Dr. Jonathan Hakun
Psych 256 (002)
October 16, 2016
New Insight into the Mechanisms Involved with Memory Consolidation
Whenever an individual speaks of a memory contextually, the neurological mechanisms that’re responsible for carrying out such an action are largely implicated in the cortical connections previously established by hippocampal activity. This is all made possible due to the process of memory consolidation, which is defined as the process by which information that has entered the memory system becomes strengthened to such an extent where it is resistant to interference caused by trauma or other events (Goldstein, 2011). Such traumatic events, such as being concussed, sometimes result in a form of amnesia whereby the individual experiences a loss of memory for events that occurred prior to the traumatic event, known as retrograde amnesia. Based primarily in the graded property of retrograde amnesia (i.e., amnesia that is worse for experiences that occurred just before the brain injury), the standard model of consolidation was developed; this model, which precisely delineates how we are able to retrieve such vivid contextual memories, implies a complex and dynamic interplay between the hippocampus and various cortical regions, and has been widely accepted as the most accurate interpretation of the neurological mechanisms involved with consolidation, for the most part. Nevertheless, this model has left a great deal of ambiguity with regards to the possibility of other brain regions and similar neurological components being responsible for memory consolidation. To that end, a recent research study posted in the journal Science investigated a question aimed at furthering our understanding of the mechanisms involved with long-term memory consolidation, specifically with respect to the involvement of what’re known as Engram (memory) cells.
Before delving into the complexity of an Engram complex, it is primarily important to begin with an overview of the standard model of consolidation. According to this model, memory retrieval depends on the hippocampus during consolidation per se; however, once consolidation is complete, retrieval no longer depends on the hippocampus, and instead operates by means of intracortical connections. To expand upon this, this model explains consolidation as occurring through a sequence of three neurological events. The first step, involves the hippocampal coordination of memory information into their respective cortical regions. Because memories involve many different cognitive and sensory areas in the cortex, incoming information from a new experience is distributed across the respective cortical regions, which is coordinated via the hippocampus. The second step, which is the core feature of consolidation, is known as reactivation. In the reactivation stage, the hippocampus replays the neural activity associated with the given memory, which was previously established in the network connecting this structure and the aforementioned cortical regions. This activity results in the formation of connections between and within these cortical regions (as opposed to connections between the hippocampus and the cortex), which are subsequently strengthened upon each and every reactivation. The third and final step can be deemed the consolidation stage, whereby the cortical connections have been reactivated and subsequently strengthened to such an extent that the hippocampus is no longer needed to retrieve the given memory (Goldstein, 2011). The process of memory consolidation per se is made possible through a phenomenon known as long-term potentiation (LTP), which is the increased rate of neuronal firing that occurs due to prior activity at the synapse, resulting in structural changes and enhanced responding. The most noteworthy point of this model is the notion that the synaptic strength resulting from LTP and cellular consolidation is a pivotal aspect in the reactivation process, and hence the ability to store a memory. However, the likely possibility of other brain structures being involved in memory consolidation, names Engram cells, raises the question of whether or not these structures rely on the same mechanistic processes implicated in the standard model of consolidation.
According to Susumu Tonegawa and colleagues of the Massachusetts’s Institute of Technology’s Department of Brain and Cognitive Science, an Engram can be defined as the enduring physical and/or chemical changes underlying newly formed memory associations that’re elicited by learning (Tonegawa, Xu, Ramirez, & Redondo, 2015). Moreover, Engram cells are populations of neurons that’re activated by the process of learning, undergo enduring cellular changes as a consequence of learning, and whose reactivation occurs through part of the original stimuli delivered during learning resulting in memory recall (Tonegawa et al., 2015). But how exactly are these cells implicated in memory consolidation? A team of researchers at the Massachusetts’s Institute of Technology tried to answer just that; that is to say, they were interested in determining whether or not the mechanisms involved with standard model of memory consolidation are applicable to Engram cells, and to what extent.
Taking into consideration the structural changes that must occur in order for the formation of new memories to be made possible, the team of researchers used lab animals to stop this from occurring, thus inducing retrograde amnesia. By using injections of anisomycin, which is an antibiotic protein synthesis inhibitor, the team of researchers was successfully able to prevent these synaptic changes from occurring, thus hindering the ability for new memories to be formed (Ryan, Roy, Pignatelli, Arons, & Tonegawa, 2015). According to Bruce Goldstein, the key to the experimental usage of this antibiotic is when the injection occurs (chap. 7, pp 168-201), and the researchers state that this task was carried out “immediately after contextual fear conditioning” (Ryan et al., 2015). Prior to experimentation, the research team proposed that a specific pattern of connectivity of Engram cells is crucial for memory information storage and strengthened synapses in these cells would contribute to the overall memory retrieval process (Ryan et al., 2015). However, they found that the latter assertion was in fact false.
Based on their data, the researchers were shocked to find that increased synaptic strength resulting from cellular consolidation is not a crucial requisite from storing a memory (Ryan et al., 2015). Because the lab animals had been in a lab-induced state of retrograde amnesia, it was assumed that the ability for them to retrieve the memory associated with the initial contextual fear conditioning. However, when the team used a single-cell light-inducing experimental technique, the memory was in fact retrievable for the animals, indicating the mechanisms being independent of the synaptic firing rate involved with long-term potentiation (Ryan et al., 2015). These findings collectively illustrate the illusory nature of the neurological mechanisms involved with such complex cognitive processes such as memory. To that end, this research has opened the door for others to answer how exactly memory Engram cells operate with respect to memory consolidation.
Goldstein, E. B. (2011). Long-term memory: Encoding and retrieval. In L. Schreiber-Ganster (Ed.), Cognitive psychology: Connecting mind, research, and everyday experience (3rd ed., pp. 168-201). Belmont, CA: Wadsworth Cengage Learning Inc.
Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A., & Tonegawa, S. (2015). Engram cells retain memory under retrograde amnesia. Science, 348(6238), 1007-1013. DOI: 10.1126/science.aaa5542.
Tonegawa, S., Xu, L., Ramirez, S., & Redondo, R. (2015). Memory Engram cells have come of age. Neuron, 87(5), 918-31. DOI: http://dx.doi.org/10.1016/j.neuron.2015.08.00