How the Brain Works

See also



Why do we find it so hard to stay on task for long? A recent study uses a new technique to show how the task control network and the default mode network interact (and fight each other for control).

The task control network (which includes the dorsal anterior cingulate and bilateral anterior insula) regulates attention to surroundings, controlling your concentration on tasks. The default mode network, on the other hand, becomes active when a person seems to be doing 'nothing', and becomes less active when a task is being performed.

The study shows that we work better and faster the better the default mode network is suppressed by the task control network. However, when the default mode network is not sufficiently suppressed by the task control network, it sends signals to the task control network, interfering with its performance (and we lose focus).

Interestingly, in certain conditions, such as autism, depression, and mild cognitive impairment, the default mode network remains unchanged whether the person is performing a task or interacting with the environment. Additionally, deficits in the functioning of the default mode network have been implicated in age-related cognitive decline.

The findings add a new perspective to our ideas about attention. One of the ongoing questions concerns the relative importance of the two main aspects of attention: focus, and resisting distraction. A lot of work in recent years has indicated that a large part of age-related cognitive decline is a growing difficulty in resisting distraction. Similarly, there is some evidence that people with a low working memory capacity are less able to ignore irrelevant information.

This recent finding, then, suggests that these difficulties in ignoring distracting / irrelevant stimuli reflect the failure of the task control network to adequately suppress the activity of the default mode network. This puts the emphasis back on training for focus, and may help explain why meditation practices are effective in improving concentration.

[3384] Wen, X., Liu Y., Yao L., & Ding M.
(2013).  Top-Down Regulation of Default Mode Activity in Spatial Visual Attention.
The Journal of Neuroscience. 33(15), 6444 - 6453.

A new study has found that errors in perceptual decisions occurred only when there was confused sensory input, not because of any ‘noise’ or randomness in the cognitive processing. The finding, if replicated across broader contexts, will change some of our fundamental assumptions about how the brain works.

The study unusually involved both humans and rats — four young adults and 19 rats — who listened to streams of randomly timed clicks coming into both the left ear and the right ear. After listening to a stream, the subjects had to choose the side from which more clicks originated.

The errors made, by both humans and rats, were invariably when two clicks overlapped. In other words, and against previous assumptions, the errors did not occur because of any ‘noise’ in the brain processing, but only when noise occurred in the sensory input.

The researchers supposedly ruled out alternative sources of confusion, such as “noise associated with holding the stimulus in mind, or memory noise, and noise associated with a bias toward one alternative or the other.”

However, before concluding that the noise which is the major source of variability and errors in more conceptual decision-making likewise stems only from noise in the incoming input (in this case external information), I would like to see the research replicated in a broader range of scenarios. Nevertheless, it’s an intriguing finding, and if indeed, as the researchers say, “the internal mental process was perfectly noiseless. All of the imperfections came from noise in the sensory processes”, then the ramifications are quite extensive.

The findings do add weight to recent evidence that a significant cause of age-related cognitive decline is sensory loss.

[3376] Brunton, B. W., Botvinick M. M., & Brody C. D.
(2013).  Rats and Humans Can Optimally Accumulate Evidence for Decision-Making.
Science. 340(6128), 95 - 98.

Following on from research showing that long-term meditation is associated with gray matter increases across the brain, an imaging study involving 27 long-term meditators (average age 52) and 27 controls (matched by age and sex) has revealed pronounced differences in white-matter connectivity between their brains.

The differences reflect white-matter tracts in the meditators’ brains being more numerous, more dense, more myelinated, or more coherent in orientation (unfortunately the technology does not yet allow us to disentangle these) — thus, better able to quickly relay electrical signals.

While the differences were evident among major pathways throughout the brain, the greatest differences were seen within the temporal part of the superior longitudinal fasciculus (bundles of neurons connecting the front and the back of the cerebrum) in the left hemisphere; the corticospinal tract (a collection of axons that travel between the cerebral cortex of the brain and the spinal cord), and the uncinate fasciculus (connecting parts of the limbic system, such as the hippocampus and amygdala, with the frontal cortex) in both hemispheres.

These findings are consistent with the regions in which gray matter increases have been found. For example, the tSLF connects with the caudal area of the temporal lobe, the inferior temporal gyrus, and the superior temporal gyrus; the UNC connects the orbitofrontal cortex with the amygdala and hippocampal gyrus

It’s possible, of course, that those who are drawn to meditation, or who are likely to engage in it long term, have fundamentally different brains from other people. However, it is more likely (and more consistent with research showing the short-term effects of meditation) that the practice of meditation changes the brain.

The precise mechanism whereby meditation might have these effects can only be speculated. However, more broadly, we can say that meditation might induce physical changes in the brain, or it might be protecting against age-related reduction. Most likely of all, perhaps, both processes might be going on, perhaps in different regions or networks.

Regardless of the mechanism, the evidence that meditation has cognitive benefits is steadily accumulating.

The number of years the meditators had practiced ranged from 5 to 46. They reported a number of different meditation styles, including Shamatha, Vipassana and Zazen.

An experiment with congenitally deaf cats has revealed how deaf or blind people might acquire other enhanced senses. The deaf cats showed only two specific enhanced visual abilities: visual localization in the peripheral field and visual motion detection. This was associated with the parts of the auditory cortex that would normally be used to pick up peripheral and moving sound (posterior auditory cortex for localization; dorsal auditory cortex for motion detection) being switched to processing this information for vision.

This suggests that only those abilities that have a counterpart in the unused part of the brain (auditory cortex for the deaf; visual cortex for the blind) can be enhanced. The findings also point to the plasticity of the brain. (As a side-note, did you know that apparently cats are the only animal besides humans that can be born deaf?)

The findings (and their broader implications) receive support from an imaging study involving 12 blind and 12 sighted people, who carried out an auditory localization task and a tactile localization task (reporting which finger was being gently stimulated). While the visual cortex was mostly inactive when the sighted people performed these tasks, parts of the visual cortex were strongly activated in the blind. Moreover, the accuracy of the blind participants directly correlated to the strength of the activation in the spatial-processing region of the visual cortex (right middle occipital gyrus). This region was also activated in the sighted for spatial visual tasks.

Last month I reported on a finding that estrogen acts through calpain, a protein crucial to learning and memory, that acts as a neurotransmitter in the brain. Now a new study has found that BDNF activates calpain, and when it does, the spine structure changes in ways similar to those that occur during learning. When activation was blocked with calpain inhibitors, the addition of BDNF had no effect. All this implies that all the great benefits of BDNF for learning and memory are in fact due to calpain.

Older news items (pre-2010) brought over from the old website

Learning 'sculpts' the brain's connections

The ‘resting state’ of the brain is characterized by spontaneous brain activity that has not been understood. Now a new study involving 14 volunteers has found that learning a new task causes measurable changes in that activity, and the degree of change reflects how well subjects have learned to perform the task. The volunteers’ brains were scanned while they were doing nothing, during their learning of a visual task, and afterward, while they did nothing. During the task, part of the visual cortex and frontal-parietal areas involved in the control of spatial attention were particularly active. After learning the task over 5-7 days, during the ‘resting state’ each of these two regions was more likely to be active when the other region wasn't. Subjects who were more successful at the task exhibited a higher degree of this "anti-correlation".

Lewis, C. M., Baldassarre, A., Committeri, G., Romani, G. L., & Corbetta, M. (2009). Learning sculpts the spontaneous activity of the resting human brain. Proceedings of the National Academy of Sciences, 106(41), 17558-17563. doi: 10.1073/pnas.0902455106.

White matter helps brain learn

Research has concentrated on the effects of learning on gray matter, but in a new study involving 24 right-handed volunteers given 6 weeks of training in juggling, white matter was also investigated. It was found that there was not only changes in gray matter in a part of the parietal lobe associated with spatial coordination, but also the myelin in the same region appeared thicker. The gains in both were eroded after four weeks of no juggling. The findings indicate that gray matter and white matter are more interdependent than thought.

Presented at the 15th Annual Meeting of the Organization for Human Brain Mapping held in San Francisco June 18-23.

Circadian clock may be critical for remembering what you learn

We know circadian rhythm affects learning and memory in that we find it easier to learn at certain times of day than others, but now a study involving Siberian hamsters has revealed that having a functioning circadian system is in itself critical to being able to remember. The finding has implications for disorders such as Down syndrome and Alzheimer's disease. The critical factor appears to be the amount of the neurotransmitter GABA, which acts to inhibit brain activity. The circadian clock controls the daily cycle of sleep and wakefulness by inhibiting different parts of the brain by releasing GABA. It seems that if it’s not working right, if the hippocampus is overly inhibited by too much GABA, then the circuits responsible for memory storage don't function properly. The effect could be fixed by giving a GABA antagonist, which blocks GABA from binding to synapses. Recent mouse studies have also demonstrated that mice with symptoms of Down syndrome and Alzheimer's also show improved learning and memory when given the same GABA antagonist. The findings may also have implications for general age-related cognitive decline, because age brings about a degradation in the circadian system. It’s also worth noting that the hamsters' circadian systems were put out of commission by manipulating the hamsters' exposure to light, in a technique that was compared to "sending them west three time zones." The effect was independent of sleep duration.

Ruby, N.F. et al 2008. Hippocampal-dependent learning requires a functional circadian system. Proceedings of the National Academy of Sciences, 105 (40), 15593-15598.

The effect of gamma waves on cognitive and language skills in children

Gamma waves are fast, high-frequency brainwaves that spike when higher cognitive processes are engaged. Research suggests that lower levels of gamma power might hinder the brain's ability to bind thoughts together. In the first study of the "resting" gamma power in the frontal cortex in young children (16, 24 and 36 months old), it’s been revealed that those with higher language and cognitive abilities had correspondingly higher gamma power than those with poorer language and cognitive scores. Children with better attention and inhibitory control also had higher gamma power. There were no differences in gamma power based on gender or socio-economic status, but children with a family history of language impairments showed lower levels of gamma activity. The finding may enable more accurate pinpointing of a child’s development, enabling earlier, and better targeted, intervention.

Benasich, A.A. et al. 2008. Early cognitive and language skills are linked to resting frontal gamma power across the first 3 years. Behavioral Brain Research, 195 (2), 215-222.

Balance in inhibition and excitation is key to learning

A new mouse study has revealed not only the mechanism for learning deficits resulting from neurofibromatosis type 1, but also something fundamental about learning. It seems that the deficits in learning experienced by mice with an abnormal version of the Nf1 gene stem from an increased release by inhibitory neurons of the inhibitory neurotransmitter GABA. Moreover, the learning deficits can be reversed with treatments that reign GABA levels back in. The study also found show that GABA levels normally swell when mice learn, suggesting that a balance of GABA, a balance between excitatory and inhibitory signals, may be key. Changes in GABA inhibition have also recently been implicated in an animal model of Down's syndrome.

Cui, Y. et al. 2008. Neurofibromin Regulation of ERK Signaling Modulates GABA Release and Learning. Cell, 135 (3), 549-560.

Deep brain stimulation may improve memory

In a truly serendipitous and surprising development, experimental brain surgery intended to suppress an obese man's appetite using the increasingly successful technique of deep-brain stimulation, induced an intense recollection of an event from his distant past. More tests showed his ability to learn was dramatically improved when the current was switched on and his brain stimulated. Scientists are now applying the technique in the first trial of the treatment in 6 patients with Alzheimer's disease. The effect is surprising in that it involves stimulation of the hypothalamus, a critical region for metabolic regulation, but not one that has ever been associated with memory. However, the best contact was in a place close to the fornix, an arched bundle of fibres that carries signals within the limbic system, which is involved in memory and emotions and is situated next to the hypothalamus. Deep brain stimulation has been used for some time to treat Parkinson’s disease and other movement disorders.

Hamani, C. et al. 2008. Memory Enhancement Induced by Hypothalamic/Fornix Deep Brain Stimulation. Annals of Neurology, 63 (1), 119-123.

Brain's voluntary chain-of-command ruled by not 1 but 2 captains

Previous research has shown a large number of brain regions (39) that are consistently active when people prepare for a mental task. It’s been assumed that all these regions work together under the command of one single region. A new study, however, indicates that there are actually two independent networks operating. The cingulo-opercular network (including the dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex) is linked to a "sustain" signal — it turns on at the beginning, hums away constantly during the task, then turns off at the end. In contrast, the frontoparietal network (including the dorsolateral prefrontal cortex and intraparietal sulcus) is active at the start of mental tasks and during the correction of errors. The findings may help efforts to understand the effects of brain injury and develop new strategies to treat such injuries.

Dosenbach, N.U.F. et al. 2007. Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences, 104 (26), 11073-11078.

How the brain detects novelty

New research suggests that the hippocampus makes predictions of what will happen next by automatically recalling an entire sequence of events in response to a single cue, allowing us to anticipate future events and detect when things do not turn out as expected. Rather than reacting to novelty, the hippocampus seems to act as a comparison device, matching up past and present experience.

Kumaran, D. & Maguire, E.A. 2006. An unexpected sequence of events: Mismatch detection in the human hippocampus. PLoS Biol 4(12): e424. DOI: 10.1371/journal.pbio.0040424
The full text is available at

Connections between neurons act as information filters in the brain

Synapses — the connections between brain cells — have long been known to be important in information-processing, but the exact nature of their role has not been clear. Are they a crucial part of the processing itself, or simply part of the transport system? Worryingly, research has suggested that synapses drop up to 90% of all incoming signals — an unreliability difficult to reconcile with the fact that brain as a whole is very reliable. A new study has cast new light on synaptic activity. It turns out that synaptic transmission is highly temperature-dependent. Previous studies had studied isolated groups of neurons at room temperature; the present study recorded data at wormer conditions — almost body temperature. And revealed that excitatory and inhibitory synapses, previously thought to always work against each other, in fact act in concert to identify patterns carrying relevant information in an incoming signal. As a result, meaningful patterns are amplified, and stray noise is discarded. This provides the experimental confirmation needed, for the view that synapses act to filter the “noise” and makes the information processing reliable.

Klyachko,V.A. & Stevens, C.F. 2006. Excitatory and Feed-Forward Inhibitory Hippocampal Synapses Work Synergistically as an Adaptive Filter of Natural Spike Trains. PLoS Biology, 4 (7), DOI: 10.1371/journal.pbio.0040207  Full text available at:

Master planners in brain may coordinate other areas' roles in cognitive tasks

Scans of 183 subjects have identified 3 brain areas most consistently active during a variety of cognitive tasks — the dorsal anterior cingulate and the left and right frontal operculum. It’s suggested that these regions coordinate the activities of specialized regions. In a rather lovely analogy, researchers suggested that if the brain in action can be compared to a symphony, with specialized sections required to pitch in at the right time to produce the desired melody, then the regions highlighted by the new study may be likened to conductors. Until now, the function of the opercula has been a mystery; the findings also suggest a rethinking of the role of the cingulate.

Dosenbach, N.U.F. et al. 2006. A core system for the implementation of task sets. Neuron, 50(5), 799-812.

How brain cells communicate

A new finding has added to our understanding of how brain cells communicate. A protein called syndapin, previously thought to have no major role in nerve communication, has proven to be the molecule that works with a key protein called dynamin to allow the transmission of messages between nerve cells. The finding has implications for the treatment of many neurological disorders.

Anggono, V. et al. 2006. Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neuroscience, 9, 752 – 760.

New understanding of how neurons communicate

Although we knew that the release of neurotransmitters at the synapses of neurons causes the voltage inside the neuron to fluctuate continuously — an analog signal — it’s always been thought that the axon was impassable to those fluctuations, and thus that neurons can only communicate with each other through a digital code — that is, by sending out signals whose information is reading in the timing of the pulses. A new study now suggests that the analog signal can indeed travel along the axon, and that the digital signal passed between synapses is influenced by that analog signal. The discovery may lead to a better understanding of disorders such as epilepsy and migraine, both of which involve large changes in the voltage inside neurons.

Shu, Y., Hasenstaub, A., Duque, A., Yu, Y. & McCormick, D.A. 2006. Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential. Nature, advance online publication 12 April 2006.

Rating familiarity: how we do it

Previous research has indicated that recognizing a familiar object is accompanied by a reduction in activity in the medial temporal lobe. A new imaging study has confirmed the reduced activity and demonstrated that the degree of reduction is correlated with the degree of familiarity of the object (a face in this instance). The reduction began very rapidly in the recognition process. The researchers suggested that the graded response of medial temporal structures are what allows us to assess how familiar an object is.

Gonsalves, B.D., Curran, T., Norman, K.A. & Wagner, A.D. 2005. Memory Strength and Repetition Suppression: Multimodal Imaging of Medial Temporal Cortical Contributions to Recognition. Neuron, 47, 751–761.

Single cell recognition research finds specific neurons for concepts

An intriguing study surprises cognitive researchers by showing that individual neurons in the medial temporal lobe are able to recognize specific people and objects. It’s long been thought that concepts such as these require a network of cells, and this doesn’t deny that many cells are involved. However, this new study points to the importance of a single brain cell. The study of 8 epileptic subjects found variable responses from subjects, but within subjects, individuals showed remarkably specific responses to concepts. For example, a single neuron in the left posterior hippocampus of one subject responded to all pictures of actress Jennifer Aniston, and also to Lisa Kudrow, her co-star on the TV hit "Friends", but not to pictures of Jennifer Aniston together with actor Brad Pitt, and not, or only very weakly, to other famous and non-famous faces, landmarks, animals or objects. In another patient, pictures of actress Halle Berry activated a neuron in the right anterior hippocampus, as did a caricature of the actress, images of her in the lead role of the film "Catwoman," and a letter sequence spelling her name. The results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.

Quiroga, R.Q., Reddy, L., Kreiman, G., Koch, C & Fried, I. 2005. Invariant visual representation by single neurons in the human brain. Nature, 435, 1102-1107.

Brain networks change according to cognitive task

Using a newly released method to analyze functional magnetic resonance imaging, researchers have demonstrated that the interconnections between different parts of the brain are dynamic and not static. Moreover, the brain region that performs the integration of information shifts depending on the task being performed. The study involved two language tasks, in which subjects were asked to read individual words and then make a spelling or rhyming judgment. Imaging showed that the lateral temporal cortex (LTC) was active for the rhyming task, while the intraparietal sulcus (IPS) was active for the spelling task. The inferior frontal gyrus (IFG) and the fusiform gyrus (FG) were engaged by both tasks. However, Dynamic Causal Modeling (the new method for analyzing imaging data) revealed that the network took different configurations depending on the goal of the task, with each task preferentially strengthening the influences converging on the task-specific regions (LTC for rhyming, IPS for spelling). This suggests that task specific regions serve as convergence zones that integrate information from other parts of the brain. Additionally, switching between tasks led to changes in the influence of the IFG on the task-specific regions, suggesting the IFG plays a pivotal role in making task-specific regions more or less sensitive. This is consistent with previous studies showing that the IFG is active in many different language tasks and plays a role in integrating brain regions.

Bitan, T., Booth, J.R., Choy, J., Burman, D.D., Gitelman, D.R. & Mesulam, M-M. 2005. Shifts of Effective Connectivity within a Language Network during Rhyming and Spelling. Journal of Neuroscience, 25, 5397-5403.

First real-time view of developing neurons reveals surprises

New technology and a small see-through fish called a zebra fish have enabled researchers to watch individual neurons mature. Monitoring the hundreds of neurons in the region of the brain that respond to images, the researchers expected to find that young neurons fire in response to a variety of different images, then refine their role over time so that in the adult fish the neurons only respond to images moving in a certain direction or near the left or right side of the visual field. Instead they found that the neurons fired when they sensed only one type of movement as soon as the neurons were old enough to respond to the images. However, they did take time to establish stable connections. Young neurons send out branches in all directions in the hopes that some branches will connect to other neurons and form synapses that transfer information. As the neuron matures, some of these branches form stable synapses while others recede. This trial-and-error process is what establishes the final interconnected mesh of the brain.

Niell, C.M. &Smith, S.J. 2005. Functional Imaging Reveals Rapid Development of Visual Response Properties in the Zebrafish Tectum. Neuron, 45, 941-951.

Faster neuron transmission in young males

A study of 186 male and 201 female students (aged 18-25) has found that men's brain cells can transmit nerve impulses 4% faster than women's, probably due to the faster increase of white matter in the male brain during adolescence.

Reed, T.E., Vernon, P.A. & Johnson, A.M. 2005. Confirmation of correlation between brain nerve conduction velocity and intelligence level in normal adults. Intelligence, In Press, Corrected Proof, Available online 12 September 2004,5744,12170249%255E2703,00.html

New theory challenges current view of how brain stores long-term memory

The current view of long-term memory storage is that, at the molecular level, new proteins are manufactured (a process known as translation), and these newly synthesized proteins subsequently stabilize the changes underlying the memory. Thus, every new memory results in a permanent representation in the brain. A new theory of memory storage suggests instead that there is no permanent representation. Rather, memories are copied across many different brain networks. The advantage is that it is a highly flexible system, enabling rapid retrieval even of infrequent elements.
The theory suggests that the brain stores long-term memory by rapidly changing the shape of proteins already present at those synapses activated by learning. The theory explains a number of phenomena that are not properly answered by the existing theory. The theory doesn’t disagree with the view that it is the synapse that is modified in response to learning; the disagreement concerns how that synaptic modification occurs. Current theory says it is brought about by recently synthesized proteins; the new theory suggests that learning leads to a post-synthesis (post-translational) synaptic protein modification that results in changes to the shape, activity and/or location of existing synaptic proteins. It is suggested that long-term memory storage relies on a positive-feedback rehearsal system that continually updates or fine-tunes post-translational modification of previously modified synaptic proteins, thus allowing for the continual modifications of memories.

Routtenberg, A. & Rekart, J.L. 2005. Post-translational protein modification as the substrate for long-lasting memory. Trends in Neurosciences, 28 (1), 12-19.

Memory mechanism identified

Long-term memories are stored in the brain through strengthening of the connections (synapses) between neurons. Researchers have known for many years that neurons must turn on the synthesis of new proteins for long-term memory storage and synaptic strengthening to occur, but the mechanisms by which neurons accomplish these tasks have remained elusive. Now research has identified a crucial molecular pathway that allows neurons to rapidly boost their production of new proteins. The central component of this pathway, an enzyme called "mitogen-activated protein kinase" (MAPK), effectively provides a molecular switch that triggers long-term memory storage by mobilizing the protein synthesis machinery. The research also reveals that activation of MAPK increased production production of a large number of proteins. Many researchers have thought that only a very limited number of proteins are involved in long-term memory formation.

Kelleher, R.J., Govindarajan, A., Jung, H-Y., Kang, H. & Tonegawa, S. 2004. Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory. Cell, 116, 467-479.

Stages of memory clarified in sleep studies

Two new studies add to our understanding of the effects of sleep on memory. Both studies involved young adults and procedural (skill) learning, and found temporary declines in performance in particular contexts (a brief description of these studies is given here). On the basis of these studies, researchers identified three stages of memory processing: the first stage of memory — its stabilization — seems to take around six hours. During this period, the memory appears particularly vulnerable to being “lost”. The second stage of memory processing — consolidation — occurs during sleep. The third and final stage is the recall phase, when the memory is once again ready to be accessed and re-edited. (see my article on consolidation for more explanation of the processes of consolidation and re-consolidation) The surprising aspect to this is the time it appears to take for memories to initially stabilize. The studies also confirm the role of sleep in the consolidation process.

Walker, M.P., Brakefield, T., Hobson, J.A. & Stickgold, R. 2003. Dissociable stages of human memory consolidation and reconsolidation. Nature, 425, 616-620.,9865,1059138,00.html

Brain implant may restore memory

An artificial hippocampus — a programmed silicone chip — is to be linked with live tissue taken from rat brains, and then will be tested on live animals. If all goes well, it will then be tested as a way to help people who have suffered brain damage due to stroke, epilepsy or Alzheimer's disease.,3604,912940,00.html

Fear-conditioning study demonstrates long-suspected link between longterm potentiation and learning

It has long been felt that learning and memory must require physical changes in neurons that increase their responsivity to other neurons, so that they will continue to respond in the long-term even in the absence of external stimuli. Until now, however, noone has been able to actually demonstrate that this long-term potentiation occurs during learning. A new direction has proved to be more successful. Investigation of changes in the amygdala (a part of the brain associated with emotional response) after rats had been trained to fear a sound, found that postsynaptic neurons in the amygdala failed to produce any noticeable increase in electrical current, suggesting they had already been potentiated by their presynaptic partners.

Tsvetkov, E., Carlezon Jr.,W.A., Benes, F.M., Kandel, E.R. & Bolshakov, V.Y. 2002. Fear Conditioning Occludes LTP-Induced Presynaptic Enhancement of Synaptic Transmission in the Cortical Pathway to the Lateral Amygdala. Neuron, 34, 289-300.

Fruit flies might help us discover how the brain knows which brain connections to strengthen

Memory in fruit flies can be improved by boosting the level of a protein called PKM. The research may provide some answers to the burning question of how particular synapses are chosen. While it is generally agreed that memories are stored as changes in the number and strength of the connections between brain neurons (synapses), it has not been known how the particular synapses involved in a memory or learned skill are selected. It is thought that PKM may be involved in a process that 'tags' synapses during memory formation.

Drier, E.A., Tello. M.K., Cowan, M., Wu, P., Blace, N., Sacktor, T.C. & Yin, J.C.P. 2002.Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster. Nature Neuroscience, 5 (4),316–324.

The clearing away of excess glutamate may be important for long-term memory

Experiments with rats have demonstrated that levels of transport molecules for glutamate – chemicals that latch on to and “sweep away” glutamate – increase significantly in the period after the onset of long-term potentiation – the process believed to underlie long-term learning. This suggests that the regulation of glutamate uptake by the transport molecules may be important for maintaining the strength of connections among the neurons. Deficiencies in glutamate transporters have been implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis, or Lou Gherig’s disease.

Levenson, J., Weeber, E., Selcher, J.C., Kategaya, L.S., Sweatt, J.D. & Eskin, A. 2002. Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake. Nature Neuroscience, 5,155–161.

Identification of key brain protein for long-term memory

Using mice, scientists have identified a key brain protein involved in retaining memories, which could help explain why some things are remembered and some are not. The protein CREB (cAMP response element binding protein) apparently primes brain cells to retain long-term memories. Neurons in mice engineered to express a chimeric CREB protein were found to need a smaller first stimulus to generate a lasting increase in synaptic strength (long-term potentiation).

Barco, A., Alarcon, J.M. & Kandel, E.R. 2002. Expression of Constitutively Active CREB Protein Facilitates the Late Phase of Long-Term Potentiation by Enhancing Synaptic Capture. Cell, 108 (5), 689-703.

The neural basis for motor learning

Learning happens when a brain cell gets stimulated in a way that reduces its ability to respond to a particular brain messenger called glutamate. In the cerebellum there are very large, strangely shaped brain cells called Purkinje cells that receive more connections than other types of neurons and fire 50 times per second even when you're sleeping. These cells are involved in simple motor learning processes. A recent study provides support for an earlier study that found there are fewer receptors for glutamate on the surface of neurons during long-term synaptic depression, by demonstrating that the other three possible causes for this reduced response to glutamate do not occur.

Linden, D.J. 2001.The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance. Proc. Natl. Acad. Sci. USA, 98 (24), 14066-14071.