Journal Article

Regulation of neuronal input transformations by tunable dendritic inhibition

Kaifosh, Patrick, Turi, Gergely F, Lovett-Barron, Matthew, Sternson, Scott M, Zemelman, Boris V, Bolze, Frédéric, Losonczy, Attila, Lee, Peter H, Sun, Xiao-Hua, Nicoud, Jean-François

2012

Overview

The authors use optical activation and cell type–specific pharmacogenetic silencing in vitro to show that dendritic inhibition critically regulates input-output transformations in mouse hippocampal CA1 pyramidal cells. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata. Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type–specific pharmacogenetic silencing in vitro , we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/378/1595/1554 / 631/378/1697/1691 / 631/378/548 / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biochemistry, Molecular Biology / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Biophysics / Cellular Biology / Cerebral Cortex - cytology / Channelrhodopsins / Dependovirus - genetics / DNA-Binding Proteins - genetics / Electric Stimulation / Excitatory Amino Acid Antagonists - pharmacology / GABA Antagonists - pharmacology / gamma-Aminobutyric Acid - pharmacology / Glutamate Decarboxylase - genetics / Glutamic Acid - pharmacology / Hippocampus (Brain) / In Vitro Techniques / Interneurons - cytology / Interneurons - physiology / Life Sciences / Ligand-Gated Ion Channels - genetics / Luminescent Proteins - genetics / Luminescent Proteins - metabolism / Membrane Potentials - drug effects / Membrane Potentials - genetics / Mice / Mice, Inbred C57BL / Mice, Transgenic / Models, Neurological / Mutation - genetics / Neural Inhibition - drug effects / Neural Inhibition - genetics / Neural Inhibition - physiology / Neurobiology / Neurons / Neurosciences / Parvalbumins - genetics / Patch-Clamp Techniques / Photic Stimulation / Physiological aspects / Pyramidal Cells - cytology / Pyramidal Cells - drug effects / Pyramidal Cells - physiology / Pyridazines - pharmacology / Receptors, Glycine - genetics / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Synapses - genetics / Synapses - physiology / Synaptic Transmission / Transcription Factors - genetics / Transduction, Genetic / Valine - analogs & derivatives / Valine - pharmacology