Saturday, March 19, 2011

Memory on my mind

Memory storage in the brain happens simultaneously in the hippocampus and cortex.

Despite the continuing hold that supernaturalism, soul-ism, and related theistic sentiments have over much of the population, to those scientists working on the mind and consciousness, its physical nature is obvious and underpins a rich program of research.

One key to consciousness, of course, is memory, which, along with direct sensation, emotion, and whatever else bubbles up from unconscious processes, make up its contents. Sensations as well are now understood not as mechanical readings of outside input, but as template-filling exercises strongly structured by our prior experience and expectations- i.e., our memories. And emotions are increasingly characterized to have complex hormonal and anatomical sources within the brain, also strongly tied to memories, many of which are themselves unconscious.

For instance, in the paper under review this week, rats learn about what is good to eat or not by smelling the breath of another rat who has just eaten that food. Give one rat some tasty, aromatic cinnamon, and its housemates rapidly learn about it as well, and remember that goodness (if that is what the first rat thought about it) for the rest of their lives. We are all each other's taste testers, apparently!

Memory formation is currently theorized to begin in the hippocampus as short-term storage, before being deposited in the cortex for long-term storage. This model arose from studies of humans and other animals with lesions indicating that if the hippocampus is absent or disconnected, no memories form at all, while if its connections to the cortex are severed, no long-term memories are formed, though prior long-term memories are retained and short-term memories form briefly (weeks to months) as well. Some forms of immediate short term, or working, memory (like recalling phone numbers and word lists) escape this effect and are not dependent on the hippocampus at all.

The transfer mechanism between the hippocampus and the cortex is currently believed to involve sleep and dreaming, where memories are replayed, perhaps in substantially speeded-up form, reinforcing their connections and salience in the cortex.
"Replay of encoding-related activity during phases of sleep has emerged as a core mechanism for driving the structural changes within the hippocampal-cortical neuronal networks."
And what is the ultimate physical engram of memory? This is thought to be the neuronal synapse, whose structure is plastic over long and short time spans, and whose structure / connection is reinforced by electrical activity in the basic Hebbian learning hypothesis. This current paper also engages in some molecular wizardry to manipulate synaptic structural change and thence either enhance or cancel memory formation in rats.

The interesting finding in this paper is that cortical involvement is key for this type of memory in rats from the very start, not just after some weeks of residence in the hippocampus, as the prior theory had it. To figure this out the experimenters used a somewhat shocking technique of injecting the respective areas of the rat's brains with an inhibitor of synaptic transmission (CNQX) for various windows of time. So, if they blocked the hippocampus at the start of the 30-day period, no memory of the food smell occurred at the end. Conversely, if they blocked the frontal cortex in the second half of the 30-day period, the memory was reduced by half. Some key experiments are diagrammed below:

Direct brain injection of a synaptic transmission inhibitor (red) vs control fluid (gray) into the orbital frontal cortex at the time of learning (day 0) eliminates long-term memory (30 days) of the social food interaction (this time with cumin), but not the short-term memory (7 days).
Double learning test, where one inhibitor injection eliminates memory of the taste learned simultaneous with drug, but not the one learned a week beforehand.

What they found was that blocking nerve transmission in the frontal cortex during the early time (days 0 to 12) also dropped memory formation by half at the end of 30 days. They claim from this that the hippocampal-first model of memory formation may be incomplete, and perhaps nascent cortical memory is laid down at the very start, during or after the original experience, but requires reinforcement over the ensuing weeks from the hippocampus to become a long-term memory.
"This finding identifies early cortical tagging as a potentially critical process reponsible for the progressive embedding of enduring memories within cortical networks."
The experimenters supported their theories on the cellular and molecular levels by mapping synaptic morphology and numbers, intracellular golgi complex concentrations, and histone modifications in among  neurons otherwise tagged as active in the dissected rat brains, all of which are known to correlate with memory formation. They claim that the single learning trial (of 30 minutes) conducted in each experiment significantly increased measurements of these indexes in their rat's brains. Which perhaps goes to show that these rats, housed in individual plexiglass cages, were leading stultifyingly boring lives otherwise!

In addition, they applied drugs locally into the cortex that are known to alter memory formation at the cellular level, (either inhibiting or activating histone modification enzymes) at selected times; in this case at the same time as the learning session. Memories established by the social food preference learning exercise could be eradicated (or enhanced) by this pharmacological intervention, showing that while the hippocampus is sufficient for memory recall at early times (1 to 2 weeks), memory formation in the cortex depends not only on late events, but early ones as well.

Test of memory enhancement with sodium butyrate (inhibitor of histone deacetylases). Injection into the orbital frontal cortex at the time of learning significantly enhances the same type of memory that the synaptic inhibitor eliminated, thirty days later.
The main message I took from this is that the study of memory is getting remarkably detailed. Theories are becomming more refined, spanning from the behavioral and anatomical to the molecular levels, and are tested with more intricate and bizarre methods. The results are consistent with mechanistic theories of memory storage and retrieval, while being disputed and adjusted in many details as experiments go on. It is amazing, really to see this progress.

One has to ask, however, what goes on in rats getting cortical infusions of a synapse blocking agent? Were they conscious? Were they even alive? Apparently so, but these methods seem rather extreme and prone to a lot of unintended consequences. The methods section of this paper reiterates that the drugs were precisely delivered in quite small amounts. And their location and activity were verified on autopsy by staining the brains for gene expression patterns characteristic of neural and synapse activity.

In the end, a great deal remains unknown. Assuming that the Hebbian model is basically correct, how are the network engrams (i.e. memories) called up at will? Does any associating thought or sensation lead the brain to re-animate the stored memory, injecting into the stream of active thoughts? Does calling it up automatically reinforce it, or does something else have to happen, like new cognitive or emotional associations? What is the form of sleep/dream replay that reinforces memory between the hippocampus and the cortex? And of course, how do memories relate to consciousness- do they "enter" it, or do they constitute it?

  • Basic brain anatomy video.
  • Nuclear disaster, or climate disaster?
  • We need a Tobin tax, and not just on currency speculation.
  • Are scientists ready to take over the mantle of spirituality in the West?
  • Bill Mitchell ... Writes a fine piece in the Nation.
"Under the gold standard governments had to borrow to spend more than their tax revenue. But since 1971 that necessity has lapsed. Now governments issue debt to match their deficits only as a result of pressure placed on them by neoliberals to restrict their spending. Conservatives know that rising public debt can be politically manipulated and demonized, and they do this to put a brake on government spending. But there is no operational necessity to issue debt in a fiat monetary system. Interestingly, conservatives are schizoid on the question of public debt: public borrowing provides corporate welfare in the form of risk-free income flows to the rich because it allows them to safely park funds in bonds during uncertain times and provides a risk-free benchmark on which to price other, riskier financial products."


  1. I have long been curious about memory and enjoyed your post. Was wondering if you would consider a post explaining the connectome project in the most simple terms possible and your take on why it is being conducted.

    btw, your blog disappeared for a while and I went into a panic as I look forward to it every week. Glad you're back.

  2. Thanks, Silver!

    The blog has been consistent from my end. Not sure what else may have happened. Unless I blacked out for a week!

    The connectome project seems like a very good adjunct to neuroanatomy generally. I am not a neuroscientist, really, so I am not expert in the field or really congnizant of what they are trying to do, other than provide further detail to the anatomy that is so important. What really excites me are studies of brain waves and coordinated transmission patterns, al la Buzsaki. The map of the roadways is one ingredient, but how those roadways are used to create consciousness and thoughts generally.. that seems even more mysterious right now- a deep and, I think very exciting problem.

    Nevertheless, the connectome project is being done due to new technical possibilities. One of which is a lot of sectioning of brains for anatomy projects generally. The other is the special MRI technique of tensor imaging, which tracks specifically the white matter- the myelinated bundles of nerves that are the longer-range transmission conduits. This has led to some very impressive imagery of how the various regions of the brain connect.

    I see on the wiki page, they talk about "parcellation". I have my doubts about this as an idea, since brain functions are pretty plastic and small areas can be repurposed on the fly after someone has loses, say, a finger, other sensory and motor areas invade those previously used by that finger. But one very important element of the connectome, beyond its final architecture and how that supports normal thought, is how it (and the brain generally) develops from nothing.. how genes direct what is going on, what selective, pruning, and migration processes are going on, and how active input from the outside is critical to putting everything in place in a "normal" sense.

    I doubt I will blog about this in any particular way, though it has come up in the past once or twice. I wouldn't say that it is analogous to the genome which has a good deal more fundamental significance- it is a mapping project, like finding how kidneys are organized, what genes are on in the fly embryo, or how the internet is organized, etc..