Dendritic mechanisms of memory encoding in the hippocampus

Abstract

The mammalian brain learns and forms memories continuously throughout an individual’s lifetime, with an astonishing capacity to acquire, retain, and retrieve relevant new information while simultaneously filtering and forgetting behaviorally irrelevant experiences. Memories are thought to be encoded during ‘online’ periods of awake exploration and subsequently consolidated into stable memories during ‘offline’ periods of sleep; otherwise, memories are forgotten. Both the rapid encoding of spatial and episodic memories and their subsequent consolidation rely critically on the CA1 region of the hippocampus. Pyramidal neurons in CA1 rapidly form spatially selective firing fields called place fields, which serve as the cellular basis for memory encoding. The primary neural basis for these memory processes is thought to be synaptic plasticity, which underlies changes in the functional connectivity of neuronal circuits in the brain. Various forms of experience-dependent synaptic modifications, particularly at excitatory glutamatergic synapses, are widely considered to be the primary substrates of memory encoding and consolidation. However, causal links have yet to be made in vivo between synaptic plasticity and memory formation due to the difficulty of monitoring and manipulating plasticity at the single-neuron resolution in awake behaving animals. To address this, we combined high-resolution in vivo single-cell labeling (Chapter 1), 3D real-time motion correction (Chapter 2), and multicompartment two-photon dendritic glutamate, calcium, and voltage imaging to examine the subcellular plasticity mechanisms supporting hippocampal-dependent memory formation (Chapter 3)