the grid cells re-scale along the dorsal-ventral axis of the medial entorhinal cortex. smaller grids at the top.. it's suggested that the overlay of these grids provides a unique location, producing place cells.. so that's one part of the solution..  
 
another thing is that there is a lot of theorizng about the role of the different subregions in determining which map.. maybe we'll do that next.. in broad terms the dentate gyrus gets the information first and acts as a pattern separator/sparse coder.. the CA3 is recurrent network and then pattern completes if it can.. and the CA1 can act as a comparator/novely detector..  
 
these are some ideas.. together they might allow unique non-confusing coding..

you said it! i almost did a run through on the water maze and blind rats as well, but i fear tedium.. also have to constantly suppress the desire to try to teach people 20-30 new terms by putting their definitons in parentheses.. thanks for the input..

nice catch Fly!

yeah.. i think it was p40-MAPK an hour after conditioning.. arc seems to me to be a less memory-encoding specific gene.. more of an overall activity marker right now in my view.. even though it has some nice properties that could make it input-specific. 
 
orientation i think refers to the overall direction of axonal and dendritic branching.. for instance, in one illustrated neuron, the branches seemed to curl down in the ventral direction..

i just read it.. i have to think for a little while how their technique improves on FRAP (fluorescence recovery after photobleaching).. also there is an experiment where they use an NMDA receptor antagonist and it alters Kv1.1 production.. i'm not sure it goes the way it should though... i'm not sure how to predict which way it should go though because activating NMDARs can drive plasticity in the same way as deactivating them does sometimes.. (like in Sutton and Schuman's synaptic scaling experiments..) i guess they had an AMPAR blocker there too.. 
 
anyway. the broader importance of the paper relates to the subject of this Sutton and Schuman review that came out in cell yesterday, so maybe i'll make time to do a MEGAPOST!! on it and why local protein synthesis is important and all that.

What is the relationship between a cortical minicolumn and the long processes of the radial glia cell? One-to-one? 
From here: 
Despite the lack of conclusive evidence, most researchers believe that ontogenetic cell columns develop into adult minicolumns (Swindale, 1990; Mountcastle, 1997). A qualitative anatomical study of development in human auditory cortex concluded that ontogenetic radial cell columns were the same vertical minicolumns found in the adult brain (Krmpotic-Nemanic et al., 1984). Yuste and colleagues traced physiological activity that was columnar and radial during the development of the rat neocortex. They concluded that: ?The shape of the coronal domains strongly suggests the columnar units of visual and somatosensory cortex and the proposed radial units associated with radial glial fibers? (Yuste et al., 1992). 
 
more later.. that process growth question was a doozy.. had to go all the way back to neuroepithelial cells.. still learning.

don delillo hits this pretty hard in 'white noise'.. guy invents a pill that removes fear of death.. goes crazy and watches too much tv i think.. i can't remember.. i think he gets shot.. ah thank you sparknotes.. 
 
dylar is the anti-fear of death drug.. i should rap about that.. 
 
i see through fake emcees made of mylar 
stressed out shakin in boots droppin dylar 
depressed now no bdnf now messin round 
not a lotta product migrating to the hilar

Fly- 
there was another case of passing a molecular compound coming from miRNAs in the sperm.. i haven't read it. abstract: 
http://www.nature.com/nature/journal/v441/n7092/abs/nature04674.html 
Paramutation is a heritable epigenetic modification induced in plants by cross-talk between allelic loci. Here we report a similar modification of the mouse Kit gene in the progeny of heterozygotes with the null mutant Kittm1Alf (a lacZ insertion). In spite of a homozygous wild-type genotype, their offspring maintain, to a variable extent, the white spots characteristic of Kit mutant animals. Efficiently inherited from either male or female parents, the modified phenotype results from a decrease in Kit messenger RNA levels with the accumulation of non-polyadenylated RNA molecules of abnormal sizes. Sustained transcriptional activity at the postmeiotic stages?at which time the gene is normally silent?leads to the accumulation of RNA in spermatozoa. Microinjection into fertilized eggs either of total RNA from Kittm1Alf/+ heterozygotes or of Kit-specific microRNAs induced a heritable white tail phenotype. Our results identify an unexpected mode of epigenetic inheritance associated with the zygotic transfer of RNA molecules. 
 
no miRNAs and siRNAs are still ostensibly different.. one of the major differences is that miRNAs are transcribed from endogenous loci in a sterotypical precursor form- pri-miRNAs. i described it in more detail in my RNAi fundamentals post.. 
 
the microRNA reference was to a particular section in the Cell Arabidopsis paper.. 
 
Previous evidence suggested that microRNAs might recruit DNA methylation enzymes to their target genes (Bao et al., 2004). However, we found that annealing sites in microRNA target genes were methylated at a level slightly below the genome average (22 of 136, ?16.2%) (see Figure S4 for PHB as an example). In addition, we found that only one (MIR416a) of the 103 microRNA precursor genes was methylated. For trans-acting siRNAs (tasiRNAs) (Allen et al., 2005; Peragine et al., 2004; Vazquez et al., 2004), we found that 2 of the 5 tasiRNA-generating loci (TAS1b and TAS3) and 7 of 9 tasiRNA target sites contained methylation. However, bisulfite sequencing of the methylated tasiRNA target sites in ARF3 revealed CG methylation but an absence of non-CG methylation, which is a hallmark of RNA-directed DNA methylation (Figure S8) (Chan et al., 2005). Furthermore, DNA methylation persisted in the dcl2 dcl3 dcl4 triple mutant that lacks detectable tasiRNAs (Henderson et al., 2006). Overall, these results do not support a general role for miRNAs or tasiRNAs in the active targeting of DNA methylation. 
 
don't ask me how tasiRNA works.. this is the first time i've seen it.. i've heard of rasiRNA and that is supposed to use some of the same machinery as siRNA, but haven't had time to catch up on that either..

3) heritable stuff that doesn't depend on DNA sequence that also doesn't necessarily depend on DNA methylation or chromatin modificaiton or any change really necessarily close to the genome. 
 
this was the one i was concerned about people getting mixed up with because i have come across it in the news. friends have asked me what i think about 'epigenetics' and they are referring to this smoking and obesity study (news article): 
Scientific evidence suggests that this environmentally triggered gene expression, or epigenetic imprint, might have repercussions far beyond the immediate host body. This could explain why underweight babies born to malnourished Dutch women during World War II grew up to give birth to underweight children decades after the war and food rationing had ended. Recent studies have demonstrated that the sons of men who began smoking before reaching puberty were more prone to obesity. Clearly, the epigenetic change that took place in both original groups of parents had lastingly adverse effects on subsequent generations. "The trick," says Szyf, "is to be able to control what you activate and deactivate." 
... 
In a country propping up an increasingly fragile health care system, epigenetics may force politicians to rethink their economics. Although the field is still developing, evidence is being accumulated that points to the fact that a variety of diverse social and environmental factors such as nutrition, pollutants, housing and childcare will have a significant impact on the health of Canadians now and in the generations to come. "If we really want to strengthen our economy and the health and performance of the individuals within that economy, then we need to focus on early development and the quality of family life," says Meaney.I'm not sure what Meaney studies, but I think it might be developmental biology instead of epigenetics. It seems that in this instance the term 'epigenetic' is simply referring to any correlation between some factor in the parents' environment and the offspring outcome. This article is politicizing the term and paying lip service to the molecular definition while divorcing the concept. i can't find the smoking and obesity study right now, but i think i may have seen it in the past and i'm not sure they hypothesized any explicit mechanism for their effect. did they measure the obese children's methylation state at the 'smoking parental imprinting site' or something? 
 
i'm not very good at sociodynamics, so if anybody else wants to step up to the plate for that be my guest. 
 
as far as making the cells sit up and play tricks and converting them to stem cells, that does seem to be a focus in this area of research.  
Epigenetic reprogramming in mammals. 
 
* Morgan HD, 
* Santos F, 
* Green K, 
* Dean W, 
* Reik W. 
 
Laboratory of Developm
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2) gene activity states that do not depend on the DNA sequence. 
 
here's the example i am familiar with. maybe this has only happened in the field of learning and memory: 
Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation 
J.M. Levenson and J.D. Sweatt 
In this review we address the idea that conservation of epigenetic mechanisms for information storage represents a unifying model in biology, with epigenetic mechanisms being utilized for cellular memory at levels from behavioral memory to development to cellular differentiation. Epigenetic mechanisms typically involve alterations in chromatin structure, which in turn regulate gene expression. An emerging idea is that the regulation of chromatin structure through histone acetylation and DNA methylation may mediate long-lasting behavioral change in the context of learning and memory. We find this idea fascinating because similar mechanisms are used for triggering and storing long-term ?memory? at the cellular level, for example when cells differentiate. An additional intriguing aspect of the hypothesis of a role for epigenetic mechanisms in information storage is that lifelong behavioral memory storage may involve lasting changes in the physical, three-dimensional structure of DNA itself. 
When I read this I feel like I really must be missing something because these guys have basically written this same review twice and Nature Reviews thought it was a good idea, but to me it looks like they could have said: "We think that genes have to be regulated. Probably after memories are formed genes in neurons are regulated." The problem is that this is nothing special and I'm not sure it is 'epigenetic'. Gene regulation happens all the time in response to all sorts of environmental stimuli. Most often, the mediator between stimulus and genome is a transcription factor (TF). TFs often have buddies called co-activators or co-repressors, that help them physically control a gene's activity state. For instance: 
A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes  
Marcelo A. Wood, Michelle A. Attner, Ana M.M. Oliveira, Paul K. Brindle, and Ted Abel  
Transcriptional activation is a key process required for long-term memory formation. Recently, the transcriptional coactivator CREB-binding protein (CBP) was shown to be critical for hippocampus-dependent long-term memory and hippocampal synaptic plasticity. As a coactivator with intrinsic histone acetyltransferase activity, CBP interacts with numerous transcription factors and contains multiple functional domains...... 
Histone acetylation is one of three or four major 'epigenetic modifications' in Levenson and Sweatt's view, but it looks to me like it should be called chromatin modification, drop the ?misuse? of the term 'epigenetic', and stop acting like they ha
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Dick - 
I'll try to give you an idea of what I am talking about, but my thinking isn't entriely crystal clear, so bear with me. It seems like there are three partially overlapping phenomena that people refer to as 'epigenetic'. 
 
1) inherited gene activity states that do not depend on the DNA sequence. for instance, there are some genes that dads would like expressed in developing embryos and that moms would not like expressed and vice versa. if a moms do not like the gene they will methylate the heck out of the DNA in and around its sequence particularly in eggs. so any chromosome that comes from a female will have that gene turned off, so at best a developing embryo can only get a single dose of that gene from its dad.  
 
i am paraphrasing this, but my paraphrase may be less clear than the original passage: 
Another example of epigenetic inheritance, discovered about 15 years ago in mammals, is parental imprinting. In parental imprinting, certain autosomal genes have seemingly unusual inheritance patterns. For example, the mouse Igf2 gene is expressed in a mouse only if it was inherited from the mouse?s father. It is said to be maternally imprinted, inasmuch as a copy of the gene derived from the mother is inactive. Conversely, the mouse H19 gene is expressed only if it was inherited from the mother; H19 is paternally imprinted. The consequence of parental imprinting is that imprinted genes are expressed as if they were hemizygous, even though there are two copies of each of these autosomal genes in each cell. Furthermore, when these genes are examined at the molecular level, no changes in their DNA sequences are observed. Rather, the only changes that are seen are extra methyl (?CH3) groups present on certain bases of the DNA of the imprinted genes. Occasional bases of the DNA of most higher organisms are methylated (an exception being Drosophila). These methyl groups are enzymatically added and removed, through the action of special methylases and demethylases. The level of methylation generally correlates with the transcriptional state of a gene: active genes are less methylated than inactive genes. However, whether altered levels of DNA methylation cause epigenetic changes in gene activity or whether altered methylation levels arise as a consequence of such changes is unknown. 
the news from that Cell paper i cited is that it matters which segment of the DNA sequence is methylated. methylation in the actual coding sequence of the gene seems to be associated with the gene being in an active state (not silenced), whereas when the methylation occurs in the regulatory region where factors that modulate the gene's activity level usually bind (the promoter) the gene is likely to be silenced. reading this, the simplistic prediction is that you are better off looking in the promoter region of gene's whose activity level seems determined by which parent they were inherited from rather
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how closely could one predict a skin color from genotype at this point? i thought there was something in the archives about there being only 4 or 5 pigmentation genes.. 
http://www.gnxp.com/blog/2005/12/race-is-skin-deep.php 
what connection am i not making?

this is why 
http://scienceblogs.com/clock/2006/08/books_coming_to_life_by_christ.php

actually i just looked over the developmental paper i was thinkin of and for the most part it ignores pkm zeta in favor of pkc zeta..  
 
fly- it seems unlikely to me that people would understand the brain well enough to do what you suggested AND maintain a belief in a soul and religion and whatnot. also, whether this technique could be applied with any specificity is up for grabs..

PKMz affect anything else? 
dunno.. there is a paper looking at the expression patterns of PKC isoforms that says Zeta has highly specific profile.. also, the function is conserved since drosophila version acts similarly. interestingly, drosophila seem to maybe have two parallel memory systems (anaesthesia-sensitive and -resistant) and zeta works in the resistant portion along with a gene called radish.. unfortunately this system is less well understood and mapped than the anesthesia-sensitive system..

germane dinosaur comic?

no fair bringing up newer, better studies! looks like they at least separated things by gross brain anatomy here. 
 
The paper I wrote about was purely computational and used UniGene annotation to determine where a gene was likely to be expressed. the methods really aren't that clear. unfortunately i'm no bioinformaticist, so i can't say exactly what they did wrong. 
 
i wonder if the brain-testes thing is an artifact of simply more genes being expressed in those tissues, greater research interest, and diversity of cell types within those tissues.

yeah. i don't think it's clear what the functional outcome of immature-looking spines is. in a sense, we know what the final outcome is because we know what the symptoms of fragile X syndrome are. on the other hand, the mental retardation could be caused by some other neurological malfunction and the spine morphology is more like a side-effect.  
 
if spines can't be matured you might expect it to be difficult to ever make a secure, permanent synapse. this should in principle make it difficult to learn and maintain information, but only certain types of info are affected, i think. i wonder if the same morphology phenotype is also observed in the cerebellum for instance. searching... i guess so: 
 
The fragile X-cerebellum connection. 
 
* Huber KM. 
 
Center for Basic Neuroscience, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. kimberly.huber@utsouthwestern.edu 
 
Fragile X syndrome (FXS) is an inherited form of mental retardation that results from the loss of function of the fragile X mental retardation protein (FMRP). A recent report demonstrated alterations in the structure and plasticity of synapses on cerebellar Purkinje cells in Fmr1 knockout mice, which are a model of FXS. These synaptic alterations are associated with deficits in the cerebellar learning both in the mice and humans with FXS. This work forges an important link between the FMR1 gene, altered synaptic plasticity in the cerebellum and mental retardation. 
 
so i guess one can predict global delay in establishing permanency of connection. my question then is, how do the available mechanisms left over provide any permanency? how do fragile X patients learn how to walk or eat? 
 
there must be some compensatory mechanism that is doing the job, but not quite..

ha ha.. not just yet.. transferring PhD programs.. i expect russell will show up at my door shortly therafter though..

i guess another way to say what i'm thinking is that there is no ratio of ES cell promise to AS cell promise that would allow a prolife person to accept ES cell research. so what is the point in disparaging it and the scientists who want to work on it when their principles are set regardless of this parameter.

razib, 
 
but they didn't develop an interest in adult stem cells because there is all this buzz about their medical potential. they needed something to offer in replacement for the research program they were about to demolish irrationally. irrational in my opinion, of course. 
 
its difficult to argue that this ball of cells has any sort of moral status unless one believes in ensoulment. otherwise, i tend to agree with the home depot analogy about how a pile of 2x4's does not a house make. i'm probably gonna require at least one nerve cell as a minimal requirement for 'capacity for suffering' and the beginnings of a moral claim. 
 
we shouldn't have to have the argument about whether ES Cells can cure Alzheimer's. they will advance knowledge and have some potential to help with human disease at no more cost than any other type of research. the slightest bit of pro- to a zero con- will tip the balance all the way.  
 
so now we have to have a national argument and delay research with potential so as to satisfy people who think there are ghosts floating around in their heads. i don't go out of my way to be a militant on these things, but this is a little frustrating.

my impression of Ponnuru: 
 
i could turn my steering wheel to avoid hitting this pedestrian, but i might run over an earthworm on the sidewalk.