Ramirez, Liu et al. (2013) and Liu, Ramirez et al. (2013)


Ramirez, Liu et al. (2013). Creating a false memory in the hippocampus. Science, 341(6144): 387-391.

Liu, Ramirez et al. (2013). Inception of a false memory by optogenetic manipulation of a hippocampal memory engram. Phil Trans R Soc B, 369(1633): 20130142

To be fair, one of these papers reviews the other as well as the Liu, Ramirez, et al. paper I’ve already reviewed. But A) I read both, and B) I need to make up ground in advance for the 6 months I’ll need to re-read, understand, and review Marr’s 1971 paper.

I highly recommend playing the theme music to Inception while reading this paper and/or blog post.



Denny et al. (2014) and Cazzulino et al. (in press)


Denny et al. (2014) Hippocampal memory traces are differentially modulated by experience, time, and neurogenesis. Neuron, 83(1): 189-201.

Cazzulino et al. (accepted for publication). Improved specificity of hippocampal memory trace labeling. Hippocampus.

Denny et al. used a different method of memory trace labeling as do the Garner et al. and Liu, Ramirez et al. studies. However, it’s the same principle. Here, instead of removing Dox from the diet to label memory traces, the authors inject ArcCreERT2 mice with an estrogen receptor antagonist (in this case, it was tamoxifen) which in turns induces DNA activation. This only happens, however, in those cells that are actively producing the protein in the promoter region of the transgene: Arc. Arc is an immediate early gene expressed in cells that have recently been highly active. Thus, the authors targeted these recently active cells using this system and were able to express in them a protein of interest, e.g. eYFP. After tagging hippocampal neurons involved in memory encoding with eYFP, (more…)

Pytte et al. (2008)

Citation: Pytte et al. (2008). Regulation and function of neuronal replacement in the avian song system. In: Zeigler HP, Marler P, editors. Neuroscience of Birdsong. Vol. 28. Cambridge University Press; 350–366.

Another brief review due to a presentation tomorrow.

Today’s paper is a book chapter co-authored by my doctoral advisor, Dr. Carolyn Pytte.

The authors review the literature about the possible causes and function of neurogenesis in the songbird system.

Yiu et al. addressed the question of how certain neurons in the amygdala will be recruited into memory traces while most other amygdala neurons won’t, the answer being their relative levels of excitation at the time of memory occurrence.

Dr. Pytte’s has focused on neurogenesis in the song system of the zebra finch. In addition to the avian song system, neurogenesis also occurs, of course, in the mammalian hippocampus, my main region of focus. In both systems, more neurons that are born in adulthood die than those that survive and integrate into the surrounding circuitry. So why do particular neurons survive while others die?

In this case, the authors suggest that it is those neurons who have won the audition:


More specifically, the authors write:

“Neurons with response properties consistent with optimal song structure are cast while those that do not fit the part are rejected, prompting more neurons to be auditioned.”

So what are these response properties? If the conclusions of Yiu et al. are to be extended to the hippocampus, and adult-born neurons, it would likely be that more excitable neurons, perhaps more specifically with shorter response latencies or reduced spike frequency adaptation, would survive and become incorporated into memory traces. Interestingly, all young, adult-born neurons are hyper-excitable. They’re even excited by GABA.

So, are certain adult-born neurons in either the avian song system or the hippocampus significantly more excitable than their peers? Or is the excitation described by Yiu et al. transient and probabilistic? Perhaps those cells incorporated into a trace were doing the right thing at the right time.


Garner et al. and Liu, Ramirez et al. (2012)


Garner et al. (2012). Generation of a synthetic memory trace. Science, 35(6075): 1513-1516

Liu, Ramirez et al. (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature, 484: 381-385

Two papers today because they’re relatively quick reads, were published at the same time, are very similar and are equally awesome (I’m also 5 behind on the whole 366 thing). First, a word about Dox. In 1992, a paper was published outlining how to drive or repress the transcription of certain genes with what’s called a tetracycline-controlled transactivator (tTA). In what’s called the Tet-Off version of this system, the presence of doxycycline will inhibit specific genes from being transcribed. However, without Dox, those same genes are free to be transcribed. Both of these papers used this system in combination with c-fos promoter to manipulate memory traces in a very interesting way. Without Dox, neurons that were actively transcribing c-fos, that is, highly active cells, would synthesize a certain protein of interest. (more…)

Memory engram storage and retrieval. Tonegawa, et al. (2015)

In my first post, in a long, loooooong time, I’ve decided to join the #366papers group on Twitter and read a paper every day (due to the vacations recently booked, I know I’ll fail). I figured to keep this blog alive and to keep me writing something other than grants, I would post short, daily reviews, and perhaps longer reviews after finishing a group of papers. I’ll likely revisit papers multiple times as I learn more. I’m interested to see how my analyses will change with time. So here, I’ll start with a review on a topic I find very exciting: the identification of memory engrams. (more…)

Mind(s) of Your Own

The prominent debate in the young years of neuroscience was whether or not the brain had specialized functional regions or whether the brain as a whole was responsible for all cognitive functions.

Franz Joseph Gall was the first to assert the radical notion that all behavior emanated from the brain and that specific regions of the cerebral cortex (the large, convoluted structure on top of many pictures of the brain) controlled specific functions. Though, these assertions would be shown to hold water, he falsely viewed the brain as being synonymous to a muscle, with specific areas getting larger with use, which would cause the skull above these areas to bulge, meaning that the surface of the skull could give information about one’s mental state. This became known as phrenology and though the idea of the skull’s shape being indicative of mental capabilities has been conclusively discredited, Gall’s first two assertions have been supported.

In support of Gall’s claims that the brain contained specialized functional areas came the research of Pierre Paul Broca of France and Karl Wernicke of Germany. These two men studied aphasias, which are disorders of language. Broca discovered that patients who displayed difficulty in generating speech, yet had no ailment of the mouth or vocal cords, often had a lesion (damage, such as that caused by stroke) in a very specific site in the left cerebral hemisphere. Wernicke’s patients, who could speak, but not understand language, also had lesions in another specific site of the left hemisphere. Wernicke thus came to the conclusion that the brain was a parallel distributed processor, meaning that complex functions, such as language, are the result of different brain regions working in both serial and parallel manners.

In using using this model of cognitive function, Wernicke successfully predicted another aphasia called conduction aphasia in which these areas were intact, but the connections between them were compromised. Patients with this condition generate nonsensical speech, despite being able to form words and understand language.


Broca’s and Wernicke’s areas. Source

If understanding and generating language takes place solely in the left hemisphere, then what occurs at these places on the right hemisphere? (more…)

Ending the War on Drugs: How Studying the Brain Gives Us Optimism for an Effective Drug Policy


In complete contrast with his brother’s views about drug policy, Christopher Hitchens expresses a more libertarian view, criticizing and advocating an end to the War on Drugs in the United States and Britain. In conversation with David Frum, it is pointed out how if drugs were legalized, addiction rates may increase. Well, why the hell should we ever advocate for a policy that would have such a result? (more…)

Do You Have a Moment To Talk About Science?

I’m going to step away from the two sensational articles I’ve written on drug addiction and decision making to discuss some feedback I’ve been getting about some of the articles I’ve posted. Don’t worry, I will wrap up my discussion on drugs soon.

Have you ever been told something you were quite surprised by and didn’t want to believe at all, only to see over time that it was in fact true? Perhaps, at first, you denied it vehemently. Then you accepted it begrudgingly. Then you regarded it as a a mere fact. Perhaps you have even come to a point where you find it interesting and take a pride in it.

For example, maybe you’ve been told that you look just like someone else whom you’d rather not look like, perhaps a celebrity that you don’t see as particularly attractive. At first you may be insulted and claim you look nothing like them. Over time, however, enough people point out the resemblance and you begin to see objective truth in their observations and eventually impersonate this celebrity every year on Halloween. Though I was mortified when it was first brought up in high school, I’ve simply come to terms with and embrace the fact that I’m a near perfect duplication of a young Brad Pitt:


I Can’t Choose…Really, I Can’t

In my last post, I explained a little bit of how addiction works in our brains. For addiction to occur, we must have had to have taken the addictive substance in first place, something many people, such as Peter Hitchens you may remember, regard erroneously as a choice that is worthy of punishment. Let’s look at how our brains make decisions and see if we agree with Mr. Hitchens, or if we have a different opinion. (more…)