Neuronal memory allocation

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Neuronal Memory Allocation refers to a category of brain processes that determine which neurons and synapses in a biological neural network encode a given memory trace.[1] There is an extensive body of literature that demonstrates that different types of information are primarily processed in different brain regions: for example, the hippocampus has a critical role in spatial information, the motor cortex and cerebellum process information concerning movements and motor commands, the amygdala has a critical role in handling emotional information, etc.[2] Once information reaches one of these brain regions, what memory allocation mechanisms determine which cells will be engaged to process and even store this information? Why are specific neurons and synapses within a brain circuit (and not others in the same circuit) recruited during a specific learning episode? Is the allocation of information to neurons and synapses within a circuit random, or are there mechanisms that control these processes? Recent findings demonstrate that memory allocation to specific neurons and synapses is not random. Instead, the transcription factor CREB has a critical role in regulating neuronal excitability mechanisms that determine which neurons are engaged in storing a given memory. Although in its infancy, studies of memory allocation in brain circuits promise to have a significant impact on revealing new memory mechanisms, and perhaps even on inspiring novel memory management algorithms for computer science.


Memory allocation in the context of neuroscience (the expression was first used in computer science) was first referred to in a review article by Jeijoon Won and Alcino J Silva.[3] This article reviewed findings that suggested that memory allocation is a competitive process, and that neurons with higher levels of CREB have an edge in this competition. The centerpiece of this review was an article by Alcino J Silva, Sheena Josselyn and their colleagues [4] where they showed that increasing the levels of CREB, in the mouse lateral amygdala with a viral vector, dramatically increased the probability that the neurons with the additional CREB would be involved in encoding a new emotional memory. Memory allocation is also related to synaptic tagging studies. Synaptic tagging refers to mechanisms that mark synapses for further modification or for continued maintenance.[5] These mechanisms can affect memory allocation because they can determine which synapses change during learning, so that related memories may be stored in nearby synapses in the same dendrite branch. Synaptic changes during learning are critical for memory.[6]

The Role of CREB in Allocation[edit]

The cAMP Responsive Element Binding protein (CREB) is a transcription factor that modulates the expression of genes involved in many biological processes including memory. The involvement of CREB in memory allocation was first demonstrated by increasing CREB levels in lateral amygdala neurons with a viral vector. The results suggested that higher CREB levels result in a ~3 fold increase in the probability these neurons encode an emotional memory.[4] The authors identified the neurons involved in memory by imaging the expression of immediate early genes that are activated during memory formation. In another pioneering study of the role of CREB in memory allocation, Sheena Josselyn and her colleagues trained mice and then deleted a relatively small number of neurons with artificial higher levels of CREB (expressed from a viral vector). Consistent with the idea that these neurons with higher CREB levels were preferentially chosen to encode the memory, deleting these neurons caused a profound amnesia. In contrast, deletion of the same small number of neurons, but with lower levels of CREB, did not affect memory. Presumably, most of these neurons with lower levels of CREB had not been chosen during learning to encode the memory, and therefore their deletion did not affect recall.[7] In a different study, neurons with higher CREB levels were not deleted, but instead they were temporarily inactivated. Remarkably, the authors of this study could weaken or even turn off a memory in the lateral amygdala simply by temporarily inactivating the neurons with higher CREB levels.[8]

Cellular Mechanism of Allocation[edit]

How does CREB affect memory allocation? It turns out that lateral amygdala neurons with higher levels of CREB are more excitable than other neurons with lower levels of CREB: they fired more action potentials and are more easily activated by synaptic stimulation.[8] This higher excitability could explain why they are preferentially chosen during memory formation. Indeed, synaptic studies of CREB neurons after training revealed higher synaptic potentiation (presumably caused by training) than neighboring neurons in the same brain structure (lateral amygdala). This provided direct evidence that the very mechanism thought to encode memory (synaptic potentiation), was more pronounced following training in neurons with higher CREB levels.[8]

Psychological Roles of Memory Allocation[edit]

Why is it that memory allocation is not random? What role could this mechanism have in cognitive function? Because of the enormous number and complexity of related memories stored in the brain, memory allocation is very likely to be an especially critical function in the brain. Without allocation mechanism that optimize storage by appropriately clustering and segregating different types of stored information, the brain would not be able to store and retrieve so many memories so efficiently. It is possible that the brain stores related information in overlapping networks of neurons, so that retrieval of one memory increases the probability of retrieval of other related memories. The retrieval of one memory often leads to the retrieval of a chain of other related memories: retrieval of one memory leads to the retrieval of another and so on. Memory allocation provides a molecular and cellular mechanism for this complex cognitive phenomenon

See also[edit]


  1. ^ Silva, A.J. et al.(2009). Molecular and Cellular Approaches to Memory Allocation in Neural Circuits. Science, Oct 16 2009;326(5951):391-5
  2. ^ Squire, L. R. (2004). "Memory systems of the brain: A brief history and current perspective." Neurobiology of Learning and Memory 82(3): 171-177
  3. ^ Won, J. and A.J. Silva, Molecular and cellular mechanisms of memory allocation in neuronetworks. Neurobiol Learn Mem, 2007
  4. ^ a b Han, J.H., S.A. Kushner, A.P. Yiu, C.J. Cole, A. Matynia, R.A. Brown, R.L. Neve, J.F. Guzowski, A.J. Silva, and S.A. Josselyn, Neuronal competition and selection during memory formation. Science, 2007. 316(5823): p. 457-60
  5. ^ Govindarajan, A., R. J. Kelleher, et al. (2006). "A clustered plasticity model of long-term memory engrams." Nat Rev Neurosci 7(7): 575-583
  6. ^ Lee, Y-S and Silva, AJ. The molecular and cellular biology of enhanced cognition Nat Rev Neurosci. 2009 Feb;10(2):126-40.
  7. ^ Han, J.-H., S. A. Kushner, et al. (2009). "Selective Erasure of a Fear Memory." Science 323(5920): 1492-1496
  8. ^ a b c Zhou, Y, Won J., Karlsson, M.G. Zhou, M., Rogerson, T, Balaji, J., Neve, R., Poirazi, P., Silva, A.J. CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nature Neuroscience, 2009. 12(11): p. 1438-43 Sep 27