Sleep suppresses brain rebalancing

Why humans and other animals sleep is one of the remaining deep mysteries of physiology. One prominent theory in neuroscience is that sleep is when the brain replays memories “offline” to better encode them (“memory consolidation”). A prominent and competing theory is that sleep is important for re-balancing activity in brain networks that have been perturbed during learning while awake. Such “rebalancing” of brain activity involves homeostatic plasticity mechanisms that were first discovered at Brandeis University, and have been thoroughly studied by a number of Brandeis labs including the Turrigiano lab. Now, a study from the Turrigiano lab just published in the journal Cell shows that these homeostatic mechanisms are indeed gated by sleep and wake, but in the opposite direction from that theorized previously: homeostatic brain rebalancing occurs exclusively when animals are awake, and is suppressed by sleep. These findings raise the intriguing possibility that different forms of brain plasticity – for example those involved in memory consolidation and those involved in homeostatic rebalancing – must be temporally segregated from each other to prevent interference.

sleeprats

The requirement that neurons carefully maintain an average firing rate, much like the thermostat in a house senses and maintains temperature, has long been suggested by computational work. Without homeostatic (“thermostat-like”) control of firing rates, models of neural networks cannot learn and drift into states of epilepsy-like saturation or complete quiescence. Much of the work in discovering and describing candidate mechanisms continues to be conducted at Brandeis. In 2013, the Turrigiano Lab provided the first ­in vivo evidence for firing rate homeostasis in the mammalian brain: lab members recorded the activity of individual neurons in the visual cortex of freely behaving rat pups for 8h per day across a nine-day period during which vision through one eye was occluded. The activity of neurons initially dropped, but over the next 4 days, firing rates came back to basal levels despite the visual occlusion. In essence, these experiments confirmed what had long been suspected – the activity of neurons in intact brains is indeed homeostatically governed.

Due to the unique opportunity to study a fundamental mechanism of brain plasticity in an unrestrained animal, the lab has been probing the possibility of an intersection between an animal’s behavior and homeostatic plasticity. In order to truly evaluate possible circadian and behavioral influences on neuronal homeostasis, it was necessary to capture the entire 9-day experiment, rather than evaluate snapshots of each day. For this work, the Turrigiano Lab had to find creative computational solutions to recording many terabytes of data necessary to follow the activity of single neurons without interruption for more than 200 hours. Ultimately, these data revealed that the homeostatic regulation of neuronal activity in the cortex is gated by sleep and wake states. In a surprising and unpredicted twist, the homeostatic recovery of activity occurred almost exclusively during periods of activity and was inhibited during sleep. Prior predictions either assumed no role for behavioral state, or that sleeping would account for homeostasis. Finally, the lab established evidence for a causal role for active waking by artificially enhancing natural waking periods during the homeostatic rebound. When animals were kept awake, homeostatic plasticity was further enhanced.

This finding opens doors onto a new field of understanding the behavioral, environmental, and circadian influences on homeostatic plasticity mechanisms in the brain. Some of the key questions that immediately beg to be answered include:

  • What it is about sleep that precludes the expression of homeostatic plasticity?
  • How is it possible that mechanisms requiring complex patterns of transcription, translation, trafficking, and modification can be modulated on the short timescales of behavioral state-transitions in rodents?
  • And finally, how generalizable is this finding? As homeostasis is bidirectional, does a shift in the opposite direction similarly require wake or does the change in sign allow for new rules in expression?

Authors on the paper include postdoctoral fellow Keith Hengen, Neuroscience grad student Alejandro Torrado Pachedo, and Neuroscience undergraduate James McGregor ’14 (now in grad school at Emory).

Hengen KB, Torrado Pacheco A, McGregor JN, Van Hooser SD, Turrigiano GG. Neuronal Firing Rate Homeostasis is Inhibited by Sleep and Promoted by Wake. Cell. 2016.

How seeing can change what you see

We sometimes take it for granted how the way we see enables us to perceive and interact with the world, but how our visual system works is amazing. It’s an intricately choreographed process – from the light that comes into our eyes, to the way that our brains carry that information and form it into an image we can understand. If brain cells are improperly connected during growth and development, or if part of the system is destroyed by injury, all kinds of visual havoc can be a result. But how does a brain get wired properly in the first place?

 In a paper in the Journal of Neuroscience last week, Professor Steve Van Hooser’s lab reported some of the effects of experience on development. The new paper shows evidence that neurons in all layers of the visual cortex aren’t just ‘born’ with the right connections between the parts of the brain that control vision. According to their data, the act of seeing itself makes changes in how the neurons process visual information. The lab is continuing their studies of brain circuits to uncover how, during development, the act of seeing changes how you see.
Clemens JM, Ritter NJ, Roy A, Miller JM, and Van Hooser SD. The Laminar Development of Direction Selectivity in Ferret Visual Cortex. J. Neurosci. 12 December 2012, 32(50): 18177-18185. 

Illuminating career paths in the sciences for high school students

On November 5th, the Van Hooser lab in the Biology Department hosted nine high school students from Hyde Park’s Boston Preparatory Charter Public School (BPCPS) for both a tour of the lab and an open question session about the specific goals of the lab’s research, and about science careers in general.

Boston Prep serves students from disadvantaged areas of Boston, with 76% qualifying for free and reduced price lunch and 92% being of minority racial backgrounds. As part of a rigorous educational program that seeks to prepare them for college and beyond, BPCPS sophmores visit various area businesses twice a year for hands-on learning about the careers open to them. The school has been nationally recognized for its academic excellence. It also bucks trends in the sciences — while nationwide there is a noted drop-off in interest in the sciences as students enter high school, particularly among young women,  (Osborne, Simon, and Collins 2003; American Assoc. of University Women, 1992), students at Boston Prep retain a high interest in the sciences throughout their tenure there, and female students actually become more interested in the sciences in high school.

Assistant Professor Steve Van Hooser led the students through a brief introduction to life in an academic science lab and his personal career path, before discussing his lab’s focus on the visual system and the impact that basic research has on everyday life and understanding. The students then took a tour of the lab, and were able to visualize neurons under the lab’s 2-photon microscope. After the visit, Steve noted, “It was terrific to be able to talk with such promising young people and to share a little of the brain science we are doing here at Brandeis.  The students asked really insightful questions about our studies, the use of animals in research, and the clinical applications of basic research.  It is exciting to think about what these students will be doing in 15 years.”

Those interested in hosting a future visit from students can contact Jenn Wolff from the Van Hooser lab (jwolff at brandeis.edu), or contact Danielle Pape at BPCPS directly ( dpape at bostonprep.org (617)333-6688 ext. 126 )

New faculty Stephen Van Hooser joins Biology Dept

Steve is back, starting this month.

Stephen Van Hooser is an alumnus of Brandeis Neuroscience Ph.D. program, graduating in 2005. After a highly productive stint as a postdoc as Duke, Steve rejoins us in May, 2010 as Biology’s newest assistant professor. The Van Hooser lab will focus on the role of visual experience in maturation and development of neural circuit, using optical and optogenetic tools.

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