Molecular Basis of Memory, Volume - 1st Edition
Researchers have developed a way to pinpoint the molecules involved in forming a specific memory. The finding, in genetically engineered mice, gives scientists new insight into how memories are formed.
For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins. The tag allows synapses to capture newly made proteins and thus solidify a memory. But the molecular details of the process have been a mystery. They genetically engineered a strain of mice to make AMPARs that could be traced by their green glow.
The transgenic mice were taught to associate a specific environment with a foot shock, a process known as fear conditioning. After fear conditioning had triggered new AMPARs deep in the neuron's nucleus, the researchers tracked where the newly made proteins went. In the February 22, , issue of the journal Science , the researchers reported that the newly synthesized AMPARs travel to and become captured by only certain hippocampus synapses—presumably the ones holding the new memory—within hours.
The more we learn about memory, the weirder it gets
Synaptic connections are made onto small nubs on the neuron called spines. These spines come in 3 different shapes called thin, stubby and mushroom. The mushroom spines also figured prominently in the same neurons when fear conditioning was reversed by repeatedly exposing the animals to the feared situation without getting shocked—a procedure called extinction learning.
In this proposal, we outline a series of genetic, pharmacological, biochemical and molecular experiments to examine the role that PKA plays in hippocampal function.
In Specific Aim 1, we will use pharmacological and biochemical approaches to define the role that PKA plays in memory consolidation. Our initial characterization of the R AB transgenic animals has revealed deficits in contextual fear conditioning and spatial memory after massed training. In Specific Aim 2, we will determine if memory deficits in the R AB transgenic mice can be overcome by increasing the number of training trials or altering the training schedule.
The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB
Specific Aim 3 will determine if PKA plays a general role in hippocampal function by examining the performance of R AB transgenic mice in non-spatial tests of hippocampal function using tasks such as social transmission of food preferences and object recognition. The critical molecular targets of PKA and the identity of genes whose expression is regulated by this signal transduction pathway during memory storage remain crucial open questions, and these studies are the focus of Specific Aim 4.
With the combination of genetic, molecular and pharmacological studies outlined in this grant proposal, we hope to determine the molecular basis of long-term memory storage and define the role that PKA plays in synaptic plasticity and long-term memory. Toggle navigation. Recent in Grantomics:.
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Name University of Pennsylvania. Related projects. J Clin Invest