Older news items (pre-2010) brought over from the old website
More light shed on distinction between long and short-term memory
The once clear-cut distinction between long- and short-term memory has increasingly come under fire in recent years. A new study involving patients with a specific form of epilepsy called 'temporal lobe epilepsy with bilateral hippocampal sclerosis' has now clarified the distinction. The patients, who all had severely compromised hippocampi, were asked to try and memorize photographic images depicting normal scenes. Their memory was tested and brain activity recorded after five seconds or 60 minutes. As expected, the patients could not remember the images after 60 minutes, but could distinguish seen-before images from new at five seconds. However, their memory was poor when asked to recall details about the images. Brain activity showed that short-term memory for details required the coordinated activity of a network of visual and temporal brain areas, whereas standard short-term memory drew on a different network, involving frontal and parietal regions, and independent of the hippocampus.
Cashdollar, N., Malecki, U., Rugg-Gunn, F. J., Duncan, J. S., Lavie, N., & Duzel, E. (2009). Hippocampus-dependent and -independent theta-networks of active maintenance. Proceedings of the National Academy of Sciences, 106(48), 20493-20498. doi: 10.1073/pnas.0904823106.
Why smells can be so memorable
Confirming the common experience of the strength with which certain smells can evoke emotions or memories, an imaging study has found that, when people were presented with a visual object together with one, and later with a second, set of pleasant and unpleasant odors and sounds, then presented with the same objects a week later, there was unique activation in particular brain regions in the case of their first olfactory (but not auditory) associations. This unique signature existed in the hippocampus regardless of how strong the memory was — that is, it was specific to olfactory associations. Regardless of whether they were smelled or heard, people remembered early associations more clearly when they were unpleasant.
The study appeared online on November 5 in Current Biology.
Two studies help explain the spacing effect
I talked about the spacing effect in my last newsletter. Now it seems we can point to the neurology that produces it. Not only that, but the study has found a way of modifying it, to improve learning. It’s a protein called SHP-2 phosphatase that controls the spacing effect by determining how long resting intervals between learning sessions need to last so that long-lasting memories can form. The discovery happened because more than 50% of those with a learning disorder called Noonan's disease have mutations in a gene called PTP11, which encodes the SHP-2 phosphatase protein. These mutations boost the activity levels of SHP-2 phosphatase, which, in genetically modified fruit flies, disturbs the spacing effect by increasing the interval before a new chemical signal can occur (it is the repeated formation and decay of these signals that produces memory). Accordingly, those with the mutation need longer periods between repetitions to establish long-term memory.
Pagani, M.R. et al. 2009. Spacing Effect: SHP-2 Phosphatase Regulates Resting Intervals Between Learning Trials in Long-Term Memory Induction. Cell, 139 (1), 186-198.
A study involving Aplysia (often used as a model for learning because of its simplicity and the large size of its neural connections) reveals that spaced and massed training lead to different types of memory formation. The changes at the synapses that underlie learning are controlled by the release of the neurotransmitter serotonin. Four to five spaced applications of serotonin generated long-term changes in the strength of the synapse and less activation of the enzyme Protein kinase C Apl II, leading to stronger connections between neurons. However, when the application of serotonin was continuous (as in massed learning), there was much more activation of PKC Apl II, suggesting that activation of this enzyme may block the mechanisms for generating long-term memory, while retaining mechanisms for short-term memory.
Villareal, G., Li, Q., Cai, D., Fink, A. E., Lim, T., Bougie, J. K., et al. (2009). Role of Protein Kinase C in the Induction and Maintenance of Serotonin-Dependent Enhancement of the Glutamate Response in Isolated Siphon Motor Neurons of Aplysia californica. J. Neurosci., 29(16), 5100-5107.
Smart gene helps brain cells communicate
For the second time, scientists have created a smarter rat by making their brains over-express CaMKII, a protein that acts as a promoter and signaling molecule for the NR2B subunit of the NMDA receptor. Over-expressing the gene lets brain cells communicate a fraction of a second longer. The research indicates that it plays a crucial role in initiating long-term potentiation. The NR2B subunit is more common in juvenile brains; after puberty the NR2A becomes more common. This is one reason why young people tend to learn and remember better — because the NR2B keeps communication between brain cells open maybe just a hundred milliseconds longer than the NR2A. Although this genetic modification is not something that could probably be replicated in humans, it does validate NR2B as a drug target for improving memory in healthy individuals as well as those struggling with Alzheimer's or mild dementia.
Wang, D., Cui, Z., Zeng, Q., Kuang, H., Wang, L. P., Tsien, J. Z., et al. (2009). Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats. PLoS ONE, 4(10), e7486.
Full text at http://dx.plos.org/10.1371/journal.pone.0007486
Concepts are born in the hippocampus
Concepts are at the heart of cognition. A study showed 25 people pairs of fractal patterns that represented the night sky and asked them to forecast the weather – either rain or sun – based on the patterns. The task could be achieved by either working out the conceptual principles, or simply memorizing which patterns produced which effects. However, the next task required them to make predictions using new patterns (but based on the same principles). Success on this task was predictable from the degree of activity in the hippocampus during the first, learning, phase. In the second phase, the ventromedial prefrontal cortex, important in decision-making, was active. The results indicate that concepts are learned and stored in the hippocampus, and then passed on to the vMPFC for application.
Kumaran, D. et al. 2009. Tracking the Emergence of Conceptual Knowledge during Human Decision Making. Neuron, 63 (6), 889-901.
Why we learn more from our successes than our failures
A monkey study shows for the first time how single cells in the prefrontal cortex and basal ganglia change their responses as a result of information about what is the right action and what is the wrong one. Importantly, when a behavior was successful, cells became more finely tuned to what the animal was learning — but after a failure, there was little or no change in the brain, and no improvement in behavior. The finding points to the importance of successful actions in learning new associations.
Histed, M.H., Pasupathy, A. & Miller, E.K. 2009. Learning Substrates in the Primate Prefrontal Cortex and Striatum: Sustained Activity Related to Successful Actions. Neuron, 63 (2), 244-253.
New insight into how information is encoded in the hippocampus
Theta brain waves are known to orchestrate neuronal activity in the hippocampus, and for a long time it’s been thought that these oscillations were "in sync" across the hippocampus, timing the firing of neurons like a sort of central pacemaker. A new rat study reveals that rather than being in sync, theta oscillations actually sweep along the length of the hippocampus as traveling waves. This changes our notion of how spatial information is represented in the rat brain (and presumably has implications for our brains: theta waves are ubiquitous in mammalian brains). Rather than neurons encoding points in space, it seems that what is encoded are segments of space. This would make it easier to distinguish between representations of locations from different times. It also may have significant implications for understanding how information is transmitted from the hippocampus to other areas of the brain, since different areas of the hippocampus are connected to different areas in the brain. The fact that hippocampal activity forms a traveling wave means that these target areas receive inputs from the hippocampus in a specific sequence rather than all at once.
Lubenov, E.V. & Siapas, A.G. 2009. Hippocampal theta oscillations are travelling waves. Nature, 459, 534-539.
How the brain translates memory into action
We know that the hippocampus is crucial for place learning, especially for the rapid learning of temporary events (such as where we’ve parked the car). Now a new study reveals more about how that coding for specific places connects to behaviour. Selective lesioning in rats revealed that the critical part is in the middle part of the hippocampus, where links to visuospatial information connect links to the behavioural control necessary for returning to that place after a period of time. Rats whose brain still maintained an accurate memory of place nevertheless failed to find their way when a sufficient proportion of the intermediate hippocampus was removed. The findings emphasise that memory failures are not only, or always, about actual deficits in memory, but can also be about being able to act on it.
Bast, T. et al. 2009. From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus. PLoS Biology, 7(4), e1000089.
How what we like defines what we know
How we categorize items is crucial to both how we perceive them and how well we remember them. Expertise in a subject is a well-established factor in categorization — experts create more specific categories. Because experts usually enjoy their areas of expertise, and because time spent on a subject should result in finer categorization, we would expect positive feelings towards an item to result in more specific categories. However, research has found that positive feelings usually result in more global processing. A new study has found that preference does indeed result in finer categorization and, more surprisingly, that this is independent of expertise. It seems that preference itself activates focused thinking that directly targets the preferred object, enabling more detailed perception and finer categorization.
Smallman, R. & Roese, N.J. 2008. Preference Invites Categorization. Psychological Science, 19 (12).
Encoding isn’t solely in the hippocampus
Perhaps we can improve memory in older adults with a simple memory trick. The hippocampus is a vital region for learning and memory, and indeed the association of related details to form a complete memory has been thought to occur entirely within this region. However, a new imaging study has found that when volunteers memorized pairs of words such as "motor/bear" as new compound words ("motorbear") rather than separate words, then the perirhinal cortex, rather than the hippocampus, was activated, and this activity predicted whether the volunteers would be able to successfully remember the pairs in the future.
Haskins, A.L. et al. 2008. Perirhinal Cortex Supports Encoding and Familiarity-Based Recognition of Novel Associations. Neuron, 59, 554-560.
Computer model reveals how brain represents meaning
A new computational model has been developed that can predict with 77% accuracy which areas of the brain are activated when a person thinks about a specific concrete noun. The success of the model points to a new understanding of how our brains represent meaning. The model was constructed on the basis of the frequency with which a noun co-occurs in text (from a trillion-word text corpus) with each of 25 verbs associated with sensory-motor functions, including see, hear, listen, taste, smell, eat, push, drive and lift. These 25 verbs appear to be basic building blocks the brain uses for representing meaning. The effect of each co-occurrence on the activation of each tiny voxel in an fMRI brain scan was established, and from this data, activation patterns were drawn.
Mitchell, T.M. et al. 2008. Predicting Human Brain Activity Associated with the Meanings of Nouns. Science, 320 (5880), 1191-1195.
Novel mechanism for long-term learning identified
There has always been a paradox at the heart of learning: repetition is vital, yet at the level of individual synapses, repetitive stimulation might actually reverse early gains in synaptic strength. Now the mechanism that resolves this apparent paradox has been uncovered. N-methyl-D-aspartate (NMDA) receptors appear from studies to be required for the synaptic strengthening that occurs during learning, but these receptors undergo a sort of Jekyll-and-Hyde transition after the initial phase of learning. Instead of helping synapses get stronger, they actually begin to weaken the synapses and impair further learning. The new study reveals that while the NMDA receptor is required to begin neural strengthening, a second neurotransmitter receptor — the metabotropic glutamate (mGlu) receptor — then comes into play. Using an NMDA antagonist to block NMDA receptors after the initiation of plasticity resulted in enhanced synaptic strengthening, while blocking mGlu receptors caused strengthening to stop.
Clem, R.L., Celikel, T. & Barth, A.L. 2008. Ongoing in Vivo Experience Triggers Synaptic Metaplasticity in the Neocortex. Science, 319 (5859), 101-104.
Brain protein that's a personal trainer for your memory
A brain protein called kalirin has been shown to be critical for helping you learn and remember what you learned. When you learn something new, kalirin makes the synaptic spines on your neurons grow bigger and stronger the more you repeat the lesson. This may help explain why continued intellectual activity and learning delays cognitive decline as people grow older. "It's important to keep learning so your synapses stay healthy." Previous studies have found that kalirin levels are reduced in brains of people with diseases like Alzheimer's and schizophrenia. This latest finding suggests it may be a useful target for future drug therapy for these diseases.
Xie, Z. et al . 2007. Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines. Neuron, 56, 640-656.
Why learning takes a while
New findings about how new connections are made between brain cells sheds light on why it sometimes takes a little while before we truly ‘get’ something. It seems that, although connections are made within minutes, it takes eight hours before these connections are mature enough to transmit information, and more hours before the connections are firmly enough established to become fully functional synapses, likely to survive. It was also found that when a new spine made contact with a site already hosting a contact, the new spine was highly likely to displace the old connection. This may mean that newly learned information might lead to a fading of older information.
Nägerl, U.V., Köstinger, G., Anderson, J.C., Martin, A.C. & Bonhoeffer, T. 2007. Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons. The Journal of Neuroscience, 27, 8149-8156.
How memory networks are formed
We know that memories are encoded in a network of neurons, but how do the neurons “decide” which ones to connect to? A mouse study reveals that the level of a protein called CREB is critical in this decision. The findings suggest a competitivemodel in which eligible neurons are selected to participate in a memory trace as a function of their relative CREB activity at the time of learning.
Han, J-H et al. 2007. Neuronal Competition and Selection During Memory Formation. Science, 316 (5823), 457-460.
Support for labeling as an aid to memory
A study involving an amnesia-inducing drug has shed light on how we form new memories. Participants in the study participants viewed words, photographs of faces and landscapes, and abstract pictures one at a time on a computer screen. Twenty minutes later, they were shown the words and images again, one at a time. Half of the images they had seen earlier, and half were new. They were then asked whether they recognized each one. For one session they were given midazolam, a drug used to relieve anxiety during surgical procedures that also causes short-term anterograde amnesia, and for one session they were given a placebo.
It was found that the participants' memory while in the placebo condition was best for words, but the worst for abstract images. Midazolam impaired the recognition of words the most, impaired memory for the photos less, and impaired recognition of abstract pictures hardly at all. The finding reinforces the idea that the ability to recollect depends on the ability to link the stimulus to a context, and that unitization increases the chances of this linking occurring. While the words were very concrete and therefore easy to link to the experimental context, the photographs were of unknown people and unknown places and thus hard to distinctively label. The abstract images were also unfamiliar and not unitized into something that could be described with a single word.
Reder, L.M. et al. 2006. Drug-Induced Amnesia Hurts Recognition, but Only for Memories That Can Be Unitized. Psychological Science, 17(7), 562-
Why motivation helps memory
An imaging study has identified the brain region involved in anticipating rewards — specific brain structures in the mesolimbic region involved in the processing of emotions — and revealed how this reward center promotes memory formation. Cues to high-reward scenes that were later remembered activated the reward areas of the mesolimbic region as well as the hippocampus. Anticipatory activation also suggests that the brain actually prepares in advance to filter incoming information rather than simply reacting to the world.
Adcock, R.A., Thangavel, A., Knutson, B., Whitfield-Gabrieli, S. & Gabrieli, J.D.E. 2006. Reward-Motivated Learning: Mesolimbic Activation Precedes Memory Formation. Neuron, 50, 507–517.
New view of hippocampus’s role in memory
Amnesiacs have overturned the established view of the hippocampus, and of the difference between long-and short-term memories. It appears the hippocampus is just as important for retrieving certain types of short-term memories as it is for long-term memories. The critical thing is not the age of the memory, but the requirement to form connections between pieces of information to create a coherent episode. The researchers suggest that, for the brain, the distinction between 'long-term' memory and 'short-term' memory are less relevant than that between ‘feature’ memory and ‘conjunction’ memory — the ability to remember specific things versus how they are related. The hippocampus may be thought of as the brain's switchboard, piecing individual bits of information together in context.
Olson, I.R., Page, K., Moore, K.S., Chatterjee, A. & Verfaellie, M. 2006. Working Memory for Conjunctions Relies on the Medial Temporal Lobe. Journal of Neuroscience, 26, 4596 – 4601.
Priming the brain for learning
A new study has revealed that how successfully you form memories depends on your frame of mind beforehand. If your brain is primed to receive information, you will have less trouble recalling it later. Moreover, researchers could predict how likely the participant was to remember a word by observing brain activity immediately prior to presentation of the word.
Otten, L.J., Quayle, A.H., Akram, S., Ditewig, T.A. &Rugg, M.D. 2006. Brain activity before an event predicts later recollection. Nature, published online ahead of print 26February2006
A single memory is processed in three separate parts of the brain
A rat study has demonstrated that a single experience is indeed processed differently in separate parts of the brain. They found that when the rats were confined in a dark compartment of a familiar box and given a mild shock, the hippocampus was involved in processing memory for context, while the anterior cingulate cortex was responsible for retaining memories involving unpleasant stimuli, and the amygdala consolidated memories more broadly and influenced the storage of both contextual and unpleasant information.
Malin, E.L. & McGaugh, J.L. 2006. Differential involvement of the hippocampus, anterior cingulate cortex, and basolateral amygdala in memory for context and footshock. Proceedings of the National Academy of Sciences, 103 (6), 1959-1963.
Resting after new learning may not be laziness
In an intriguing rat study, researchers recorded brain activity while rats ran up and down a straight 1.5-metre run. As the rats ran along the track, the nerve cells fired in a very specific sequence. But to the researchers’ surprise, when the rats were resting, the same brain cells replayed the sequence of electrical firing over and over, but in reverse and speeded up. This is similar to the replay that occurs during sleep and consolidates spatial memory, but the reverse aspect has not been seen before, and is presumed to have something to do with reinforcing the sequence. The researchers suggest this may have general implications.
Foster, D.J. & Wilson, M.A. 2006. Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature, advance online publication; published online 12 February 2006
Protein that controls how neurons change as a result of experience
Two different research teams have identified a master protein that sheds light on one of neurobiology's biggest mysteries-how neurons change as a result of individual experiences. The protein, myocyte enhancer factor 2 (MEF2), turns on and off genes that control dendritic remodeling, that is the growth and pruning of neurons. In addition, one of the teams has identified how MEF2 switches from one program to the other, that is, from dendrite-promoting to dendrite-pruning, and the researchers have identified some of MEF2's targets. It’s suggested the MEF2 pathway could play a role in autism and other neurodevelopmental diseases, and this discovery could lead to new therapies for a host of diseases in which synapses either fail to form or run rampant.
Flavell, S.W. et al. 2006. Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number. Science, 311(5763), 1008-1012. Shalizi, A. et al. 2006. A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation. Science, 311(5763), 1012-1017.
Concrete evidence of the 'memory code'
I’m always talking about the “memory code”, and its existence is central to theories of memory, but now, for the first time, researchers have found concrete evidence of it. The coding system was discovered during an investigation into how the primary auditory cortex responds to different sounds. Rats were trained with various tones; it was found that the more important the tone, the greater the area of auditory cortex that became tuned to it — in other words, more neurons were involved in storing the information.
Rutkowski, R.G. & Weinberger, N.M. 2005. Encoding of learned importance of sound by magnitude of representational area in primary auditory cortex. Proceedings of the National Academy of Sciences, 102 (38), 13664-13669.
Seeing the formation of a memory
An optical imaging technique has enabled researchers to visualize changes in nerve connections. The study used genetically modified fruit flies, whose neuronal connections become fluorescent during synaptic transmission. The flies were conditioned to associate a brief puff of an odor with a shock. Using a high-powered microscope to watch the fluorescent signals in flies' brains as they learned, the researchers discovered that a specific set of neurons (projection neurons), had a greater number of active connections with other neurons after the conditioning experiment. These newly active connections appeared within 3 minutes after the experiment, suggesting that the synapses which became active after the learning took place were already formed but remained "silent" until they were needed to represent the new memory. The new synaptic activity disappeared by 7 minutes after the experiment, but the flies continued to avoid the odor they associated with the shock. The study suggests that the earliest representation of a new memory occurs by rapid changes – "like flipping a switch" – in the number of neuronal connections that respond to the odor, rather than by formation of new connections or by an increase in the number of neurons that represent an odor. The fact that the flies continued to show a learned response even after the new synaptic activity waned suggests that other memory traces found at higher levels in the brain took over to encode the memory for a longer period of time.
Yu, D., Ponomarev, A. & Davis, R.L. 2004. Altered representation of the spatial code for odors after olfactory classical conditioning: memory trace formation by synaptic recruitment. Neuron, 42 (3), 437–449.
More light shed on memory encoding
Anything we perceive contains a huge amount of sensory information. How do we decide what bits to process? New research has identified brain cells that streamline and simplify sensory information, markedly reducing the brain's workload. The study found that when monkeys were taught to remember clip art pictures, their brains reduced the level of detail by sorting the pictures into categories for recall, such as images that contained "people," "buildings," "flowers," and "animals." The categorizing cells were found in the hippocampus. As humans do, different monkeys categorized items in different ways, selecting different aspects of the same stimulus image, most likely reflecting different histories, strategies, and expectations residing within individual hippocampal networks.
Hampson, R.E., Pons, T.P., Stanford, T.R. & Deadwyler, S.A. 2004. Categorization in the monkey hippocampus: A possible mechanism for encoding information into memory. PNAS, 101, 3184-3189.