title: Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition.
abstract: The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored. We found that these long-range inhibitory projections enhance the specificity of contextual and object memory encoding. At the circuit level, these γ-aminobutyric acid (GABA)-releasing projections target hippocampal inhibitory neurons and thus act as a disinhibitory gate that transiently promotes the excitation of hippocampal CA1 pyramidal neurons by suppressing feedforward inhibition. This enhances the ability of CA1 pyramidal neurons to fire synaptically evoked dendritic spikes and to generate a temporally precise form of heterosynaptic plasticity. Long-range inhibition from entorhinal cortex may thus increase the precision of hippocampal-based long-term memory associations by assessing the salience of mnemonormation to the immediate sensory input.
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA. jayeeta.basu@nyumc.org sas8@columbia.edu.
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Basu
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zaremba
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Cheung
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Hitti
authors.affiliation: University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Zemelman
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Attila
authors.initials: A
authors.lastname: Losonczy
authors.affiliation: Department of Neuroscience, Kavli Brain Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA. jayeeta.basu@nyumc.org sas8@columbia.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Siegelbaum
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D018728:Entorhinal Cortex / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology; D059330:GABAergic Neurons / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005680:gamma-Aminobutyric Acid