Dynamics of Retrieval Strategies for Remote Memories

Abstract

Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.

Systems Reconsolidation Reveals a Selective Role for the Anterior Cingulate Cortex in Generalized Contextual Fear Memory Expression

“…Lesions or pharmacological inactivation of the hippocampus preferentially impact recently acquired contextual fear memory (Anagnostaras et al, 1999;de Oliveira Alvares et al, 2012;Goshen et al, 2011;Kitamura et al, 2009;Ward et al, 1999;Wiltgen et al, 2010;Winocur et al, 2009). Conversely, transient disruption of the anterior cingulate cortex (ACC) impairs the expression of remote, but not recent memory (Frankland et al, 2004;Goshen et al, 2011).…”

“…Conversely, transient disruption of the anterior cingulate cortex (ACC) impairs the expression of remote, but not recent memory (Frankland et al, 2004;Goshen et al, 2011). Such findings have led to the idea that the hippocampus serves a critical role in integrating information from a distributed cortical network representing various features of a memory, and that over time, the medial prefrontal cortex (including the ACC) gradually takes over this integrative role, allowing the memory to function independently of the hippocampus (Frankland and Bontempi, 2005).…”

P4‐253: Hilar GABAergic interneuron activity controls spatial learning and memory retrieval

“…There are many cases of patients with memory loss after medial temporal amnesia with no temporal gradient, and it has been shown that the hippocampus may not only be involved in encoding, but may also contribute to storage and retrieval of memory [33,34]. Recent animal studies also showed that hippocampal memory was not merely replaced by the cortical one, but rather both memories are in continuous interplay and there may indeed be a default role for the hippocampus in remote memory recall [33,35,36,37,38]. Intriguing recent studies have shown a default role for the hippocampus in remote memory recall [37,39], including a study where optogenetic inhibition of the CA1 pyramidal neurons in the hippocampus was sufficient to impair remote recall of memories using the contextual fear conditioning learning paradigm [38].…”

“…Recent animal studies also showed that hippocampal memory was not merely replaced by the cortical one, but rather both memories are in continuous interplay and there may indeed be a default role for the hippocampus in remote memory recall [33,35,36,37,38]. Intriguing recent studies have shown a default role for the hippocampus in remote memory recall [37,39], including a study where optogenetic inhibition of the CA1 pyramidal neurons in the hippocampus was sufficient to impair remote recall of memories using the contextual fear conditioning learning paradigm [38]. In agreement with these recent developments in the understanding of the role of the hippocampus in long term memory, we observed that precise, real-time inhibition of GABAergic interneuron activity in the hilus of the hippocampus, using optogenetic techniques, impairs memory retrieval up to 2 weeks after the initial memory formation, highlighting the importance of the hilar inhibitory interneurons in long-term memory retrieval.…”

Optogenetics in neuroscience: what we gain from studies in mammals

“…Goshen and colleagues demonstrated that photoinactivation of these neurons apparently inhibits both the acquisition and retrieval of remote fear memories while optogenetic reactivation of specific neuronal groups is sufficient to elicit a fear response [48] . On the other hand, optogenetics can be used to control epileptiform activity.…”