COMMENTARY Is memory consolidation a multiple-circuit system? Federico Bermudez-Rattoni1 División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México 04510 D.F., Mexico ow is memory stored? This CREB (cAMP-response element binding memory consolidation if during this pro- important question has been protein) and protein synthesis inhibition cess an interaction between the hippo- H the focus of ample research in impaired spatial memory consolidation for campus and cortical regions occurs. the neurosciences. Memory, both tasks. It has been proposed that in the hip- from the neural point of view, is consid- pocampus the stimuli information remains ered a process by which the brain main- Molecular and System Consolidation for transitional periods, and for longer tains stable stimuli representations for The consolidation process implies impor- periods the information goes to the corti- a period and, depending on how long tant changes in brain function, and such cal regions (13). In this regard, simulta- a particular representation lasts, becomes changes can have different lengths of time. neous or sequential molecular changes a short-term memory (STM) or a long- Donald Hebb proposed that memory is at related to memory consolidation could be term memory (LTM) (1). At the beginning first in a labile state maintained by a re- occurring in different brain areas. A of the 20th century Muller and Pilzecker verberating neural ensemble and that number of studies have shown that func- proposed that new memories are fragile LTM arises from cellular changes in this tional integrity of the amygdala and the and consolidated over time, a theory that ensemble allowing memory stabilization cortex are important to consolidate and gave rise to the consolidation hypothesis (1, 2, 9). This theory stressed the weight maintain an implicit aversive taste memory (2). Fifty years later it was reported that an that cellular entities have in memory pro- trace for the long term. To demonstrate electroconvulsive shock applied after cessing, focusing research on the cellular a putative communication between the training disrupted memory and that events underlying memory (2, 9, 10). amygdala and the insular cortex involved memory disruption correlated with the in memory formation, the following ex- interval between training and electro- periments were done. First, behavioral convulsive shock application. As the elec- Areas outside the medial troconvulsive shock was longer spaced in enhancement of taste aversion memory time from training, memory impairment temporal lobe could be was induced by high-frequency electrical was reduced (2). Since then, several other or pharmacological stimulation of the researchers have shown that interfering participating in the amygdala, and then the observed memory treatments—from electroconvulsive shock facilitation was reversed by pharmacolog- to intracerebral microinjections of protein consolidation of ical manipulations in the cortex, suggest- synthesis inhibitors applied after acquisi- ing strong interaction of both structures tion—prevent LTM storage. Consistently, declarative memories. during memory consolidation (14, 15). LTM is not affected if the intrusive treat- Furthermore, it has been demonstrated ment is applied outside the vulnerability At the cellular level, STM undergoes ac- that simultaneous electrical recordings of time window. tivation of transduction cascades after the amygdala and cortex during taste fi Some of the recent advances in our neuronal stimulation. Thus, the STM aversion encoding showed a signi cant knowledge of the functional and morpho- remains as long as these cascades are ac- enhancement of functional connectivity logical changes related to experience have tive, but for LTM transduction signals are between the two structures (16). These been focused in one region of the limbic carried to the nucleus where transcription results suggest that both the amygdala and system in vertebrates: the hippocampus. factors are activated, which in turn leads to the insular cortex are important for con- Direct evidence came from clinical cases RNA translation into protein synthesis solidation and for maintaining the aversive like H.M., a patient in which surgical re- (11). These proteins account for cellular taste memory trace for the long term. moval of the majority of the medial tem- plastic changes that are considered the Accordingly, protein synthesis blockers poral lobe including the hippocampus led cellular correlations of stable LTM traces, applied in either the amygdala or the in- to profound memory consolidation deficits i.e., the cellular counterparts of consoli- sular cortex affect taste memory consoli- of declarative (explicit)* memory, such as dation. Hence, memory consolidation re- dation. Although it remains to be episodic memory, but not of non- quires protein synthesis. It has been demonstrated whether similar interaction declarative (implicit) memories, such as extensively reported that protein synthesis could be occurring among the hippocam- visual-motor skills (3, 4). Furthermore, inhibition disrupts LTM without affecting pus, ventral striatum, and cortical areas these observations have been experimen- STM; these cellular processes for memory during spatial memory consolidation; the tally reproduced in animal lesion studies consolidation have been called cellular results of Ferretti et al. (8) suggest that (5). In several papers it has been demon- consolidation. At the system level, i.e., different brain areas outside the medial strated that other structures in addition to where several brain structures are in- temporal lobe could be participating in the the hippocampus, such as the nucleus ac- volved, a multiple memory systems hy- consolidation of declarative memories. cumbens or some cortical regions, are in- pothesis has been proposed (see refs. 12 volved in episodic or recognition memory and 13). This hypothesis implies that dif- consolidation (6, 7). In PNAS, Ferretti ferent kinds of memories are organized in Author contributions: F.B.-R. wrote the paper. et al. (8) show that the ventral striatum independent brain systems. However, it is The author declares no conflict of interest. also has an important role in declarative also possible that LTM stability could See companion article 10.1073/pnas.0911757107. memory consolidation. In their paper, they be supported by the proliferation of mul- 1 were able to show in two differentially tiple memory circuits within the temporal E-mail: [email protected]. motivated spatial memory tasks (object in lobe and other brain regions. Thus, con- *Declarative or explicit memory is expressed through recol- lection of facts and events (times, space). Nondeclarative context and water maze task) that re- stant neural communication between memory is expressed through performance of motor duction of a transcriptional factor such as structures can be developed during skills (habits). www.pnas.org/cgi/doi/10.1073/pnas.1003434107 PNAS Early Edition | 1of2 Downloaded by guest on October 7, 2021 Remodeling of Neuronal Circuits by mals were submitted to response implicit dation could be to simultaneously analyze Experience cue learning (11). In other words, the axo- morphological changes in different brain The hypothesis that memory consolida- nal rearrangement was seen only when an- structures during and after memory con- tion could produce functional and mor- imals consolidated explicit but not implicit solidation. Although technically challeng- phological modifications of neuronal spatial memory components. Interestingly, ing, this would be the most appropriate way circuits has led to a great deal of experi- Ferretti et al. (8) further demonstrate that to truly understand the brain circuits in- mental studies. In this regard, it has been the ventral striatum is involved by means of volved in memory consolidation. The use of demonstrated that morphological rear- a protein synthesis blocker and transcrip- noninvasive brain-imaging methodologies rangements of dendrite spines and axonal tional factor antisense in the spatial mem- in human memory research has made great redistribution in the hippocampus and ory explicit but not implicit response of progress, such as the findings that areas cortex could occur after a variety of learning memory consolidation. Therefore, these outside the medial temporal lobe are also experiences (17). Accordingly, it has been findings show that some areas that are not involved in spatial memory (see refs. 18 and demonstrated that axonal rearrangements considered to be part of the medial tem- 19). The combination of those techniques in the mossy fibers of the hippocampus take poral lobe could also be significantly in- and brain experimental manipulation on place after several days of spatial water volved in spatial memory consolidation. lab animals will certainly shed light on our maze learning (11). However, these axonal Another possible strategy for finding those understanding of human memory and its rearrangements were not seen when ani- brain circuits involved in memory consoli- integration processes. 1. Dudai Y (2004) The neurobiology of consolidations, or, sis inhibitor in the nucleus accumbens shell. Neurobiol 14. Bermudez-Rattoni F (2004) Molecular mechanisms of how stable is the engram? Annu Rev Psychol 55:51–86. Learn Mem 92:45–52. taste-recognition memory. Nat Rev Neurosci 5:209–217. 2. McGaugh JL (2000) Memory: A century of consolida- 8. Ferretti V, et al. (2010) Ventral striatal