Layer-specific control of inhibition by NDNF interneurons

• 成果类型: Article
• 署名作者: Naumann, Laura Bella; Hertaeg, Loreen; Mueller, Jennifer; Letzkus, Johannes J.; Sprekeler, Henning
• 署名单位: Institute of Science & Technology - Austria; Technical University of Berlin; University of Freiburg; University of Freiburg; University of Freiburg; University of Freiburg; University of Freiburg
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10383
• DOI: 10.1073/pnas.2408966122
• 发表日期: 2025-01-28
• 关键词: visual-cortex; modulation; circuits; neurotransmitter; prediction; neocortex; feedback; neurons; shapes

摘要

Neuronal processing of external sensory input is shaped by internally generated top- down information. In the neocortex, top-down projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and the dendrites of pyramidal cells. Here, we investigate the hypothesis that NDNF interneurons shape cortical computations in an unconventional, layer-specific way, by exerting presynaptic inhibition on synapses in layer 1 while leaving synapses in deeper layers unaffected. We first confirm experimentally that in the auditory cortex, synapses from somatostatin-expressing (SOM) onto NDNF neurons are indeed modulated by ambient Gamma-aminobutyric acid (GABA). Shifting to a computational model, we then show that this mechanism introduces a distinct mutual inhibition motif between NDNF interneurons and the synaptic outputs of SOM interneurons. This motif can control inhibition in a layer-specific way and introduces competition between NDNF and SOM interneurons for dendritic inhibition onto pyramidal cells on different timescales. NDNF interneurons can thereby control cortical information flow by redistributing dendritic inhibition from fast to slow timescales and by gating different sources of dendritic inhibition.