Parallel processing by cortical inhibition enables context-dependent behavior

• Published in: Nature neuroscience Vol. 20; no. 1; pp. 62 - 71
• Main Authors: Kuchibhotla, Kishore V, Gill, Jonathan V, Lindsay, Grace W, Papadoyannis, Eleni S, Field, Rachel E, Sten, Tom A Hindmarsh, Miller, Kenneth D, Froemke, Robert C
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2017; Nature Publishing Group
• Subjects: 59; 59/5; 631/378/2619; 631/378/3917; 64; 64/60; 9/10; 9/74; Acoustics; Analysis; Animal Genetics and Genomics; Animals; Auditory Cortex - physiology; Auditory Perception - physiology; Bats; Behavior; Behavior, Animal - physiology; Behavioral Sciences; Biological Techniques; Biomedicine; Cholinergic mechanisms; Interneurons; Mice, Transgenic; Neural Inhibition - physiology; Neurobiology; Neurons - physiology; Neurosciences; Sensory stimulation; Somatostatin - metabolism; Vasoactive Intestinal Peptide - metabolism; Visual Cortex - physiology; New York; United States > US
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/nn.4436

Animals have a remarkable ability to adjust their behavioral response to the same stimulus based on the immediate behavioral context. The authors show that the nucleus basalis broadcasts a contextual signal to the auditory cortex that is then translated by inhibitory networks to regulate excitatory neuronal output and behavior. Physical features of sensory stimuli are fixed, but sensory perception is context dependent. The precise mechanisms that govern contextual modulation remain unknown. Here, we trained mice to switch between two contexts: passively listening to pure tones and performing a recognition task for the same stimuli. Two-photon imaging showed that many excitatory neurons in auditory cortex were suppressed during behavior, while some cells became more active. Whole-cell recordings showed that excitatory inputs were affected only modestly by context, but inhibition was more sensitive, with PV + , SOM + , and VIP + interneurons balancing inhibition and disinhibition within the network. Cholinergic modulation was involved in context switching, with cholinergic axons increasing activity during behavior and directly depolarizing inhibitory cells. Network modeling captured these findings, but only when modulation coincidently drove all three interneuron subtypes, ruling out either inhibition or disinhibition alone as sole mechanism for active engagement. Parallel processing of cholinergic modulation by cortical interneurons therefore enables context-dependent behavior.