When we learn new information we use only a tiny fraction of the neurons in our brain for that particular memory trace. In order to allow the molecular study of those specific neurons we combined elements of the tet system with a promoter that is activated by high level neural activity (the cfos promoter) to generate mice in which a genetic tag can be introduced into neurons that are active at a given point in time. The tag can be maintained for a prolonged period, creating a precise record of the neural activity pattern at a specific point in time. Using fear conditioning we found that the same neurons activated during learning were reactivated when the animal recalled the fearful event. We also found that these neurons were no longer activated following memory extinction, consistent with the idea that extinction modifies a component of the original memory trace.
Supplementary Figure 1: A schematic illustrating the main finding. Slow gamma is maximal on the descending portion of the theta wave, and fast gamma peaks near the trough. Slow gamma serves to synchronize CA1 with inputs arriving from CA3, and fast gamma synchronizes CA1 with MEC input.
Replay of behavioral sequences in the hippocampus during sharp wave ripple complexes (SWRs) provides a potential mechanism for memory consolidation and the learning of knowledge structures. Current hypotheses imply that replay should straightforwardly reflect recent experience. However, we find these hypotheses to be incompatible with the content of replay on a task with two distinct behavioral sequences (A and B). We observed forward and backward replay of B even when rats had been performing A for >10 min. Furthermore, replay of nonlocal sequence B occurred more often when B was infrequently experienced. Neither forward nor backward sequences preferentially represented highly experienced trajectories within a session. Additionally, we observed the construction of never-experienced novel-path sequences. These observations challenge the idea that sequence activation during SWRs is a simple replay of recent experience. Instead, replay reflected all physically available trajectories within the environment, suggesting a potential role in active learning and maintenance of the cognitive map.
CNN News ran a segment last month on the meaning and impact of intelligence on a person’s life, as measured through a test such as the Wechsler Adult Intelligence Scale which gives an “IQ.” Dr. John Gabrieli of MIT displays brain scans that show functional differences between brains of low IQ and high IQ subjects while completing intelligence tests in an MRI scanner. The higher IQ brain shows less activity than the lower IQ brain during the same task, indicating that smarter brains are more efficient.
The findings on IQ mentioned in the report are remarkable. The standing debate on the importance of IQ is also on display here. Researchers have found that 25% of what makes one successful can be attributed to IQ -but Dr. Gabrieli points to findings that increases in IQ are linked to “a better paying job, a healthy future, more stability in your family life.” This makes the prospect of “training intelligence” to increase IQ scores all the more alluring and relevant. A demonstration of a computer working memory task that is used to “train intelligence” is featured in the segment.
You’ve probably read by now about the announcement by IBM’s Cognitive Computing group that they had created a “computer system that simulates and emulates the brain’s abilities for sensation, perception, action, interaction and cognition” at the “scale of a cat cortex”. For their work, the IBM team led by Dharmendra Modhawas awarded the ACMGordon Bell prize, which recognizes “outstanding achievement in high-performance computing”.
The journal, Frontiers in Neuroscience, edited by Idan Segev, has made it Volume 3, issue 1. Launching last year at the Society for Neuroscience conference, its probably the newest Neuroscience-related journal.
I’m a fan of it because it is an open-access journal featuring a “tiered system” and more. From their website:
The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.
[Suzanne] Corkin deliveredCryopaks to his nursing home in Windsor Locks, Connecticut.“They kept them in the freezer so that the moment he died theycould wrap his head to preserve the brain,” she says. When Molaison[ie. H.M.] died of respiratory failure at 5:05 p.m. on 8 December 2008,the plan sprang into action. A hearse took his body to MassachusettsGeneral Hospital (MGH) in Charlestown, where researchers begancollecting anatomical magnetic resonance imaging (MRI) scansof his brain at about 9 p.m.—and continued until 6 a.m.the next day, when Annese arrived on a red-eye flight from SanDiego.
Jacopo Annese, a neuroanatomist at UCSD, is planning on putting H.M.’s whole brain online on his website. But before that happens, he has a rather huge task before him:
Usinga microtome, he will slice the brain into very thin sections.“Like prosciutto,” he says, but less than 1/20 the thicknessand a lot more fragile. Annese aims to slice the brain wholeinstead of first cutting it into smaller chunks as is more routinelydone. Small chunks are much easier to work with, but the resultingslices are hard to keep in register with one another. Whole-brainslices will keep more of the tissue intact and result in a morefaithful reconstruction of the brain, he says. Annese estimates he will end up with about 2600 slices of Molaison’sbrain. He and his colleagues will mount some of these, perhapsevery 12th one to start, on extra-large glass slides—13by 18 centimeters—and treat them with a stain that colorscell bodies purple. A camera attached to a microscope will photographeach slice at 20x magnification, sufficient to distinguish differentcell types. At that magnification, photographing a single slicewill require a mosaic of about 40,000 individual images.
And there is some stress that comes from dealing with such a one-of-a-kind specimen:
But a lot could go wrong. The MRI scans revealdeterioration of the white matter, Annese says, which mightmake the slices especially delicate and prone to tearing. Aneven more nightmarish scenario is a cracked brain, he says.Sometimes, a brain will freeze unevenly and break apart—destroyingit before it can be sliced. Annese is taking every precaution,but he’s not taking anything for granted. “Cutting will makeor break the project,” he says. “But if the brain cracks, Igo back to Italy.”
A set of two articles recently came out in Science that directly visualize two different (and likely complementary) approaches to synapse specific delivery of gene products. Plasticity at specific synapses (input specificity — we’re restricting the discussion to the dendrites of the post-synaptic neuron) requires proteins (eg. new AMPA receptors) to get to those post-synaptic compartments and membranes. But the intructions for these new proteins are contained in the nucleus with the rest of the genome. Clearly, new proteins synthesized in the soma can’t just be sent everywhere, since only specific inputs (eg. particular dendritic spines) need these new proteins. How does this happen? Hence, the postulated synaptic tag.
Two approaches
Broadly, there are two approaches to synaptic tagging: 1) mRNA is distributed widely and translated locally at tagged locations; 2) protein products are distributed widely in the bodies of dendrites but only contact/off-load at tagged synaptic specializations. This News & Views gives a nice overview of the two papers, which find approach 1) in Aplysia cultures with sensorin mRNA and approach 2) in rat hippocampal neurons with Vesl-1S/Homer-1a protein. It amazes me that both were found pretty much simultaneously, but that might have more to do with the use of the photoconvertible Dendra2 protein than anything else.
With both approaches, we still don’t know why mRNA/protein is directed to a certain location. That is, we can visualize synaptic tagging but we don’t know what is the tag, its ontogeny, or the mechanism of tagging. But that might not be so important to understanding more about neural function. These new tools might allow us to image plasticity at many synapses at once, perhaps even in vivo. But before that, more work is needed… does the optical signal (from the Dendra fusion protein) correlate with degree of potentiation? Can we detect plasticity in the opposite direction, ie. synaptic depression, through another tag? (As a sidenote to approach 1), the use of 5′ and 3′ UTRs as a sort of molecular zipcode is also intriguing.)
Neuroscientists often use mousemodels to understandlearning and neuraldisease. Much of our understanding of mammalian biology comes from these amazing animals. It is commonly said that highly inbred lab mice are unintelligent. But is it true for wild mice too? In a talk last week at Harvard, Karl Svoboda referred to this fascinating YouTube video showing a mouse trained to complete an obstacle course:
Other training videos from the same trainer are available along with an official website with interesting tips about mouse training. Perhaps highly inbred lab mice are unable to replicate such feats but it is amazing to see in what detail this trainer understands mouse behavior and development:
An absolute necessity for any pet training is to understand the animal’s needs and to know about its generic behaviour, since appropriate animal training is only based on certain natural habits. For mouse agility, this means e.g. their great spatial orientation abilities and spatial memory which is worth bringing to light by relevant trick training. In nature, mice always prefer the familiar (= safe) route to their feeding site, no matter if it’s a long way round. This is also the reason why mice are unbeatable in maze tests – and a mouse agility course is nothing else than a maze without walls!
But many owners forget that if you expect your pet to show some natural habits and abilities, first and foremost the husbandry has to be species-appropriate. If your mice have to live in a small ground level cage, their three-dimensional consciousness and orientation abilities will surely be stunted or never fully develop.
neurodudes is intended to be an open forum at the intersection of neuroscience and ai. regular readers are encouraged to post appropriate material. make sure to put your name somewhere in the post.
submit a post
acknowledgements
Neurodudes thanks for their support: NorthShore Neurosciences neurology hospital.
Using Yahoo Pipes, we combined neuro/ai/cog-related RSS feeds from many sources into one, sometimes filtering along the way so as to minimize offtopic posts:
Feeds are periodically added and subtracted, but hopefully reflects the blogrolls below (but doesn't yet -- it's still under construction), except for those feeds which Yahoo Pipes had trouble processing, a list of which can be seen by checking the Pipe page.
Bayle's working on Google Reader bundles for neuroscience journals, and other neuro feeds. Like the Ultimate Neurodudes Feed, these are heavily under construction, and probably aren't very good yet.
Neurodudes is moderated by Neville Sanjana, Bayle Shanks, and Stephen Larson. Comments that you post might be delayed so that we can tell our software that it's not spam -- however, not all comments are pre-screened so don't assume that we have read them, either. Any money we make off this site is used to pay for hosting, or given to charity; if in the future we pay contributors, we will include reader-authors. None of us are medical doctors so please don't ask for medical advice. Contact us here.