OK, so if I’ve learned one thing from the papers reviewed so far, it’s that the population of neurons active during the encoding of a new memory must be reactivated for that memory to be successfully remembered. But, does synaptic plasticity need to occur within the engram circuit for recall?
Yes.
And no. (more…)
Citations:
Ramirez, Liu et al. (2013). Creating a false memory in the hippocampus. Science, 341(6144): 387-391.
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.
Citations:
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…)
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.
5/366
This is one of those nights where this challenge got hard. Given the long NYC commute to and from Queens College, it’s always easy to read a paper, but typing up a review was pretty difficult as it was one of those hardcore grant writing days.
But, with a little over an hour to go in the day, I give you Yiu et al. (2014)
So, the last couple of posts have been examining memory traces and how the coactive cells involved in learning change their connectivity to retain information for later recall. But how do these cells become incorporated into the memory trace anyway? How do they, and not their neighbors, win the sweepstakes of cognition and get the chance to participate in an engram?
According to Yiu et al., it is their excitability. That is, those which are particularly excited at the time when sensory information hits will retain the memory.
What led the authors here were the observations that cells with increased CREB function seem to be preferentially active in memory processing and that CREB likely increases neuronal excitability. So, they manipulated lateral amygdala (LA) neurons in several ways. A) They mutated KCNQ2, a potassium channel subunit responsible for controlling neuronal excitability (in fact, it was shown that many members of a Czech family with a rare form of epilepsy had mutations in this subunit), in a small subpopulation of neurons. B) They injected CREB into a subpopulation. C) Expressed Kir2.1 in a subpopulation to decrease excitability. Then the mice were fear conditioned. They found that cells expressing CREB or the KCNQ2 mutant were much more likely than other cells to be c-fos positive upon memory retrieval, while cells with Kir2.1 were less likely. Behaviorally, animals who received excitation in their LA demonstrated enhanced fear memory.
Interestingly, the authors note that no matter the manipulation, the proportion of LA neurons allocated to the memory trace was constant across manipulations. Thus, participation in a memory trace is competitive, with the deciding factor of participation apparently being excitation at the time of trace formation. What is absolutely amazing about this paper is that it is the only paper I have ever seen in which the authors called a particular group of cells “losers.”
“…these winning neurons may also actively inhibit ‘‘loser’’ neurons.”
So, to summarize, neurons must be more electrically excited than their neighbors to be involved in a fear memory trace, which may result from their quicker activating of the local inhibitory circuits to shut down other cells.
What I’m not clear on is what exactly CREB is doing. I couldn’t tell if yes, enhancing CREB expression will excite the cells and allows them to be preferentially involved in a trace, or if perhaps excitation by other means can do so and enhanced CREB is doing something else. For instance, excitation preps the cell for trace incorporation in a number of ways including inducing CREB, which in and of itself isn’t the cause of preferential activation, but allows the cell to more quickly undergo LTP.
Of course, that is all exhausted speculation. Will certainly revisit this paper at a more alert time.
Goodnight.
4/344
Citations:
Garner et al. (2012). Generation of a synthetic memory trace. Science, 35(6075): 1513-1516
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…)
Nervous Talk 