For Sleep but Sleepless in Lake Arrowhead, California

For the past week, I have been residing in high altitude at the UCLA-owned resort of Lake Arrowhead, California in the San Bernardino Forest (and mountains) near LA. I was attending a scientific and professional development workshop devoted to sleep research, grantsmanship, responsible conduct of research, and networking. The theme of the workshop was “translational validity in sleep research” meaning that the focus was on appropriate animal models of sleep and disease states. The workshop has been going on for nearly 30 years organized, funded, and hosted through the efforts of Dr. Michael Chase of UCLA. Holy cow was it spectacular. I can see why my undergraduate advisor, Dr. Mary Carskadon, uses Michael’s retreat as a model for her annual retreat.

The trip began with a short trip to Manhattan Beach, its epic dining, and the Santa Monica Pier where I showed those beach boys that they really aren’t as strong as their muscles make them out to be.

When we arrived in Lake Arrowhead, we immediately began to dive into intellectual discussion. We went over and critiqued common methods to sleep deprive animals. We weighed the pros and cons of common animal models of sleep and disease, namely the fly, rat, mouse, and even cat. We even talked about the pros and cons of staying ahead of the curve. The general consensus is that it is never good to put the cart before the horse; that optogenetics and chemogenetics, two sexy approaches in neuroscience that I have discussed previously, are worthless in time and money if you do not have a sufficient hypothesis and supporting rationale. Also, using these tools is not a priori for getting funded. We also learned about some transfection techniques for activating neurons and measuring neuron activity by transfecting a rabies virus or using a recording electrode covered in a lipophilic (fat-loving) material, enabling it to be sucked up by the neuron’s membrane.

On the morning of the second day, I organized a morning boot camp. One of the workshop’s organizers, Dr. Mark Opp, had the brilliant idea to do our workouts on the zen deck. Not a bad view, eh? The zen deck was the meeting spot for our morning boot camp/bro sessions for the rest of the meeting. On the second day, I also got too cocky (and stupid) in the pool and smashed my nose on the bottom of the deep end after doing a perfect front tuck into a dive.

The Zen Deck

The scientific sessions of the workshop continued with discussions of appropriate measures of sleep homeostasis. The obvious candidates are NREM sleep saturated with slow wave activity, but Dr. Ron Szymusiak presented evidence for physiological phenomena relevant to sleep homeostasis that have been overlooked. Basically, his lab examined the firing rates of neurons in two sleep-promoting nuclei of the hypothalamus, the ventrolateral and median preoptic nuclei. Typically, these nuclei are less active during wake and even forced wakefulness, and more active during spontaneous sleep or recovery sleep after sleep deprivation. Thankfully, Ron found that this is not entirely true because a tipping point from low to high rates of firing in these nuclei can occur across an episode of forced wakefulness. I am thankful for this data set because it addresses a concern that I have had with a data set of mine that I am hoping to be publish soon.

We also had an evening discussion on ethics. Each discussion began with a short skit. Here is the skit that my group and I performed to exaggerate very inappropriate relationships between mentor and mentee.

About halfway through the conference, we were introduced to the EUREKA grant writing proposals. Basically, we were given 36 hours to write AND present an R21 (NIH system) grant that would allow for two years of work and $250,000 in allowance (excluding whatever indirect costs the university took which is normally around 50%). The committee did a fantastic job of spreading out areas of research focus, or maybe it was just a coincidence. Our group had an interesting mix of expertise and personality. However, we were able to overcome an initial mental block in proposing a hypothesis-driven research question. Our proposal aimed to investigate how sleep deprivation could further worsen brain connections and cognitive and motor learning after a stroke. At the end of the day, our grant proposal won, although all of the proposals were impressive for the short time allotted! For our winning efforts, we got a bottle of Glenvelvet.

Presenting our grant

Winners of the EUREKA grant with their prize!

Without a doubt, this workshop was one of the best smaller conferences in animal research that I have ever attended. It presented many opportunities to ask questions, respectfully refute opinions, and to remove the typically intimidating barrier between PIs and trainees.  The countdown til the next workshop is on.

Highlights from the Gordon Conference on Sleep Regulation

I have been idle the past week because I have been in Galveston, TX for a secret society meeting of sleep researchers. It wasn’t really secret, but it was an invite only conference limited to less than 200 participants worldwide. The focus of the meeting was the neural mechanisms of sleep, namely those studied in animal models. As I expected, there was a central focus on optogenetics and DREAADS, recently re-named chemogenetics. Both of these methodologies have emerged about a decade ago, but have really taken off in popularity within the past two years. Basically, optogenetics and chemogenetics utilize light (opto) or drugs (chemo) to activate certain populations of neurons in specific brain regions through the assistance of transfected bacterial and viral factors.

The trip began with fulfilling every space nerd’s dream: visiting NASA and the Mission Control Center where all of the Apollo missions launched from, including Apollo 11. This room is the most famous historical landmark in the world, not just in the US. The technology of the room reminded me of human sleep laboratories from the 60-80s. The current Mission Control Center is below this room, but we were restricted access. Regardless, we also got to see the Saturn 5 rocket. Words can’t describe this monstrosity.

Kraft Control Center

The Eagle has landed

God damn!

 

After a trip to NASA and some of the best Tex Mex that I ever had, we traveled to the Hotel Galvez–the conference locale–which is a beautifully maintained resort built in 1911! It was stunning and the ambiance reflected the decade that it was built.

The Hotel Galvez built in 1911

Sort of reminds me of the Hollywood Tower of Terror in Disney

 

The conference schedule was very intense, which is characteristic for a Gordon. Each day began at 9 AM, broke off for lunch around 12:30, resumed around 4 PM with posters, broke for dinner, re-started at 7 PM and ended with a nightly social at the hotel bar around 9:30 that usually lasted until 3 AM…..yes, sleep researchers do not by any means practice what we preach. For as much as I wanted to hang until the wee hours of the morning, I had to limit myself due to being in the middle of my Crossfit season.

The historic boardwalk

 

As for the science, here are some buzzwords and key findings presented in order of salience (to me):

1. Corollary discharge: Dr. Mark Blumberg of Iowa presented evidence that twitching–a characteristic of REM sleep, particularly in neonates–is necessary for proper brain development. In describing the mechanisms of action of twitching, corollary discharge is this idea that the signal can bypass centers of the brain regulating consciousness. This is the reason why you can’t tickle yourself. Dr. Blumberg has studied twitching in neonatal rodents using a series of illuminated electrodes to identify frequencies and movement patterns.

2. The thalamus:  The thalamus has been overlooked in recent years of sleep research. This is surprising considering that it is the major gateway for sensory and neural processing that underlie most biological processes. Luckily, Dr. Michael Halaasa from NYU studies the role of thalamic circuitry in memory and learning and the EEG waveforms, namely spindles, that drive these processes.

3. The Aplysia: I am really fascinated by research conducted in this  neurologically simple invertebrate, particularly since one of the most renowned neuroscientists of the century–Dr. Eric Kandel, a Nobel Laureate– used the Aplyasia  to study circuits of learning and memory. At this meeting, Lisa Lyons from Florida State studies learning and memory processes in the Aplyasia to examine how they are impacted by sleep loss coupled with circadian disruption. Turns out, they suffer just as much as us.

4. Astrocytes: There was a significant focus on adenosine–a neurochemical marker of sleep homeostasis released from astrocytes–and its relation to physiological sleepiness, inflammation, and memory. Dr. Jason Gerstner of UPENN also studies fatty acid metabolism in astrocytes.

5. Local sleep: This has been a salient topic in the sleep field for a few years now. The idea is that certain brain areas require more sleep–neuronal “offlining”–than others and that this phenomenon is directly proportional to the extent of use. So, you can imagine the the motor centers of athletes are in greater need of local sleep compared with those of sedentary folks.

There were plenty of other great posters and talks at the meeting, but these were certainly in my top five. Overall, I was very impressed with the quality of work and presentation at Gordon. It is as if there was a try-out for being a speaker because every talk was THAT good. This rarely happens at any scientific conference.

Great conference overall.

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