Abstract
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.
MeSH terms
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Animals
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Biophysics
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Cerebral Cortex / cytology
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Channelrhodopsins
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DNA-Binding Proteins / genetics
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Dependovirus / genetics
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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GABA Antagonists / pharmacology
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Glutamate Decarboxylase / genetics
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Glutamic Acid / pharmacology
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In Vitro Techniques
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Interneurons / cytology*
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Interneurons / physiology
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Ligand-Gated Ion Channels / genetics
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Models, Neurological
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Mutation / genetics
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Neural Inhibition / drug effects
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Neural Inhibition / genetics
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Neural Inhibition / physiology*
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Parvalbumins / genetics
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Patch-Clamp Techniques
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Photic Stimulation
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Pyramidal Cells / cytology
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Pyramidal Cells / drug effects
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Pyramidal Cells / physiology
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Pyridazines / pharmacology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Receptors, Glycine / genetics
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Synapses / genetics
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Synapses / physiology*
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Synaptic Transmission
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Transcription Factors / genetics
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Transduction, Genetic
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Valine / analogs & derivatives
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Valine / pharmacology
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gamma-Aminobutyric Acid / pharmacology
Substances
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Channelrhodopsins
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DNA-Binding Proteins
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Grhl3 protein, mouse
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Ligand-Gated Ion Channels
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Luminescent Proteins
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Parvalbumins
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Pyridazines
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RNA, Small Interfering
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Receptors, Glycine
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Transcription Factors
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Glutamic Acid
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gamma-Aminobutyric Acid
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2-amino-5-phosphopentanoic acid
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gabazine
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Glutamate Decarboxylase
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glutamate decarboxylase 2
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Valine