Working Memory DLPFC Knowing Neurons Don Davies

Have you ever asked for a phone number only to forget it moments later?  The only way to remember it is to rehearse the digits over and over in your head.  This is an example of working memory, which is a type of short-term memory for storage and manipulation of information necessary for higher order cognition.  Working memory is impaired in some diseases such as schizophrenia and Alzheimer’s.  Since working memory is used for daily tasks, memory impairment often is associated with a reduced quality of life.  If scientists can understand how the brain circuitry creates working memory, scientists may be able to treat the cognitive symptoms of diseases that impair working memory.

DLPFC Dorsolateral Prefrontal Cortex Neuroscience Knowing Neurons BrainIt has been known for quite some time that damage in a sub-region of the prefrontal cortex termed the dorsolateral prefrontal cortex (DLPFC) impairs working memory.  However, until recently, the DLPFC circuitry has not been explored in great detail.  One essential component to this circuitry is NMDA receptors, which are responsible for proper information signaling between neurons.  NMDA receptors are activated by the neurotransmitter glutamate, which binds to the NMDA receptor, facilitating information signaling between the neurons.  A disturbance in NMDA receptors in the DLPFC may contribute to such brain diseases as schizophrenia and Alzheimer’s (for review see Paoletti, Bellone, and Zhou, 2013). Postmortem studies of brains from humans with schizophrenia show structural abnormalities in the DLPFC related to NMDA receptors (Hashimoto et al., 2008).  Similarly, Alzheimer’s neurons have a reduction in the amount of NMDA receptors (Snyder et al., 2005).  These studies open the door to the investigation of NMDA receptor levels in patients with schizophrenia and Alzheimer’s disease.  Unfortunately, conducting studies on humans is logistically challenging, so animal models are a good alternative to answering these complex questions.

Experimental Design NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex Knowing NeuronsA recent study using primates, an animal model similar to humans, demonstrated that NMDA receptors are involved with working memory (Wang et al., 2013).  In this study, electrical recordings from the DLPFC of primates (monkeys) were obtained while they were engaged in a working memory task.  This task (displayed in the figure to the left) consisted of presenting the monkey with a blank screen that only had a fixation cross, then displaying a circle on a screen in one of eight possible locations.  The circle was then removed, and the monkey was required to hold the position of the circle in memory for 2.5 seconds.  After this delay phase, the monkey indicated where the circle was previously located.

Under normal conditions, the monkey’s DLPFC neurons fired rapidly when holding the circle in their memory during the delay phase.  Administration of a drug that blocks NMDA receptors reduced this firing rate in the DLPFC neurons during the delay phase.  These results suggest that NMDA receptors in the DLPFC are important while engaged with a working memory task!  These results may aid in the development of novel drug therapies that focus on changing the firing rate of neurons with NMDA receptors in the DLPFC, which may treat the working memory impairments found in people with schizophrenia and Alzheimer’s.

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Written by Don A. Davies

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References:

Hashimoto T., Arion D., Unger T., Maldonado-Avilés J.G., Morris H.M., Volk D.W., Mirnics K. & Lewis D.A. (2007). Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia, Molecular Psychiatry, 13 (2) 147-161. DOI: 

Paoletti P., Bellone C. & Zhou Q. (2013). NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease, Nature Reviews Neuroscience, 14 (6) 383-400. DOI:

Snyder E.M., Nong Y., Almeida C.G., Paul S., Moran T., Choi E.Y., Nairn A.C., Salter M.W., Lombroso P.J., Gouras G.K. & Greengard P. (2005). Regulation of NMDA receptor trafficking by amyloid-β,Nature Neuroscience, 8 (8) 1051-1058. DOI: 

Wang M., Yang Y., Wang C.J., Gamo N., Jin L., Mazer J., Morrison J., Wang X.J. & Arnsten A.T. (2013). NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex, Neuron, 77 (4) 736-749. DOI: 

Images adapted from Wang et al., 2013 and Corbis, and made by Don A. Davies and Kate Jones

knowingneurons

Knowing Neurons is an award-winning neuroscience education and outreach website that was created by young neuroscientists. The global team members at Knowing Neurons explain complicated ideas about the brain and mind clearly and accurately using powerful images, infographics, and animations to enhance written content. With an extensive social media presence, Knowing Neurons has become an important science communication outlet and resource for both students and teachers.

knowingneurons

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Knowing Neurons is an award-winning neuroscience education and outreach website that was created by young neuroscientists. The global team members at Knowing Neurons explain complicated ideas about the brain and mind clearly and accurately using powerful images, infographics, and animations to enhance written content. With an extensive social media presence, Knowing Neurons has become an important science communication outlet and resource for both students and teachers.

5 Comments

  1. In our psychology class we are learning about the short-term memory as well as long term and sensory memory. We are focused on a lot of the topics mentioned on this blog. I find it pretty interesting how it mentioned in this blog about rehearsing digits over and over so you are able to remember them. We are actually learning about chunking. Chunking can increase the amount of information we hold in our short-term memory. Chunking can help you able tol hold more in your short- term memory. Short-Term memory also involves: Imaging, remembering, and problem solving. I thought it was interesting how this blog mentioned that those who have alzeimers and and Schizophrenia have a reduced quality of life because they really do and its sad. Our working memory seems to be very important and it seems it involves a lot. If our short-term memory was impaired we would be lacking a lot of life quality it seems.

    1. Hello Sarah! Life without short term memory is quite debilitating. Have you ever heard of patient H.M.? In the 1950’s he was suffering from epileptic seizures, and doctors decided that he should get radical brain surgery to alleviate his epilepsy. As the brain observatory website states, “Soon after the operation, it became apparent that he could no longer recognize hospital staff, he did not remember the way home, he did not remember newspaper articles he had just read, nor the crossword puzzles he had solved; otherwise, he was completely normal. Since the time of the surgery, more than five decades of scrupulous neuropsychological research examined the nature of patient H.M.’s amnesia which proved to be both persistent and remarkably selective.” His story is so remarkable and has been the subject of many neuroscience discussions about memory and amnesia. When patient H.M. died, he donated his brain to neuroscientists, who have been studying it closely every since. Check out more about H.M. here: http://thebrainobservatory.ucsd.edu/hm

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