Memory consolidation

Abstract

Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., "neural replay," which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation.

Figure 1.

Performance on the remote memory (childhood) portion of the autobiographical memory interview (Kopelman et al. 1989; three questions; maximum score = 9) by controls (CON), patients with circumscribed hippocampal (H) lesions, patients with large medial temporal lobe (MTL) lesions, and patients with medial temporal lobe lesions plus additional damage in the neocortex (MTL⁺). Brackets show standard error of the mean. Patients with damage limited to the MTL have the capacity to recall remote events, but this capacity is diminished when the damage extends into the neocortex.

Figure 2.

Animal studies revealing temporal gradients and other characteristics of cortical memory measured in a variety of different tasks. (A) Object discrimination learning in monkeys shows a temporal gradient over a period of 12 weeks (based on Zola-Morgan and Squire 1990). (B) Context fear conditioning sometimes shows a temporal gradient, but does not always do so. In a study in which a temporal gradient was observed in animals tested during pharmacological inhibition of the hippocampus (left panel), animals that successfully discriminated two testing contexts show a loss of memory with hippocampal inhibition, whereas animals that generalized do not (right panel based on Figs. 2 and 5 of Wiltgen et al. 2010). (C) Glucose uptake measured using radiolabeled 2-deoxyglucose shows a time-dependent increase in the cortex 25 days after radial-maze learning in mice (based on Bontempi et al. 1999). (D) Detection and shutdown of hippocampal sharp-wave ripples (SWR), a candidate mediator of consolidation, slows learning of a spatial radial-arm maze task (based on Girardeau et al. 2009). (E) Comparison of short and prolonged optogenetic (halorhodopsin)-induced inhibition of the hippocampus. There is an unexpected effect of brief hippocampal inhibition after 28 days in a training paradigm that shows a temporal gradient with more prolonged inhibition (based on Goshen et al. 2011). (F) Optogenetic activation of neurons in the retrosplenial cortex (RSC) labeled with channelrhodopsin via c-fos activation during context fear conditioning is sufficient to elicit a freezing response, bypassing the need for hippocampal binding during the early stage of systems consolidation. Even when the hippocampus (HPC) was inactivated by tetrodotoxin (TTX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), direct optogenetic activation of RSC elicited greater freezing 24 h after conditioning (middle) than during preconditioning (left). In the absence of optogenetic activation (right), hippocampal activity was essential to reactivate memory so soon after conditioning (based on Fig. 4E of Cowensage et al. 2014). MTL, medial temporal lobe.

Figure 3.

Hypothetical models of hippocampal–neocortical interactions during memory consolidation. (A) The standard model supposes that information is stored simultaneously in the hippocampus and in multiple cortical modules during learning and that, after learning, the hippocampal formation guides a process by which cortical modules are gradually bound together over time. This process is considered to be slow, occurring across weeks, months, or even longer (based on Frankland and Bontempi 2005). (B) In situations in which prior knowledge is available and, thus, cortical modules are already connected at the start of learning, a similar hippocampal–neocortical-binding process takes place. However, this process may involve the assimilation of new information into an existing “schema” rather than the slower process of creating intercortical connectivity (based on van Kesteren et al. 2012). HPC, hippocampus; mPFC, medial prefrontal cortex.