Rapid dynamics of hippocampal spatial representation in echolocating bats

For a recent neuroscience journal club, I presented several papers on echolocating bats. Under the premise that “bats are awesome” (F. Collman, personal communication), what follows are the major points from my presentation. The slideshow below contains parts of my presentation including figures from several relevant papers. A disclaimer – I will be vastly oversimplifying the research, and presenting only a fraction of what the authors discovered and discussed. For less concise descriptions of the research in question, interested persons should read the appropriate papers. The hippocampus is a region of the brain critically important for episodic and spatial memory. Patients without their hippocampi (like the famous patient H.M.) cannot form new episodic memories. Patient case studies such as H.M’s sparked a keen interest in the hippocampus amongst neuroscientists, and there have been great strides in elucidating the neural circuitry within the hippocampus. The question of exactly how that neural circuitry encodes episodic and spatial memory is a matter for many lines of ongoing research and much debate.

One well described phenomenon within the hippocampus, that may play a critical role in the spatial component of spatial memory formation, are hippocampal neurons termed “place cells”. These neurons are driven when the animal passes through a particular region of its environment. Earlier work in rodents demonstrated that when an animal is placed within a particular environment, its place cells tile the entire area, tracking the animal’s movements. The spatial region that any given place cell (called the “place field”) encodes is flexible – changes to the environment (i.e. moving landmarks, changing wall colors, altering odors) will alter the place field. Introducing an animal into a brand new environment will cause an individual place cell to generate a new place field, however returning that animal to the old environment will recall the original place field. Theoretically, the location information provided by place cells could be utilized in the generation of memories. Place cells fire as you move through the world, and the order in which the population fires could be stored as a memory of movement through space. Exactly how this storage could be achieved, and where in the brain it takes place, is the subject of many ongoing research projects. It’s also not what the rest of this post will be about.

Instead, we’ll turn to a slightly different question – one of how sensory information influences the structure of the place fields. Another persistent research question is what exact inputs generate the place field. It seems like common sense that sensory information would play some role in establishing and maintaining the place field, and in causing a place cell to fire as the animal moved through the appropriate place field. As I mentioned about, it is known that altering the sensory information within the environment will cause place cells to change their fields. However, these changes occurred over long time scales (the order of minutes to days). Researchers from the University of Maryland were interested in much quicker changes in place fields – namely, how place cells responded to newly arrived sensory information. Do place cells rapidly alter their fields based on temporally precise sensory events?

To answer this question, the researchers, Nachum Ulanovsky and Cynthia Moss turned to the big brown bat (Eptesicus fuscus). These echolocating bats, sized approximately 10 cm, produce echolocation calls on average once every 260 ms, which the bats preferentially use to provide sensory information about their environment. These calls, the authors reasoned, were the perfect sensory event with which they could investigate the possibility that the spatial precision of a place field is rapidly altered by sensory information. As a first step, the authors conclusively demonstrated place cells within the bat hippocampus; recording place fields while bats crawled along an angled wall, using echolocation to hunt for food (Ulanovsky and Moss, 2007). They then looked closely at the activity of place cells immediately after each echolocation call, and discovered that as time passed following a call, place fields got bigger (see Ulanovsky and Moss, 2011). In other words, after an echolocation call, place cell was pickier about the precise spatial region through which a bat had to move in order for that place cell to fire. This enhanced spatial precision lasted for ~ 300 ms after each call, demonstrating for the first time, rapid changes in hippocampal place fields tied to the influx of sensory information. The time constants of these changes (~300 ms) are much more rapid than those previously reported, which were on the order of seconds.

[slideshare id=11261716&doc=echolocationblogpresentation-120125174833-phpapp01]

Take home message:

Place cells can rapidly integrate incoming sensory information, tuning the spatial selectivity of their place cells to match the spatial acuity of the new information. The spatial selectivity decays between sonar calls as the animal has to rely on less accurate sensory information (or even do without any sensory information, depending on the availability of and preference for non-echolocation based sensory information).

What does this mean for non-bats? The research does make some interesting predictions for rodent or primate studies – namely that quickly providing visual information (perhaps by rapidly flashing on a strobe light) would lead to similar rapid place cell dynamics. However, whether the varying acuity of sensory information provides ongoing regulation of place fields in a more physiological context, is unclear. For example, animals with fovea (such as humans and non-human primates) can increase the acuity of visual information for a particular region of space by directing their fovea towards that region. Similarly, the process of attention is characterized by enhancements in the neural representations of sensory information. How these might influence the spatial selectivity of place fields remains an open question, as does the effect of rapid place field dynamics on the creation of spatial and episodic memory.

Ulanovsky and Moss (2007). Hippocampal cellular and network activity in freely moving echolocating bats. Nat. Neurosci 10(2): 224-233.

Ulanovsky and Moss (2011). Dynamics of hippocampal spatial representation in echolocating bats. Hippocampus 21:150-161.

An Open Letter to Michael Keller

Mr. Keller: As Publisher of both the Stanford University Press and HighWire Press (a division of the Stanford University Libraries), you understand the value of the free and broad dissemination of knowledge.

You must also appreciate the threat that the Research Works Act (HR 3699) poses to the open exchange of ideas. This exchange is central to scientific progress and is the most fundamental means the scientific community has to return the public investment on our research. In limiting access to publicly-funded research, this act stands against the stated mission of both Stanford University Press and HighWire Press, as well as the motto of Stanford University itself.

I therefore urge you to join other respected members of the Association of American Publishers, including AAAS, the MIT Press, and the University of California Press, in publicly stating their opposition to the Research Works Act.

Sincerely, Kelly Zalocusky

PhD Candidate Stanford University Neuroscience Program

-------------------------------------------------------------

In case Mr. Keller is not an avid NeuroBlog reader, I have also sent him the letter directly. I encourage my fellow NeuroBlog readers to do the same. Really, truly--feel free to copy, paste, and send this exact letter. Michael A. Keller can be reached at Michael.Keller@Stanford.edu

Admin Note:

As a colleague and fellow PhD Candidate at Stanford University, I whole-heartedly agree Ms. Zalocusky's sentiments, and I applaude her for speaking out against the Research Works Act (HR 3699). I hope that readers will join with us in contacting both members of the American Association of Publishers, as well as our elected representatives in national government, in protest of the Research Works Act.

Astra Bryant

PhD Candidate Stanford University Neuroscience Program

Stanford At SfN11 - Wednesday Schedule

For those of you still at SfN11 on Wednesday, be sure to visit the final posters from Stanford Neuroscience.

The Stanford Neuroscience affiliates presenting their research on Wednesday, Nov 16 are:

Posters

2:00-3:00 pm: Helen Bronte-Stewart

Program#/Poster#: 888.06/AA34

Title: Evidence for alpha and beta band hypersynchrony at rest in the GPi in generalized dystonia and its attenuation during high frequency GPi DBS in DYT3+ dystonia

Location: Hall A-C

4:00-5:00 pm: Corrina Darian-Smith

Program#/Poster#: 917.04/SS4

Title: Alterations to corticospinal projections following dorsal rhizotomy in the macaque monkey

Location: Hall A-C

Stanford at SfN11 - Tuesday Schedule

What has the Stanford Neuroscience community been up to? Find out by visiting our presentations and posters at SfN2011!

The Stanford Neuroscience affiliates presenting their research on Tuesday, Nov 15 are:

Presentations

9:10-9:45 am: Rob Malenka

Title: Function and plasticity of distinct subtypes of dopamine neurons

Location: Ballroom A

Posters

8:00-9:00 am: Cora Ames (Shenoy Lab)

Program#/Poster#: 591.17/MM25

Title: Neural dynamics of movement execution following incomplete or incorrect planning

Location: Hall A-C

4:00-5:00 pm: Izumi Toyoda (Buckmaster Lab)

Program#/Poster#: 672.04/Y3

Title: Possible mini-seizures in a rat model of temporal lobe epilepsy

Location: Hall A-C

Stanford at SfN11 - Monday Schedule

What has the Stanford Neuroscience community been up to? Find out by visiting our presentations and posters at SfN2011!

The Stanford Neuroscience affiliates presenting their research on Monday, Nov 14 are:

Presentations

10:15-10:35 am: Marius Wernig

Title: Novel reprogramming methods and ways to bypass the pluripotent state by directly converting non-neuronal somatic cells into functional neurons

Location: Ballroom B

Posters

8:00-9:00 am: Brittany Burrows

Program#/Poster#: 405.13/YY63

Title: Effects of reward and FEF microstimulation on choice and visually guided saccades during a free-choice task

Location: Hall A-C

9:00-10:00 am: Lynette Foo (Barres Lab)

Program#/Poster#: 330.02/A32

Title: Development of a novel method to purify and culture rodent astrocytes

Location: Hall A-C

9:00-10:00 am: Nick Steinmetz (Moore and Boahen lab)

Program#/Poster#: 379.06/OO26

Title: Pattern of presaccadic modulation of visual responses in macaque V4 measured simultaneously across cortical layers

Location: Hall A-C

10:00-11:00 am: Gary Steinberg

Program#/Poster#: 362.19/EE19

Title: Functional engraftment of CHR2-expressing human neural stem cells in experimental model of stroke

Location: Hall A-C

1:00-2:00 pm: Andreas Rauschecker

Program#/Poster#: 486.01/OO11

Title: Position-sensitivity in the VWFA measured using fMRI pattern-classification and intracranial recordings in humans

Location: Hall A-C

2:00-3:00 pm: Josef Parvizi

Program#/Poster#: 486.02/OO12

Title: Ventral occipito-temporal circuits for word form recognition elucidated using subdural electrode recordings in humans

Location: Hall A-C

Stanford at SFN11: Sunday Schedule

What has the Stanford Neuroscience community been up to? Find out by visiting our presentations and posters at SFN2011! The Stanford Neuroscience affiliates presenting their research on Sunday, Nov 13 are:

Presentations

8:30-8:45 am: Matt Kaufman (Krishna Shenoy lab)

Title: Changes of mind in a decision-making maze task in monkey

Location: 146A

10:15-10:35 am : Sam McClure

Title: Behavioral implications of relative value coding in the human brain

Location: 207B

1:45-2:00 pm: David Kastner (Stephen Baccus lab)

Title: Mechanism and circuitry underlying retinal sensitization

Location: 152B

Posters

8:00-9:00 am: Mehrdad Shamloo

Program#/Poster#: 152.01/W7

Title: Xamoterol rescues memory deficit in mouse model of down syndrome by activation of beta-1 adrenergic receptor.

Location: Hall A-C

9:00-10:00 am: Jake Rinaldi (Jennifer Raymod lab)

Program#/Poster#: 183.14/QQ25

Title: Climbing fiber activity as an error signal for VOR motor learning

Location: Hall A-C

10:00-11:00 am: Paul Buckmaster

Program#/Poster#: 154.03/Y18

Title: Temporal lobe epilepsy in California sea lions.

Location: Hall A-C

1:00-2:00 pm: Lisa Gunaydin (Karl Deisseroth lab)

Program#/Poster#: 306.05/YY16

Title: Bidirectional modulation of social behavior by optogenetic tuning of mesolimbic dopamine circuitry

Location: Hall A-C

1:00-2:00 pm: Emily Ferenczi (Karl Deisseroth lab)

Program#/Poster#: 306.09/YY20

Title: Stability of optogenetic tool deactivation kinetics under varying stimulation conditions

Location: Hall A-C

2:00-3:00 pm: Kelsey Clark (Tirin Moore lab)

Program#/Poster#: 272.18/JJ23

Title: Role of dopamine-mediated activity in the frontal eye field in spatial working memory

Location: Hall A-C

2:00-3:00 pm: Rohit Prakash (Karl Deisseroth lab)

Program#/Poster#: 306.10/YY21

Title: Development of two-photon optogenetic control by integrating optics with molecular engineering

Location: Hall A-C

3:00-4:00 pm: Lief Fenno (Karl Deisseroth lab)

Program#/Poster#: 306.07/YY18

Title: Combinatorial optogenetics with integrated spectral and temporal control

Location: Hall A-C

3:00-4:00 pm: Dan O'Shea (Krishna Shenoy lab)

Program#/Poster#: 306.11/YY22

Title: Optogenetic control of excitatory neurons via a red-shifted opsin in primate premotor cortex

Location: Hall A-C

4:00-5:00 pm: Joanna Mattis (Karl Deisseroth lab)

Program#/Poster#: 306.12/YY23

Title: Principles for optogenetics derived from direct comparative analysis of microbial opsins

Location: Hall A-C

Stanford Neuro @ SFN2011

What has the Stanford Neuroscience community been up to? Find out by visiting our presentations and posters at SFN2011! The Stanford Neuroscience affiliates presenting their research on Saturday, Nov 12 are:

Presentations

3:15-3:35 pm : John Huguenard (aka our valiant Program Director)

Title: Role for astrocytic GABA transporters in regulating synaptic activation of GABAB receptors in thalamus

Location: 202B

Posters

1:00-2:00 pm: Jaimie Adelson

Title: Lack of MHCI ligands or PirB receptor is neuroprotective following stroke.

Program#/Poster#: 62.01/FF7

Location: Hall A-C

Chronicles of a Graduate Student Let Loose in Europe (Part 2)

Georgia Panagiotakos is a senior graduate student in the labs of Drs. Ricardo Dolmestch and Theo Palmer, where she studies mechanisms by which mutations in the voltage gated calcium channel CaV1.2 influence neurogenesis in the developing brain and contribute to the pathophysiology of autism spectrum disorders. The spring/summer Georgia attended two scientific conferences in Europe, and graciously volunteered to write a two-part blog post chronicling her experiences.

Ironically, I intended this blog post to be short and sweet. Now I’m staring back at what has amounted to a novella. Let’s move on from Greece to Germany then. The cortical development meeting (ed. note: Cortical Development: Neural Stem Cells to Neural Circuits). proved to be a source of new friends, as well as the birth of a new collaboration that would benefit my work. I returned to Stanford excited to get back to my science. A mere three weeks later found me on yet another plane (and decidedly more nervous) headed for Washington, DC - the first stop on the way to Lindau, Germany, a picturesque, tiny (read: if you are walking in any direction for longer thanten minutes without seeing water, you have been walking in circles) island in Lake Constance that was the site of the 61st Lindau Meeting of Nobel Laureates. I must admit my ignorance in saying that I had no idea there was an island in Germany prior tothis meeting. I should also take a moment here to thank one of my advisors for nominating me for this meeting. It was such an exceptional opportunity that I didn’t quite appreciate until I was actually living it. The truth of the matter is that there is relatively little that I can say to accurately convey the extent to which I enjoyed this week in Germany (I never imagined that Broca’s area would actually fail me at some point). I met new colleagues from all over the world that I envision running into at other meetings several years from now. I had dinner and lunch, respectively, with the co-discovers of one of the most fundamental techniques in use in neuroscience today, the patch clamp. I struck up relationships with other young scientists that I can see myself collaborating with for many years to come. And all this came from an email I received from my advisor some time last year that said “Hey, I’m thinking of nominating you for this thing. Would you go?”

In lieu of describing the details of this meeting, much of which was focused on science as a career path and the responsibilities we have as scientists, I’ve decided to stop my chatter here and leave you with the series of memorable quotes that I promised at the beginning. I hope you’ll find them as enjoyable as I did. You’ll see that they run the gamut from hilarious to inspirational.

I’ll start with Oliver Smithies (arguably the most adorable scientist that ever lived, the darling of the Lindau meeting, and the winner of the Prize for his work in gene targeting and homologous recombination). He was by far one of the favorites of everyone in attendance, largely because he continues to do science to this day, at the age of 86, and has managed to retain a child-like enthusiasm for science that I can only wish to maintain through grad school, let alone an entire scientific career:

• “Because I still work at the bench, I am not the director of anything. I am still a child of science.. a grad student who never grew up.”- (this one I find especially meaningful in year four of graduate school)
• “My thesis was based on a complete myth! And my paper.. never quoted. And no one ever used my method. And I never did again either!”
• “What’s the point of it all? It doesn’t matter what you do for your PhD, as long as you are having fun. If you don’t enjoy it, ask your advisor to switch you to something else. If he won’t, switch advisors!”- (a personal favorite)
• “So.. out of laziness, I invented gel electrophoresis. You may notice there are no photographs.. You see, my lab had no camera!”- Smithies flashed up a photograph of his old-school PCR machine, literally pieced together from parts of other machines tagged by the maintenance people with “NBGBGFO: No bloody good, but good for Oliver”.
• “I’m still running gels.. and I’m still running them on Saturdays”.

Next up is Ada Yonath, winner of the Prize for her work on the structure of the ribosome. I attended her small discussion session and collected these pearls:

• “For the young women concerned about doing science and having a family... my granddaughter said this about me: ‘I know she is a busy scientist, but she always makes time for me’ to her kindergarten class... right before I lectured them on ribosomes at the age of five.’”
• “There are things in life much more difficult than science, put failures and successes into perspective.”
• (on trying to disconnect yourself from the burden of being promoted) “It needs to change. Free yourself and think about science. Good science cannot happen when worrying about papers.”

For the readers of this blog, no introduction is needed for Erwin Neher, co-recipient ofthe Nobel Prize (with Bert Sakmann) for “their discoveries concerning the function of single ion channels in cells”. I had the opportunity to have dinner with Neher and lunch with Sakmann, where I learned that Neher loved running around the lab with his soldering iron making constant improvements to the rig. It sounds like not much has changed in terms of how electrophysiology is done over the years. One quote from Neher’s talk that served to put time invested into a project into perspective:

• (on how long it took them to invent the patch clamp technique) “after a very tiny struggle.. just two to three years..”

Undeniably one of the most vocal personalities at this meeting, Sir Harold Kroto, winner of the Prize in chemistry for the discovery of C60, was not shy about expressing his opinions (as you’ll undoubtedly appreciate upon reading his quotes). An interesting fun fact, it turns out that Kroto acted in a play with Sir Ian McKellan in the fifth grade! That must have been some middle school. Below is a series of quotes from his plenary session and smaller discussion session:

• “If you make people think they are thinking, they’ll love you; but if you really make them think, they’ll hate you.”
• “Enjoy your beauty whilst you may, for it will not last.. This is what I used to look like [flashes a picture of himself when he was younger]. A lot of you are young and beautiful, but eventually you will all be old and decrepit like me.”
• “Find out the evidence for everything you accept.”
• “Beware of too focused research strategies.”
• Early in the day, at his plenary lecture, Kroto provided one of the most memorable moments of the meeting, unbuttoning his salmon colored shirt on stage and eliciting a collective gasp from the audience, until everyone saw a t-shirt he made underneath depicting Darwin’s phylogenetic tree of life (a wonderfully passive aggressive way of sticking it to everyone who continues to misunderstand evolution). “I got rid of all the bumper stickers on the way to Lindau,” he exclaimed.
• “It’s true, my finding was useless. They told me, the Nobel Committee, that I might have to give it back [the prize].. but I already spent all the money!”
• “Stupid educational systems think teachers can teach thirty students exactly the same way.. How many of you have brothers and sisters? Are you all the same? Of course not!”
• “If you want to know how to give a powerpoint.. I mean how I give a powerpoint.. which of course is the best way to do it..”
• (on what drives him to do good science) “You cannot do anything second rate!”
• (on what might provide the solution to antibiotic resistance) “somebody who is doing something totally different may come up with the real solution to this problem..”
• “Knowledge cannot guarantee good decisions - but common sense suggests that wisdom doesn’t come from ignorance.”
• (possibly my absolute favorite quote from the entire meeting) “Humans - evolution has created an animal for whom rational analysis is not essential for survival.” Let’s see if developmental neuroscience can explain that one :)

Moving on, we come to Roger Tsien, who received the Nobel Prize in Chemistry for “his discovery and the development of green fluorescent protein”. He has since pioneered the development of many of the calcium imaging dyes widely used today. His plenary session was both informative and entertaining, and I have collected some of those more memorable quotes and stories here:

• (on transitioning from GFP to dsRed) “I did it for the pretty videos - but GFP was never as pretty as a gorgeous red.”
• (on having ChR2 sitting in his freezer while his graduate student toiled with trying to use ChR1 to depolarize cells) “Just because you are a Nobel Prize winner doesn’t mean you don’t have some humiliating failures. I boggled with guy’s attempt to get famous! Just because I am here and supposedly eminent doesn’t mean I don’t make mistakes.”I should note here that Tsien was a really exceptional speaker and had a certain charm about him that I am not sure that I expected prior to hearing him speak.
• (advice to young scientists) “Get regular exercise to outlive your scientific competitors.”
• (more advice) “Look for a question that gives some internal sensual pleasure.. or at least puts your neuroses to constructive use.”

Avram Hershko, who received the Nobel Prize for his work on the ubiquitin system, delivered an excellent overview of the ubiquitin pathway in health and disease. He closed his plenary talk with lessons learned throughout his career and advice for young scientists that included:

• find good mentors
• find an important subject that is not yet interesting to others (“because the big guys will get there before you”)
• some times great discoveries are made by accidental observation
• use whatever approach is necessary for your work
• never leave benchwork and your enthusiasm will stay high (he called it “a curiosity-driven adventure”)

There you have it. Overall, I have to say that what impressed me the most was how many of these laureates pursued questions simply because they were interesting to them and not because they would yield a “big result”. More impressive still is how many of them did not realize how seminal their work would turn out to be. I suppose this means that no matter how insignificant we think our science might be now (and I would argue it is easy to think this at various points throughout grad school), we might discover that other people will become interested later. So.. dream big I guess. How’s that for a positive note?

Chronicles of a Graduate Student Let Loose in Europe (Part 1)

Georgia Panagiotakos is a senior graduate student in the labs of Drs. Ricardo Dolmestch and Theo Palmer, where she studies mechanisms by which mutations in the voltage gated calcium channel CaV1.2 influence neurogenesis in the developing brain and contribute to the pathophysiology of autism spectrum disorders. The spring/summer Georgia attended two scientific conferences in Europe, and graciously volunteered to write a two-part blog post chronicling her experiences. This past month has marked the first time in my graduate career that I have had the opportunity to travel overseas for a scientific meeting and interact with giants in my field. In a stroke of remarkable luck, I was able to attend two different conferences, both of which took place in Europe. The first of these was small and specialized, an assortment of about two hundred scientists from around the world focused exclusively on understanding the mechanisms underlying brain development and the evolution of the human cortex (ed. note: the conference is question is entitled Cortical Development: Neural Stem Cells to Neural Circuits). The second meeting was quite broad, bringing together students and postdocs from over eighty countries to interact with twenty-six Nobel laureates in medicine and physiology (ed. note: this is the Lindau Nobel Laureate Meeting).

Admittedly, I approached this second meeting with some nerves (How difficult would it be to really have a stimulating scientific discussion with someone whose research interests are so distant from mine? Could I really convey the excitement I feel about what I do and the importance of neuroscience research to someone focused on understanding the structure of a protein or examining the life cycle of a virus?) - these fears proved to be moderately irrational and this experience was one that I will never forget. In telling some friends about these two wonderful experiences, I was prompted to transcribe some of what I heard into my first (and likely last) entry on the Stanford neuroblog. I needed a little pick-me-up today, so what follows is a pleasant distraction, a short description of each meeting, interspersed with a series of memorable quotes.

Surprisingly (read: not at all surprisingly), it appears that I am incapable of writing something “short”. I hope that this entry is sufficiently interesting to you to allow me some liberty with words.

During the third week of May, I flew to Greece (my homeland - conference for the win!) to attend a meeting on cortical development. I suppose I should preface everything I write here with the statement that I have been intrigued by cortical development, and how it is that specific cell types are generated and functionally connected in the developing brain, for about as long as I have been interested in neuroscience. This really reflects itself in the fact that a significant portion of my scientific career to date (young as it is) has centered around aspects of this very broad question. In light of this, the opportunity to attend this meeting was really a remarkable treat. An additional disclaimer: It didn’t hurt that the meeting was to take place on the island of Crete. And I cannot say that we didn’t take advantage of the beautiful weather and majestic Mediterranean sea - but the meeting itself proved to be on par with the exceptional location. Over the course of four days, we heard from the likes of Arnold Kriegstein, Pasko Rakic, Gord Fishell, Jeff Macklis, Arturo Alvarez-Buylla, Chris Walsh, and others, in sessions focused on stem cells, neurogenesis and neuronal differentiation, neuronal migration, circuit formation and neuronal circuits. I decided not to detail every talk here, in the interest of time (both mine and yours), and to focus instead on my impressions from the meeting now that I’ve had several weeks to ruminate.

Two over-arching themes that seem to be driving the field of cortical development really popped out for me at this meeting:

Neuronal subtype specification.

In particular, many of the talks centered around understanding the development, migration and maturation of cortical interneurons and exploring their role in sculpting cortical circuit function (a long standing interest of mine that I like to think of as a guilty pleasure of sorts). The conclusion of the series of talks surrounding this question requires me to, if I may, borrow a phrase that Jeff Macklis used during his excellent talk describing the acquisition of neocortical projection neuron identity - a “combinatorial multi-state logic” in the form of the activation or repression of specific transcription factors at different stages of development, responsiveness to guidance molecules, feedback mechanisms and neuronal activity (as beautifully depicted in a recent paper from the lab of Gord Fishell) is employed by the developing brain to generate remarkably diverse populations of interneurons that terminate in specific locations, exhibit different physiological properties and integrate into specific cortical circuits. Interesting to think about is how these strategies are integrated by individual cells as they mature and acquire their terminal fates.

Evolution of the human cortex.

The other point of emphasis at this meeting was the development of hypotheses regarding the evolution of the human cortex, in particular the expansion of the upper layers and the diversification of neuronal populations. A significant proportion of speakers, whether they were studying interactions of neural progenitor cells with the extracellular matrix, or basic mechanisms of cell division, or human-specific disease mutations, at the very least commented on how their finding might impact our understanding of human brain evolution. Arnold Kriegstein started the meeting off by presenting his beautiful work describing the behavior of outer radial glial cells, a new class of neural progenitor cell located in a separate anatomical zone in the developing monkey and human brain termed the outer subventricular zone (oSVZ). He showed us the elegant time-lapse images for which he is famous, depicting these cells translocating their somata (literally “jumping”) and subsequently dividing to give rise to daughter cells by undergoing characteristic modes of cell division. The massive expansion of the oSVZ during mid-gestation in humans prompted Kriegstein to argue the importance of these outer radial glial cells for the expansion of the human neocortex, through an increase in the number of neurons being generated. He further suggested that these different progenitor niches in the developing brain might allow for the emergence of heterogeneous cell types even at the same birthdate. That same afternoon, we heard Pasko Rakic (in a session chaired by Kriegstein himself) assert that the oSVZ is not the most important feature for the evolution of the cortex. Gauntlet thrown? We later heard from Chris Walsh, who described another approach at uncovering important players in human cortical development, the use of Next-Gen sequencing to identify disease mutations that cause cortical malformations. He went on to talk about a separate project in his lab that focused on the role secreted factors in the cerebrospinal fluid might play in instructing cell fate decisions and proliferation in the developing brain.

The meeting closed with what admittedly may have been one of my favorite talks, a beautiful story by Nenad Sestan describing the patterning of microcolumns in the developing human cortex and efforts towards completing a developing human brain transcriptome. I would be remiss if I didn’t also give a shout out to my friend and fellow Stanford neuroscience program graduate student, Alex Pollen, who (for once not talking about penile spines!) presented a wonderful poster describing his work aimed at identifying human-specific deletions of regulatory elements that may underly the evolution of human-specific brain features. Overall, I was left with the impression of a vibrant field in which a number of labs are using very different approaches to unravel the mechanisms underlying human-specific cortical expansion. It’s only fitting that I close this part with a quote from the man himself, Pasko Rakic: “It’s more complicated than I say, but they only gave me forty minutes.”