Larkum 2013; Schroeder et al 2022; Suzuki and Larkum 2020; Takahashi et al 2016; Takahashi et al 2020). These ideas seem astonishing for such a cell sparse, tiny layer, located at the surface of cortex, spanning only 100 microns in width, and containing only GABAergic interneurons (Rudy et al 2011; Schuman et al 2021).…”