The hippocampus is coupled with the default network during memory retrieval but not during memory encoding

The brain's default mode network (DMN) is activated during internally-oriented tasks and shows strong coherence in spontaneous rest activity. Despite a surge of recent interest, the functional role of the DMN remains poorly understood. Interestingly, the DMN activates during retrieval of past events but deactivates during encoding of novel events into memory. One hypothesis is that these opposing effects reflect a difference between attentional orienting towards internal events, such as retrieved memories, vs. external events, such as to-be-encoded stimuli. Another hypothesis is that hippocampal regions are coupled with the DMN during retrieval but decoupled from the DMN during encoding. The present fMRI study investigated these two hypotheses by combining a resting-state coherence analysis with a task that measured the encoding and retrieval of both internally-generated and externally-presented events. Results revealed that the main DMN regions were activated during retrieval but deactivated during encoding. Counter to the internal orienting hypothesis, this pattern was not modulated by whether memory events were internal or external. Consistent with the hippocampal coupling hypothesis, the hippocampus behaved like other DMN regions during retrieval but not during encoding. Taken together, our findings clarify the relationship between the DMN and the neural correlates of memory retrieval and encoding.     

Systems-level reconsolidation: reengagement of the hippocampus with memory reactivation

Certain types of memories are dependent on the hippocampus for a short period of time following training, after which they are no longer susceptible to hippocampal manipulations. Having completed this initial consolidation process, a memory may once again engage the hippocampus (undergo reconsolidation) when recalled. Two studies in the current issue of Neuron make important advances in our understanding of reconsolidation but reach different conclusions about the modifiability of old memories.     

Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory

Relapse into drug taking among addicts often depends on learned associations between drug-paired cues and the rewarding effects of these drugs, such as cocaine (COC). Memory for drug-paired cues resists extinction and contributes to the high rate of relapse; however, the molecular mechanisms underlying these associations are not understood. We show that COC-conditioned place preference (CPP) activates ERK, CREB, Elk-1, and Fos in the nucleus accumbens core (AcbC) but not shell. Intra-AcbC infusions of U0126, an inhibitor of the ERK kinase MEK, prevent both the activation of ERK, CREB, Elk-1, and Fos and retrieval of COC-CPP. When tested again 24 hr or 14 days after intra-AcbC infusions of U0126 or another MEK inhibitor, PD98059, CPP retrieval and concomitant protein activation were significantly attenuated. Together, these findings indicate the necessity of the AcbC ERK signaling pathway for drug-paired contextual cue memories and suggest that these strong memories can become susceptible to disruption by therapeutic agents.     

The hippocampus and memory: insights from spatial processing

The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.     

The role of protein synthesis in memory reconsolidation in different time periods after fear conditioning in mice

We have studied the role of protein synthesis in reconsolidation of memory, activated by reminder at different time period after initial acquisition. Mice were trained in a single-trial fear conditioning task and then subjected to reminder, preceded by injection of protein synthesis inhibitor cycloheximide. It was found that this procedure impaired later memory retrieval if applied at 3, 6 and 24 h as well as 14 and 30 days after initial training. This data suggests that reactivated memory is followed by protein synthesis-dependent reconsolidation both at short (3-6 h) and long (14-30 days) intervals after initial acquisition.     

Neural basis for successful encoding and retrieval of prospective memory

Prospective memory (PM) refers to memory for future intentions. Difference due to memory (Dm effect) is the difference in neural activity related to stimuli that were subsequently remembered or forgotten. Using event-related potentials (ERPs), the present study investigated the Dm effect for PM using a subsequent task-switching paradigm. The results showed that a Dm effect of ERP P150 was more positive-going for later PM hit trials than for later PM forgotten trials during 100–200 ms. This Dm effect may reflect the process for the production of future intention or the process for attention. Consistent with previously reported Dm effects of other types of memory, we found that the fbN2 (250–280 ms) and late positivity component (400–700 ms) were stronger in later PM hit trials than in forgotten trials. The fbN2 was evoked by Chinese characters. The late positivity component was related to the precise encoding process. In conclusion, because of the early P150, PM encoding appears to be somewhat different from previously identified Dm effects. However, further research is needed. Our findings reveal that Dm effects of PM share similar characteristics with known Dm effects of other types of episodic memory after the very early stage of neural processing.     

The hippocampus, spatial memory and food hoarding: a puzzle revisited

Behavioural ecology assumes that cognitive traits and their underlying neural substrates are shaped by natural selection in much the same way as morphological traits are, resulting in adaptation to the natural environment of the species concerned. Recently, however, the 'neuroecology' approach of attempting to gain insight into brain structure and function by testing predictions about variation in brain structure based on knowledge of the lifestyle of the animal has been criticized on the grounds that such an adaptationist view cannot provide insight into the underlying mechanisms. Furthermore, the criticism has focussed on attempts to use variation in demand for spatial memory and in hippocampal size as a basis for predicting variation in cognitive abilities. Here, we revisit this critique against the field of so-called 'neuroecology' and argue that using knowledge of the natural history of animals has lead to a better understanding of the interspecific variation in spatial abilities and hippocampal size, and to the generation of novel hypotheses and predictions.     

Effects of protein synthesis inhibition during plant mitosis

The role of protein synthesis in onion root tips during mitosis has been studied, by using synchronous cell populations. Incubation in cycloheximide (CHM) or anisomycin during early or middle prophase induces the return of these cells to interphase. Therefore, it is suggested that essential proteins are synthesized, which determine the continuation of the cells in mitosis. In late prophase these treatments caused a certain delay in the entry into further stages, suggesting that a protein synthesis probably occurs which determines the duration of the transition from metaphase to anaphase. Mitotic processes which develop after metaphase do not seem morphologically dependent on protein synthesis, in spite of the fact that one of them, the nucleolar reconstruction, is markedly dependent on RNA synthesis. Unexpectedly this reorganization increases its rate in the absence of protein synthesis.     

Induction of amnesia evoked by memory reconsolidation disruption with glutamate or serotonin receptor antagonists depends on protein synthesis activation

Effects of DNQX (ionotropic AMPA/cainate glutamate receptor antagonist) and metiotepin (serotonin receptor antagonist) and cycloheximide (protein synthesis inhibitor) on long-term memory reconsolidation processes were studied in snail Helix lucorum with definite type of food aversion conditioned reflex. DNQX or cycloheximide injected immediately before reminding disrupt retrieval of the food aversion 24 hours after conditioning, and repeated trials of learning with the same food as at initial trials did not form the food aversion 2 weeks later. Metiotepin + reminding also discrupt recalling of food aversion 24 hours after conditioning, while food aversion was repaired after repeated trials 2 weeks later. Simultaneous injections of DNQX + cycloheximide or metiotepin + cycloheximide immediately before reminding do not discrupt the food aversion. We suggest that unrecovered and recovered forms of amnesia induced by AMPA/cainate glutamate receptor antagonists or serotonin receptor antagonist, respectively, need specific protein molecules de novo.     

The mechanisms of memory reorganization during the retrieval of acquired behavioral experience in chicks: the effects of protein synthesis blockade in the brain]

It is currently assumed that disruption of memory formation by inhibitors of protein synthesis can occur in a relatively short time interval before and after training. However, there is some evidence that memory may be disrupted by delayed injections of protein synthesis inhibitors during "reminder" treatment, i.e., environmental cue that was presented earlier during the training procedure. Our experiments were conducted to test the late effects of protein synthesis inhibitor cycloheximide on memory in chicks using a reminder treatment. A standard passive avoidance task was presented to day-old chicks. A reminder (a dry bead of the same color as during training) was delivered within 2, 24, or 48 hours after the training. Chicks were bilaterally intracranially injected with cycloheximide (20 micrograms) into the IMHV area 5 min prior to reminder administration. Testing was conducted 0.5, 1, 3, 24, and 48 hours after the reminder. Administration of cycloheximide before the reminder resulted in transient amnesia. Duration of amnesia decreased with increasing interval between the training and reminder procedures. These results suggest that memory reactivated by the reminder treatment is subjected to reorganization and reconsolidation depending on protein synthesis. The gradual decrease in vulnerability of memory to protein synthesis inhibitor points to development of memory consolidation process in the interval between 2 and 48 h after training.