Short-term memory, the ability to hold information in mind over short timescales, is a fundamental cognitive process underlying an array of complex abilities. In contrast to long-term memory, which involves modification of synaptic connections, short-term memory is associated with sustained neural activity in cortical and subcortical structures. In particular, recent studies have suggested that the posterior parietal cortex plays a key role in maintaining mnemonic traces. However, it is not understood how the neural activity in these regions supports the maintenance of short-term memory. The goal of this project is to develop a short-term memory task for head-fixed mice and to leverage recent advances in 2-photon calcium imaging and optogenetics to dissect the neural circuits underlying short-term memory. This goal will be undertaken with the following aims:
(Aim 1) Develop a short-term memory task for mice, and measure the neural signature of short-term memory in visual and parietal cortices using 2-photon calcium imaging.
(Aim 2) Determine the necessity and time course of sustained activity in specific cortical regions using targeted optogenetic inactivation.
(Aim 3 a) Investigate the role of norepinephrine on sustained cortical activity during the short-term memory task by optogenetic modulation of noradrenergic tone.
(Aim 3 b) Determine whether the duration and accuracy of short-term memory maintenance can be improved by optogenetic modulation of norepinephrine release. Developing a systems-level understanding of short-term memory will yield critical insights into how the brain represents and maintains information, and may have translational implications for treating deficits in short-term memory commonly observed in normal aging and psychiatric disorders.

Public Health Relevance

Deficits in short-term memory, the ability to hold information in mind over short timescales, have been described in normal aging and in several psychiatric disorders. In this project, we hope to establish a basic scientific understanding of how neural activity in visual and parietal cortex maintains short-term memory. We will also establish a system by which we can test the role of specific neuromodulators on short-term memory using optogenetic manipulations, thereby generating therapeutic targets for treating deficits in short-term memory.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Career Transition Award (K99)
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Special Emphasis Panel (ZMH1)
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Desmond, Nancy L
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Massachusetts Institute of Technology
Internal Medicine/Medicine
Schools of Arts and Sciences
United States
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Goard, Michael J; Pho, Gerald N; Woodson, Jonathan et al. (2016) Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions. Elife 5: