4 Questions About Molecular, Cellular, and Circuit Mechanisms of Cognitive Enhancement

 

Repairing neurological cellular systems is critical for memory and learning recovery after traumatic brain injuries (TMIs) such as stroke. Although the mechanisms of plasticity in the brain after TMIs are not well understood, researchers like Alcino Silva, PhD, are investigating molecular memory systems, their common signaling pathways, and how they relate to neurodevelopmental and adult neurological diseases.

This is the topic of his session at the upcoming 144th Annual Meeting of the American Neurological Association (ANA) in October 2019.1 Neurology Consultant caught up with Dr Silva before his session to gain insight into his research.

Alcino Silva, PhD, is a UCLA Distinguished Professor in the Departments of Neurobiology, Psychiatry & Biobehavioral Sciences, and Psychology and is Director of the Integrative Center for Learning and Memory Brain Research Institute at the University of California in Los Angeles.

NEUROLOGY CONSULTANT: Can you give us an overview of your session? What molecular memory systems will you discuss?

Alcino Silva: In my talk, I will discuss three key ideas. First is the idea that we need to bridge molecular and cellular neuroscience studies of memory with systems neuroscience studies of memory. This was made possible by new tools that can be used to manipulate molecular mechanisms with extraordinary temporal and cellular precision. With these tools, we can manipulate molecular function to probe questions that have been traditionally in the purview of systems neuroscience. The second idea that I will discuss in my talk reflects recent research conducted by my laboratory and the Carmichael and Shohami laboratories. Our laboratories have shown that molecular mechanisms of memory can be leveraged to enhance recovery after brain injury, including stroke and TBI in mice. We have some indirect evidence that this may also be true in humans.

NEURO CON: What are the common signaling pathways of these molecular memory systems?

AS: Research on the molecular and cellular mechanisms of memory has identified a number of signaling systems that create, edit, or stabilize acquired information in the brain. These molecular processes often modulate synaptic changes central to the encoding and retrieval of memory. For example, the studies conducted by my laboratory and the Carmichael and Shohami laboratories implicated the transcriptional factor CREB and the CCR5 receptor in both memory and recovery. Manipulations of either molecular system could enhance memory and recovery after TBI in mice. Current clinical trials are testing the impact of a drug (maraviroc) that decreases CCR5 activation in recovery.

NEURO CON: How do they relate to neurodevelopmental and adult neurological diseases?

AS: There is now extensive evidence that many of the molecular mechanisms involved in memory are also involved in cognitive disorders. Many of the proteins that modulate and modify synaptic function have been implicated in disorders that disrupt cognitive function, including neurodevelopmental and adult neurological diseases. For example, we have published previously that overactivation of CCR5 contributes to the cognitive deficits associated with AIDS, and mutations in a gene that encodes a CREB binding protein are known to cause Rubinstein-Taybi syndrome.

NEURO CON: What is the key take-home message from your session?

AS: The key take-home message is that we are entering an incredibly exciting new era in neuroscience research of memory, where we will be able to bridge molecular and cellular studies with systems studies of memory and where we will be able to transition from the study of single memories to studies of how the brain structures and integrates different memories.  This will have a real impact in basic research and, perhaps more important, on our ability to develop treatments for a number of disorders, including stroke and TBI.

For more information about the ANA’s Annual Meeting or to read more about Dr Silva’s session, visit the ANA’s website: https://2019.myana.org.

Reference:

  1. Silva A. Genetic manipulations of CCR5 and the multifaceted molecular cellular and circuit mechanisms of cognitive enhancement: a caution. Talk will be presented at: ANA 2019; October 13-15, 2019: St. Louis, MO. https://2019.myana.org/sites/default/files/docs/2019/ana19_advanceprogram.pdf.