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Sleep may strengthen long-term memories in the immune system

A model of memory formation in the central nervous system (upper section) and the immune system (lower section) (credit: Westermann et al./Trends in Neurosciences 2015)

Deep (slow-wave*) sleep, which helps retain memories in the brain, may also strengthen immunological memories of encountered pathogens, German and Dutch neuroscientists propose in an Opinion article published September 29 in Trends in Neurosciences.

The immune system “remembers” an encounter with a bacteria or virus by collecting fragments from the microbe to create memory T cells, which last for months or years and help the body recognize a previous infection and quickly respond. These memory T cells appear to abstract “gist information” about the pathogens, allowing memory T cells to detect new pathogens that are similar, but not identical, to previously encountered bacteria or viruses.

Studies in humans have shown that long-term increases in memory T cells are associated with deep slow-wave sleep on the nights after vaccination. Taken together, the findings support the view that slow-wave sleep contributes to the formation of long-term memories of abstract, generalized information, which leads to adaptive behavioral and immunological responses.

How lack of sleep puts your body at risk

The obvious implication is that sleep deprivation could put your body at risk. “If we didn’t sleep, then the immune system might focus on the wrong parts of the pathogen,” says senior author Jan Born of the University of Tuebingen.

“For example, many viruses can easily mutate some parts of their proteins to escape from immune responses. If too few antigen-recognizing cells [the cells that present the fragments to T cells] are available, then they might all be needed to fight off the pathogen. In addition to this, there is evidence that the hormones released during sleep benefit the crosstalk between antigen-presenting and antigen-recognizing cells, and some of these important hormones could be lacking without sleep.”

Born says that future research should examine what information is selected during sleep for storage in long-term memory, and how this selection is achieved. This research could have important clinical implications.

“In order to design effective vaccines against HIV, malaria, and tuberculosis, which are based on immunological memory, the correct memory model must be available,” Born says. “It is our hope that by comparing the concepts of neuronal and immunological memory, a model of immunological memory can be developed which integrates the available experimental data and serves as a helpful basis for vaccine development.”

* Slow wave sleep (SWS) is the constructive phase of sleep for recuperation of the mind-body system in which it rebuilds itself after each day. Substances that have been ingested into the body while an organism is awake are synthesized into complex proteins of living tissue. Growth hormones are also secreted to facilitate the healing of muscles as well as repairing damage to any tissues. Lastly, glial cells within the brain are restored with sugars to provide energy for the brain. Longer periods of SWS occur in the first part of the night, primarily in the first two sleep cycles (roughly three hours). — Wikipedia

Abstract of System Consolidation during Sleep — A Common Principle Underlying Psychological and Immunological Memory Formation

Sleep benefits the consolidation of psychological memory, and there are hints that sleep likewise supports immunological memory formation. Comparing psychological and immunological domains, we make the case for active system consolidation that is similarly established in both domains and partly conveyed by the same sleep-associated processes. In the psychological domain, neuronal reactivation of declarative memory during slow-wave sleep (SWS) promotes the redistribution of representations initially stored in hippocampal circuitry to extra-hippocampal circuitry for long-term storage. In the immunological domain, SWS seems to favor the redistribution of antigenic memories initially held by antigen-presenting cells, to persisting T cells serving as a long-term store. Because storage capacities are limited in both systems, system consolidation presumably reduces information by abstracting ‘gist’ for long-term storage.

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DARPA selects research teams for its ElectRx neuron-sensing/stimulation program

DARPA announced Monday (Oct. 5, 2015) that it has selected seven teams of researchers to begin work on a radical new approach to healing called Electrical Prescriptions (ElectRx). It would involve a system that stimulates peripheral nerves to modulate functions in the brain, spinal cord, and internal organs, according to program manager Doug Weber.

DARPA envisions a closed-loop system aimed at monitoring and treating conditions such as chronic pain, inflammatory disease, post-traumatic stress, and other illnesses that may not be responsive to traditional treatments, using optical, acoustic, electromagnetic, or engineered biology strategies to achieve precise targeting, possibly at single-axon resolution.

Pacemakers for other organs

The oldest and simplest example of this concept is the cardiac pacemaker, which uses brief pulses of electricity to stimulate the heart to beat at a healthy rate. DARPA aims to extend this concept to other organs, like the spleen, and treat inflammatory diseases such as rheumatoid arthritis.

Fighting inflammation may also provide new treatments for depression, which growing evidence suggests might be caused in part by excess levels of inflammatory biomolecules. Peripheral nerve stimulation may also be used to regulate production of neurochemicals that regulate learning and memory in the brain, offering new treatments for post-traumatic stress and other mental health disorders.

In phase 1, the ElectRx program will focus on fundamental studies to map the neural circuits governing the physiology of diseases of interest to DARPA, and also on preliminary development of novel, minimally invasive neural and bio-interface technologies with unprecedented levels of precision, targeting, and scale.

The teams

The seven teams include a mix of first-time and prior DARPA performers.

For example, an MIT team led by Polina Anikeeva will aim to advance its research in stimulating brain tissue using external magnetic fields and injected magnetic nanoparticles to treat neurological diseases such as Parkinson’s disease, replacing surgically implanted electrodes, as KurzweilAI reported in March. When exposed to a low-frequency (100 kHz — 1 MHz) external alternating magnetic field — which can penetrate deep inside biological tissues — these nanoparticles rapidly heat up and trigger heat-sensitive capsaicin (the “hot” in peppers) receptors to stimulate neurons.


MIT | Wireless brain stimulation

The other teams are:

  • Circuit Therapeutics (Menlo Park, Calif.), a start-up co-founded by Stanford University scientists Karl Deisseroth and Scott Delp, plans to further develop its experimental optogenetic methods for treating neuropathic pain, building toward testing in animal models first.
  • A team at Columbia University (New York), led by Elisa Konofagou, will pursue fundamental science to support the use of non-invasive, targeted ultrasound for neuromodulation. The team aims to elucidate the underlying mechanisms that may make ultrasound an option for chronic intervention, including activation and inhibition of nerves.
  • A team at the Florey Institute of Neuroscience and Mental Health (Parkville, Australia), led by John Furness, will seek to map the nerve pathways that underlie intestinal inflammation, with a focus on determining the correlations between animal models and human neural circuitry. They will also explore the use of neurostimulation technologies based on the cochlear implant — developed by Cochlear, Inc. to treat hearing loss but adapted to modulate activity of the vagus nerve in response to biofeedback signals — as a possible treatment for inflammatory bowel disease.
  • A team at the Johns Hopkins University (Baltimore), led by Jiande Chen, aims to explore the root mechanisms of inflammatory bowel disease and the impact of sacral nerve stimulation on its progression. The team will apply a first-of-its-kind approach to visualize intestinal responses to neuromodulation in animal models.
  • A team at Purdue University (West Lafayette, Ind.), led by Pedro Irazoqui, will leverage an existing collaboration with Cyberonics to study inflammation of the gastrointestinal tract and its responsiveness to vagal nerve stimulation through the neck. Validation of the mechanistic insights that emerge from the effort will take place in pre-clinical models in which novel neuromodulation devices will be applied to reduce inflammation in a feedback-controlled manner. Later stages of the effort could advance the design of clinical neuromodulation devices.
  • A team at the University of Texas, Dallas, led by Robert Rennaker and Michael Kilgard, will examine the use of vagal nerve stimulation to induce neural plasticity for the treatment of post-traumatic stress. As envisioned, stimulation could enhance learned behavioral responses that reduce fear and anxiety when presented with traumatic cues. Dr. Rennaker is a U.S. Marine Corps veteran who served in Liberia, Kuwait and Yugoslavia.