It has been proposed that short-term memory is encoded by ongoing activity of neuronal networks within the prefrontal and parietal regions of the neocortex, however the precise mechanism of storage remains controversial. Due to the importance of short-term memory in human cognitive function and its decline with age and neurological disorders, the identification of the neural basis of short-term memory has been a subject of significant research efforts. Two hypotheses have been proposed for short-term memory storage in the cerebral cortex, persistent neural activity and sequential neural activity. In order to discriminate between these two hypotheses, I will study the neural dynamics in the rat prefrontal and parietal cortices during short-term memory. Rats offer a number of distinct advantages for the measurement of cortical dynamics that underlie short-term memory. First, rats can be trained in cognitive tasks that involve short-term memory. Second, rats are amenable to advanced techniques for the measurement of neural activity, such as in vivo two-photon microscopy of genetically encoded calcium sensors (in vivo imaging). In vivo imaging enables the recording of many neurons simultaneously, which is crucial to discriminate between persistent neural activity and sequential neural activity. My experimental approach is divided into 3 aims. First I aim to optimize and characterize a novel system that I developed for in vivo imaging during voluntary head restraint. This approach allows for rats trained in short-term memory tasks to temporarily head restrain themselves to while cortical dynamics are recorded.
In Aim 2 I will use this technique to record activity in the rat frontal cortex during a memory guided orienting task.
In Aim 3 I record neural activity in the rat parietal cortex under the same conditions. Both persistent activity and sequential activity have been predicted in frontoparietal circuits during memory guided movement tasks. Recording in two regions during this task should allow me to critically evaluate the relationship between these two proposed forms of cortical dynamics and short-term memory.
The goal of the research I will propose for my postdoctoral training is to study the neurobiology of short-term memory in the laboratory rat, and to identify the neural dynamics that encode short-term memory. Short-term memory is crucial to many of the complex behaviors of humans and other animals, however, little is known about where in the brain such memories are stored, why the capacity for short-term memories decline with age and how we might design therapies for memory disorders. Understanding the neurobiological basis of short-term memory formation will be crucial to develop therapies that protect, restore or enhance this cognitive ability.