Neurons in the brainstem promote REM sleep and trigger brainwaves that might cause dreaming

Dr. Amanda (Mandy) Schott was the lead author on this study. As a researcher, Mandy is most interested in defining neural circuits, and how specific populations of cells communicate to generate essential human behaviors such as sleep.

or technically,

A medullary hub for controlling REM sleep and pontine waves

[See Original Abstract on Pubmed]

Authors of the study: Amanda Schott, Justin Baik, Shinjae Chung & Franz Weber

Rapid eye movement (REM) sleep is the sleep state that most people associate with dreaming, however REM sleep has many other essential functions. While REM makes up only about 20-25% of our nightly sleep, it is vitally important for memory, emotional processing, and other functions we have yet to understand. This is true not just for humans, but all mammals and maybe even birds and reptiles! To facilitate all these functions of REM, the brain is highly active during this sleep state. In fact, during REM sleep, brain signals look more similar to wake than non-REM sleep. Because of this, REM sleep is sometimes called paradoxical sleep because paradoxically, the brain is so active during rest. 

Surprisingly, we still know very little about how the brain switches from low-activity non-REM sleep to high-activity REM sleep. Moreover, during REM sleep there are sometimes sporadic brain waves that seem to be important for normal brain function but whose precise role is still not totally clear. P-waves are one such waveform that is caused by lots of synchronous neuronal activity in the back of the brain, in a brainstem region called the pons. From the pons, P-waves travel forwards in the brain to brain regions important for forming and storing memories, and also areas involved in visual processing. These P-waves are interesting because they occur only during REM sleep, and are proposed to be involved in dreaming and the memory functions of REM sleep. A paper by recent NGG graduate Dr. Amanda Schott investigated two major unknowns in REM sleep research: 1) What neurons and brain regions are involved in generating REM sleep, and 2) What neurons and brain regions are involved in generating P-waves. Is it possible that one set of neurons could do both? 

While we know of several brain regions in the brainstem that regulate REM sleep, most of them consist of inhibitory neurons, meaning they “turn off’ other brain regions to promote REM sleep. Dr. Schott, however, found a highly unusual group of excitatory neurons in part of the brainstem called the dorsal medial medulla (dmM). These excitatory neurons can “turn-on” other neurons they make connections with. These dmM excitatory neurons were only active during REM sleep, suggesting they may be involved in  promoting REMs sleep. In addition, dmM neurons project their axons and send signals to the part of the pons that is known to generate p-waves. In fact, the dmM neurons were active at the same time the p-waves occurred suggesting that the dmM excitatory neurons could be involved in the generation of p-waves too! Dr. Schott next wanted to directly manipulate the activity of these neurons to see if they could cause transitions to REM sleep or cause generate p-waves. 

Using a modern neuroscience technique called optogenetics, Dr. Schott was able to cause the neurons in the dmM to fire when a laser light was shined over them through an optic fiber. She simultaneously determined if the mouse was awake, asleep, or in REM sleep by measuring the mouse’s brain waves using electroencephalography, or EEG. She found that stimulating these neurons caused the mouse to enter REM sleep, and also increased the length of REM sleep episodes. Shining the laser light also caused a p-wave to be generated when the light was shined about 60-100% of the time when the mouse was sleeping. Experimentally reducing the activity of the dmM neurons also decreased the amount of REM sleep, as well as the amount of p-waves. Dr. Schott interpreted these findings as evidence that dmM excitatory neurons are critical for normal amounts of REM sleep to occur, and for triggering p-waves. 

Overall, Dr. Shott’s work adds an important piece to the puzzle to our understanding of which brain regions can promote REM sleep. Her findings are an important first step in understanding which neurons generate p-waves which is ultimately necessary to understand p-wave function. This work will provide a foundation on which others (including the author of this piece!) can study the role of p-waves in REM sleep, and move closer to finally understanding how and why we dream.

About the brief writer: Emily Pickup

Emily is a 4th year PhD candidate in Dr. Franz Weber’s lab. She is interested in the biological functions of sleep. Specifically, she is interested in understanding the function of REM-specific p-waves. The large pontine waveform implicated in memory consolidation discussed in the brief above.

Interested in learning more about REM sleep and p-waves? See the original paper here.

Controlling serotonin circuits in the brain with light manipulates mice into approaching or avoiding rodent bullies

or, technically, 
Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat. [See the original abstract on PubMed]

Authors: Collin Challis, Sheryl G. Beck, Olivier Berton

Brief prepared by: Collin Challis
Brief approved by: Isaac Perron and Yin Li
Section Chief: Shivon Robinson
Date posted: May 3, 2016 

Brief in Brief (TL;DR)

What do we know: Serotonin—a 'happiness' molecule in the brain—is important for making social decisions. The ventromedial prefrontal cortex is important for deciding what emotion we attach to things or people. 

What don’t we know: The specific way the brain is wired to control serotonin when we are deciding to approach or avoid a stranger. 

What this study shows: We can control whether a mouse approaches or avoids a new social partner by changing the activity of prefrontal cortical neurons that communicate with cells that inhibit serotonin neurons. 

What we can do in the future because of this study: We could find out if dysfunction in this brain wiring contributes to social symptoms of mood disorders and whether changing activity of this circuit can improve behavior. Future findings could also determine how changing the activity of this brain pathway affects serotonin actions in other brain regions, both long- and short-term. 

Why you should care: Current antidepressants, which broadly target serotonin in the brain, do not work well for many people. Instead of affecting all serotonin in the brain, new treatments that target specific parts of the brain (like the regions described here) may be more effective at treating patients with mood disorders.

Brief for Non-Neuroscientists

When we meet strangers, we make social decisions, including whether we want to approach or avoid them. These are based on social judgments made immediately and often unconsciously. People that are diagnosed with mood disorders, such as depression and anxiety disorders, often excessively avoid other people. Therefore, understanding how these social decisions are made can help us design new therapies to treat disorders involving skewed social decisions. Researchers have shown that altering levels of serotonin—a molecule in the brain thought to contribute to 'happiness'—can influence these decisions; however, scientists do not know which parts of the brain communicate to control this. In our study, we investigated how communication between a brain area important for processing social information (the prefrontal cortex) and a brain area that provides serotonin to the rest of the brain (the dorsal raphe) can affect social approach or avoidance decisions in mice. With a technique called optogenetics, which uses light from a laser to either increase or decrease communication between the prefrontal cortex and the dorsal raphe, we were able to change the social decisions made by mice. Understanding how brain wiring affects social behavior will improve our comprehension of mood disorders, such as depression, which may allow development of better therapies to treat those people affected.

Brief for Neuroscientists

Though it has long been known that serotonin can alter social perception, the underlying neural circuits that control serotonergic output during social interaction are complex. Previous mapping studies have shown that the ventromedial prefrontal cortex (vmPFC), an area of the brain believed to be important for encoding emotional value, sends excitatory projections to the serotonergic dorsal raphe nucleus (DRN). In this study, we first show that these vmPFC afferents actually synapse directly on GABA neurons in the DRN that then locally inhibit serotonin neurons. We then used optogenetics to manipulate this specific and direct pathway from the vmPFC to the DRN during social defeat, a paradigm that exposes mice to physical and sensory contact with a larger, more aggressive strain of mice and induces a long lasting form of social avoidance. We found that blocking vmPFC inputs to the DRN, thus disinhibiting serotonin neurons, prevented the social avoidance typically observed after defeat. Conversely, when we optogenetically activated the vmPFC terminals, these mice displayed strong social avoidance and a considerable delay in their decision to approach a social partner. Dissecting the role of the vmPFC-DRN in social decisions has implications for the social symptoms observed in mood disorders as well as the development of novel therapeutic treatments for these behaviors.