Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Memory Allocation in Neural Circuits


Science 16 October 2009: Vol. 326. no. 5951, pp. 391 - 395

Molecular and Cellular Approaches to Memory Allocation in Neural Circuits

Alcino J. Silva, Yu Zhou, Thomas Rogerson, Justin Shobe, J. Balaji

Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Psychology and the Brain Research Institute, University of California, Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095–1761, USA.


Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention. Recent findings suggest that memory allocation is not random, but rather specific mechanisms regulate where information is stored within a neural circuit. New methods that allow tagging, imaging, activation, and inactivation of neurons in behaving animals promise to revolutionize studies of brain circuits, including memory allocation.

Memory allocation refers to a set of processes that determine where information is specifically stored in a neural circuit. Does memory allocation involve competition between different cells (or synapses) activated during learning? Do memory allocation processes take place at different time scales? The allocation of information is an especially important problem for the brain because of the enormous number of related memories stored throughout a lifetime.

The cyclic adenosine monophosphate (cAMP) responsive element–binding protein (CREB) regulates the transcription of other genes and has a well-known role in the stability of synaptic potentiation and memory. Recent studies provide compelling evidence that there are molecular and cellular processes that determine which cells are recruited to store information within a neural circuit. Research studies suggested that CREB activated during learning triggers changes in the cell (such as an increase in excitability) that then affect whether that cell participates in subsequent memories. This idea was tested by artificially increasing the levels of CREB in amygdala neurons, using a replication-defective herpes viral vector. The initial results showed that higher CREB levels increase the probability (~threefold) that amygdala neurons participate in memory for tone fear conditioning.

CREB cells fire more action potentials and are activated more easily than neighbor cells. Because CREB cells are more excitable than other cells, they are also more likely to respond to sensory inputs and therefore be activated during conditioning. Previous studies have suggested that learning triggers a temporary increase in neuronal excitability. This excitability increase could define a window of time in which related memories are co-stored in overlapping populations of neurons.

Recent computational modeling studies have suggested that neurogenesis has a role in memory allocation. When the excitability and plasticity of a specific set of new neurons is high, they are very likely to participate in the encoding of incoming memories. A newer cluster of memories would be integrated into another group of maturing neurons. This process continues, with each subsequent set of newly born dentate neurons incorporating a newer set of memories, each set with a distinct time stamp. Thus, new neurons with high excitability and plasticity could endow the dentate gyrus with pattern integration abilities.

Single neurons are likely to be involved in multiple memories. As predicted by clustered-plasticity models, long-term potentiation at a specific synapse in a CA1 pyramidal neuron increases the probability for potentiation at neighboring synapses. This affects synapses within 10 µm of the potentiated synapse, and the effect may last at least 10 min. Events closely associated in time (within 10 min of each other) are likely to be allocated (i.e., trigger synaptic modifications) to neighboring synapses in recruited CA1 neurons. Memories with both overlapping cellular and synaptic domains would be expected to be more interconnected (more often co-retrieved) than memories that only share similar cell populations.

Episodic memories usually involve extended temporal interconnections between complex stimuli. Memory allocation mechanisms could potentially be used to set up partially overlapping populations of neurons that could account for these extended temporal interconnections.

Newly developed strategies for imaging, activating, and inactivating specific neurons in a given brain region are changing the way neuroscientists tackle traditional problems, and more importantly, they are opening up new areas of investigation, such as memory allocation. Mechanisms working at different time scales (including CREB signaling, neurogenesis, and synaptic selection) modulate the allocation of memory to specific cells and synapses within a neural network. Memory allocation will probably involve a plethora of synaptic, cellular, and systems mechanisms regulated by a myriad of molecular processes, including CREB.

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