Journal Article

Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition

Basu, Jayeeta, Zemelman, Boris V., Zaremba, Jeffrey D., Hitti, Frederick L., Losonczy, Attila, Cheung, Stephanie K., Siegelbaum, Steven A.

2016

Overview

In addition to providing well-characterized excitatory inputs, the entorhinal cortex also sends long-range inhibitory projections to the hippocampus. Basu et al. described this input in detail and characterized its role for learning and memory. Multimodal sensory stimuli activate long-range inhibitory input in vivo. This input enables precisely timed information transfer within the cortico-hippocampal circuit. In this way, long-range inhibitory projections play an important role in providing specificity of fear conditioning, and thus help prevent overgeneralization. Science , this issue p. 10.1126/science.aaa5694 Inhibitory inputs from the lateral entorhinal cortex help to make contextual memory associations specific. 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 mnemonic information to the immediate sensory input.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / CA1 Region, Hippocampal - physiology / CA3 Region, Hippocampal - physiology / Cognitive Development / Dendrites / Dendrites - physiology / Entorhinal Cortex - physiology / Evoked Potentials - physiology / Fear / GABAergic Neurons - physiology / gamma-Aminobutyric Acid - physiology / Information Transfer / Inhibition / Inhibitory Postsynaptic Potentials - physiology / Long Term Memory / Memory / Memory, Long-Term - physiology / Mice / Mnemonics / Neuronal Plasticity - physiology / Plasticity / Pyramidal Cells - physiology / RESEARCH ARTICLE SUMMARY / Stimuli / Storage / Synapses - physiology / Teaching Methods