The ability to learn associations between events is critical for survival, but it has not been clear how different pieces of information stored in memory may be linked together by populations of neurons. In a study published April 2nd in Cell Reports, synchronous activation of distinct neuronal ensembles caused mice to artificially associate the memory of a foot shock with the unrelated memory of exploring a safe environment, triggering an increase in fear-related behavior when the mice were re-exposed to the non-threatening environment. The findings suggest that co-activated cell ensembles become wired together to link two distinct memories that were previously stored independently in the brain.
“Memory is the basis of all higher brain functions, including consciousness, and it also plays an important role in psychiatric diseases such as post-traumatic stress disorder,” says senior study author Kaoru Inokuchi of the University of Toyama. “By showing how the brain associates different types of information to generate a qualitatively new memory that leads to enduring changes in behavior, our findings could have important implications for the treatment of these debilitating conditions.”
Recent studies have shown that subpopulations of neurons activated during learning are reactivated during subsequent memory retrieval, and reactivation of a cell ensemble triggers the retrieval of the corresponding memory. Moreover, artificial reactivation of a specific neuronal ensemble corresponding to a pre-stored memory can modify the acquisition of a new memory, thereby generating false or synthetic memories. However, these studies employed a combination of sensory input and artificial stimulation of cell ensembles. Until now, researchers had not linked two distinct memories using completely artificial means.
With that goal in mind, Inokuchi and Noriaki Ohkawa of the University of Toyama used a fear-learning paradigm in mice followed by a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neuronal excitability, and then delivering blue light through an optic fiber to activate those cells. In the behavioral paradigm, one group of mice spent six minutes in a cylindrical enclosure while another group explored a cube-shaped enclosure, and 30 minutes later, both groups of mice were placed in the cube-shaped enclosure, where a foot shock was immediately delivered. Two days later, mice that were re-exposed to the cube-shaped enclosure spent more time frozen in fear than mice that were placed back in the cylindrical enclosure.
The researchers then used optogenetics to reactivate the unrelated memories of the safe cylinder-shaped environment and the foot shock. Stimulation of neuronal populations in memory-related brain regions called the hippocampus and amygdala, which were activated during the learning phase, caused mice to spend more time frozen in fear when they were later placed back in the cylindrical enclosure, as compared with stimulation of neurons in either the hippocampus or amygdala, or no stimulation at all.
The findings show that synchronous activation of distinct cell ensembles can generate artificial links between unrelated pieces of information stored in memory, resulting in long-lasting changes in behavior. “By modifying this technique, we will next attempt to artificially dissociate memories that are physiologically connected,” Inokuchi says. “This may contribute to the development of new treatments for psychiatric disorders such as post-traumatic stress disorder, whose main symptoms arise from unnecessary associations between unrelated memories.”
More information: Cell Reports, Ohkawa et al.: “Artificial Association of Pre-Stored Information to Generate a Qualitatively New Memory” www.cell.com/cell-reports/abst… 2211-1247(15)00270-3
Of the mice that received the treatment, 75 percent got their memory functions back.
Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques – structures that are responsible for memory loss and a decline in cognitive function in Alzheimer’s patients.
If a person has Alzheimer’s disease, it’s usually the result of a build-up of two types of lesions – amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.
Neurofibrillary tangles are found inside the neurons of the brain, and they’re caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.
As we don’t have any kind of vaccine or preventative measure for Alzheimer’s – a disease that affects 343,000 people in Australia, and 50 million worldwide – it’s been a race to figure out how best to treat it, starting with how to clear the build-up of defective beta-amyloid and tau proteins from a patient’s brain. Now a team from the Queensland Brain Institute (QBI) at the University of Queensland have come up with a pretty promising solution for removing the former.
Publishing in Science Translational Medicine, the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain’s microglial cells to activate. Microglila cells are basically waste-removal cells, so they’re able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer’s.
The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks – a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.
“We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics,” one of the team, Jürgen Götz, said in a press release. “The word ‘breakthrough’ is often misused, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach.”
The team says they’re planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017.
You can hear an ABC radio interview with the team here.
It might seem like science fiction but a new implant which attaches directly to the spine could help paralysed people walk again
Paralysed patients have been given new hope of recovery after rats with severe spinal injuries walked again through a ‘groundbreaking’ new cyborg-style implant.
In technology which could have come straight out of a science fiction novel or Hollywood movie, French scientists have created a thin prosthetic ribbon, embedded with electrodes, which lies along the spinal cord and delivers electrical impulses and drugs.
The prosthetic, described by British experts as ‘quite remarkable’, is soft enough to bend with tissue surrounding the backbone to avoid discomfort.
Paralysed rats who were fitted with the implant were able to walk on their own again after just a few weeks of training.
Researchers at the Ecole Polytechnique Fédérale de Lausanne are hoping to move to clinical trials in humans soon. They believe that a device could last 10 years in humans before needing to be replaced.
The implant, called ‘e-Dura’, is so effective because it mimics the soft tissue around the spine – known as the dura mater – so that the body does not reject its presence.
“Our e-Dura implant can remain for a long period of time on the spinal cord or cortex,” said Professor Stéphanie Lacour.
“This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury.”
Previous experiments had shown that chemicals and electrodes implanted in the spine could take on the role of the brain and stimulate nerves, causing the rats’ legs to move involuntarily when they were placed on a treadmill.
But this is the first study to show a simple gadget can help rats walk again and be tolerated by the body.
Scientists have struggled to find a device which will sit next to the spine or brain because both are surrounded by a protective envelope of tissue which the hard surface of implants can rub against, causing inflammation and scar tissue
However the new gadget is flexible and stretchy enough that it can be placed directly onto the spinal cord. It closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and drugs which activate cells.
The implant is made of silicon and covered with gold electric conducting tracks that can be pulled and stretched. The electrodes are made of silicon and platinum microbeads which can also bend in any direction without breaking.
Writing in the journal Science, where the results were published, science writer Robert Service said: “Soft flexible nerves connected to unyielding silicon and metal – the combination has spawned many a Hollywood cyborg.
“The implants Lacour’s team created still have to be wired to the outside world to operate, but she and her colleagues are designing wireless versions of the technology. Watch out, Hollywood, reality is catching up.”
The research was praised by British scientists.
“The work described here is a groundbreaking achievement of technology, which could open a door to a new era in treatment of neuronal damage,” said Dr Duško Ilić, Reader in Stem Cell Science at King’s College London.
“Until now, the most advanced prostheses in intimate contact with the spinal cord caused quite substantial damage to tissue in just one week due to their stiffness.
“There is still a long way to go before we may see any practical use of such neuroprostheses in humans. But it may be that it is something that could potentially be developed for use in humans in the foreseeable future.”
Prof John Hunt, Head of Unit of Clinical Engineering, University of Liverpool, added: “This study in rats is an interesting one and it could have the potential to be quite promising in terms of being applicable to people with spinal injuries.”
The implant has been primarily tested in cases of spinal cord injury in paralyzed rats but researchers believe it could eventually be used in epilepsy, Parkinson’s disease and pain management.
The scientists are planning to move towards clinical trials in humans within the next few years.
The research was published in the journal Science.
Sleep is a critical period for memory consolidation, and most people don’t get enough. Research has shown that even brief periods of sleep deprivation can lead to deficits in memory formation.
In a new study, published in the Journal of Neuroscience, a team led by scientists from the University of Pennsylvania found that a particular set of cells in a small region of the brain are responsible for memory problems after sleep loss. By selectively increasing levels of a signaling molecule in these cells, the researchers prevented mice from having memory deficits.
Robbert Havekes was the lead author on the study. He is a research associate in the lab of Ted Abel, the study’s senior author and Brush Family Professor of Biology in Penn’s School of Arts & Sciences. Coauthors from the Abel lab included Jennifer C. Tudor and Sarah L. Ferri. They collaborated with Arnd Baumann of Forschungszentrum Jülich, Germany, and Vibeke M. Bruinenberg and Peter Meerlo of the University of Groningen, The Netherlands.
In 2009, a group from Abel’s lab published a study in Nature that identified the cyclic AMP, or cAMP, signaling pathway as playing a role in sleep-loss-associated memory problems. Whereas depriving mice of sleep impaired their spatial memory, restoring levels of cAMP in their brain prevented this effect.
“The challenge following this important study,” Abel said, “was to determine if the impact of sleep deprivation was mediated by particular regions of the brain and particular neural circuits. We suspected that the hippocampus, the brain region that mediates spatial navigation and contextual memory, was critical.”
In the current work, they set out to answer these questions. They targeted excitatory neurons because of their importance in transmitting signals in the brain and the fact that their functioning relies on cAMP signaling. The limitation of previous studies was that they lacked a way to increase cAMP in just one area of the brain in a cell-type specific fashion. Havekes, Abel and colleagues devised a way of doing this that they term a “pharmacogenetic” approach, blending genetic modification and drug administration.
They engineered a non-pathogenic virus to harbor the gene encoding the receptor for the protein octopamine, which triggers cAMP pathway activation in fruit flies but is not naturally found in the brains of mice. The researchers injected this virus into the hippocampus of mice so that the excitatory neurons in that region alone would express the octopamine receptor.
“It sounds weird. Why would you put a receptor there that is never going to be activated?” Havekes said. “The trick is, you follow that up by giving mice the ligand of the receptor, which is octopamine, and that will activate the receptors only where they are present.”
The team confirmed that only the excitatory hippocampal neurons expressed the receptor and that they could selectively increase cAMP levels in only these cells by giving the mice a systemic injection of octopamine.
“This way, we could manipulate the cAMP pathways that we previously saw being affected by sleep deprivation but selectively in specific neural circuits in the brain,” Havekes says.
With this pharmacogenetic tool in hand, Havekes, Abel and colleagues began the sleep deprivation tests with the mice expressing the octopamine receptor in their hippocampus. First the researchers trained mice in a spatial memory task. They put them in a box that had three different objects, each in a distinct location.
Then, because previous research had shown that cAMP signaling contributes to hippocampus-dependent memory consolidation in two time windows—first directly after training and again three to four hours after training—the researchers gave mice in the experimental groups injections of octopamine in both of these windows to boost cAMP levels.
Mice receiving the cAMP boost were divided into two groups: One was left to sleep undisturbed, while the other was sleep-deprived for five hours by gently tapping their cage or rearranging their bedding.
One full day after the initial training, all of the mice were tested again. This time, there was a twist: one of the objects originally in the box had been moved to a new location.
“If the mice had learned and remembered the location of the objects during their training, then they would realize, okay, this is the object that has moved, and they’ll spend more time exploring that particular object,” Havekes explained. “If they didn’t remember well, they would explore all the objects in a random fashion.”
The researchers found that the sleep-deprived mice that received the octopamine injections spent more time exploring the object that had moved, just as mice that had not been sleep deprived did. On the other hand, sleep-deprived mice that didn’t express the receptor explored all the objects at random, a sign that they had failed to remember the locations of the objects from their initial training as a result of the brief period of sleep deprivation.
“What we’ve shown is this memory loss due to sleep deprivation is really dependent on misregulation of cAMP signaling in the excitatory neurons of the hippocampus,” Havekes said.
As a next step, the group would like to explore what cAMP is doing to help consolidate memory. They would also like to investigate how other cell types in the brain, such as astrocytes, might be affected. And finally, while this study focused on the impact of a brief period of sleep deprivation, Havekes is curious to know how not getting enough sleep on a daily basis, as is more similar to human experiences, might be affecting memory.
“Thinking about people who do shift work or doctors who work long hours, if we can tackle the cognitive problems that result from sleep loss, that would be a great thing,” Havekes said.
“At least in the mouse using these sophisticated tools, we’re able to reverse the negative impact of sleep deprivation on cognition,” Abel said.
I figured it is about time to write something about the blog’s title, bell’s palsy, since I’ve seen there are a lot of people searching for this topic about facial paralysis.
Bell’s palsy is a common condition that presents with an acute onset of lower motor neuron (LMN – could say like peripheral nerves) facial weakness affecting the muscles on one side of the face.
People of all ages may be affected, including children, although it is most common in patients aged 30-50 years. The exact cause in not known, but there are certain conditions known to be responsible.
If we take a look in pathogenesis, how the condition evolves, we see that there is segmental demyelination in a local conduction block proximally. And what this actually means? Every nerve has its sheath around that is made of substance called myelin. This myelin sheath does not cover the whole nerve, but in segments, leaving tiny gaps, called Nodes of Ranvier (take a look at the picture below). And these gaps are like capacitors that stores electrical charge and allows bursts of electric impulses (know as action potentials) to move along the neuron in a saltatory fashion. Think of it as the action potential would jump from one of these gaps to the next one. This actually prevents loosing the charge. Now imagine that you widen this gap. This slows the nerve conduction, spread it even more and you get a block, conduction block. Now you cannot get the full use of that nerve leaving you weakness.
Since this conduction block happens proximally (closer to its origin), it allows a relatively rapid and complete recovery in about 85% of cases. This is because myelin rapidly regenerates. In others, axonal degeneration occurs, which will produce a severe paralysis. Again, think of it as the whole neuron is cut, and that is why it is so severe. Often this is then followed by incomplete recovery associated with aberrant re-innervation, that is, fibers from the periocular muscles my regenerate and supply the mouth, and vice versa. Such faulty re-innervation may lead to “jaw-winking”, and even hemifacial spasm. Where axonal degeneration has occurred, electromyography of the facial muscles will show fibrillation and features of denervation, although these changes may not appear until some 10 days after the onset. In some instances the pathogenesis is a mixture of axonal degeneration and demyelination.
Ok, let’s leave this aside and let’s carry on and look how this condition actually presents clinically. Normally patients may present with pain in or behind the ear preceding or appearing with the development of facial weakness. There is inability to close the eye or move the lower face and mouth on one side of the face.
The lack of blinking leads to tears spilling out of the eye, which waters to cause complaints of blurred vision. The cheek is flaccid and saliva and fluids may escape from the corner of the mouth. The weakness commonly progresses over 24-72 hours to reach a maximum. In many patients there are complaints of numbness in the affected side of the face, although trigeminal sensation is spared and there should be no weakness of jaw movement, since it is supplied by the motor root of the trigeminal nerve. Trigeminal sensation is sensation on the skin of the face, because sensory innervation of it comes from fifth cranial nerve – trigeminal nerve. Hence the name.
About 40-50% of patients are aware of disturbed taste on the ipsilateral anterior part of the tongue (ipsilateral means it is on the same side as the lesion). This points to a lesion in the distal part of the facial nerve below the geniculate ganglion, but above the origin of the chorda tympani (branch of facial nerve that is responsible for taste). Many patients also notice hyperacusis (over-sensitivity to certain frequency ranges of sound and difficulty tolerating everyday sounds, some of which may seem unpleasantly loud) because the stapedius muscle (very small muscle that moves the smallest bone in the human body and makes us hear) is supplied by a branch of the facial nerve, which leaves the nerve in the facial canal proximal to the chorda tympani.
If a zoster infection is responsible, there will be herpetic vesicles on the pinna (the visible part of the ear that resides outside of the head, also called auricle or auricula) or in the external auditory canal on the affected side. Ramsay Hunt described a herpetic infection of the geniculate ganglion with the development of an acute facial palsy – Hunt’s syndrome. In some of these patients the 8th cranial nerve (auditory nerve, responsible for hearing) may also be infected, producing acute vertigo, deafness and tinnitus (ringing of the ears). A few patients may show a bilateral (on both sides) facial palsy of lower motor neuron (LMN) pattern; this may appear as part of a Guillain-Barre syndrome, from Lyme disease, from sarcoidosis or even carcinomatous meningitis.
About 85% of patients show signs of improvement within some 3 weeks of the onset. About 70% of patients recover normal function in the face but some 16% are left with asymmetry, signs of aberrant re-innervation and some weakness. An incomplete palsy at the onset or signs of recovery starting within 3-4 weeks usually are good prognostic features for recovery. This is mirrored in the electrophysiological findings. In the more severely affected, where axonal degeneration has taken place, recovery is slower and often incomplete. Recurrent facial palsies require more intensive investigation to exclude any compressive lesion on the middle ear or skull base, and to look for any systemic upset such as sarcoidosis, hypertension, diabetes.
Normally when there is suspicion of Bell’s palsy several investigations are made. Such as blood tests. Full blood count, erythrocyte sedimentation rate (ESR), fasting glucose levels, tests for Borrelia. Of course there is imaging; in selected patients MRI and/or CT scanning, chest X-ray. Electromyography (EMG) studies as these may assess the severity of damage and help in prognosis; they may also indicate a more widespread neuropathy. ENT examination…
Once all the tests are conclusive and the Bell’s palsy diagnosis is made, patients can undergo treatment. There appears to be little difference in outcome between patients treated with steroids and those who are not. Many doctors believe that a short intensive course of steroids given within 5-7 days of the onset of palsy may reduce the swelling of the facial nerve and so prevent axonal degeneration. Prednisolon 40 mg daily for 5 days and then tapered off over the next week is a typical regimen. It has been suggested that such a course should be given to all patients seen acutely with a complete palsy at the time of consultation or with impaired taste.
Because of the possible infective causation by herpes virus, acyclovir has also been used in treatment of an cute facial palsy. This certainly should be given if a zoster infection (Hunt’s syndrome) is suspected. The combination of acyclovir with steroids in those patients with complete facial palsies has also been used. Surgical decompression of the facial nerve has had its supporters over the years, although there has been no rigorous controlled trial to indicate benefit and as over 70% of patients will make a full recovery with no treatment it is hard to justify the surgical risks.
Care of the eye is always important if there is incomplete lid closure but as the cornea is not anesthetic, the patient will be aware of any intruding foreign body. Occasionally it may be necessary to suture the lids partially together, a tarsorrhaphy, to protect the eye.
In those patients left with marked residual weakness or asymmetry, a number of surgical measures may be used to try to improve their appearance. These include plastic surgery with implants of soft tissues to restore the contours. Such measures will improve the symmetry of the face at rest but are by no means a ‘cure’.
Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons – providing much-needed clues into the brain’s ability to form long-lasting memories.
These findings, reported in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.
Led by Gladstone senior investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories.
However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.
Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called “homeostatic scaling.” Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they’ve made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.
“Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day,” said Finkbeiner, who is also a professor of neurology and physiology at UC San Francisco, with which Gladstone is affiliated. “Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc’s presence at these synapses was driving the formation of long-lasting memories.”
But Finkbeiner and his team thought there was something else in play.
The Role of Arc in Homeostatic Scaling
In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc’s movements. And what they found was surprising.
“When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses – but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus,” said Erica Korb, PhD, the paper’s lead author who completed her graduate work at Gladstone and UCSF.
“A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there,” she said. “The presence of this complex and tightly regulated system is strong evidence that this process is biologically important.”
In fact, the team’s experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories. From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them – thus translating learning into long-term memories.
Implications for a Variety of Neurological Diseases
“This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself – disruptions in which have already been implicated in a whole host of neurological diseases,” said Finkbeiner. “For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain’s memory center, in Alzheimer’s disease patients. It’s possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer’s.”
Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome – a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.
“In the future,” added Dr. Korb, “we hope further research into Arc’s role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them.”
Journal reference: Abstract for “Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity” by Erica Korb, Carol L Wilkinson, Ryan N Delgado, Kathryn L Lovero and Steven Finkbeiner in Nature Neuroscience. Published online June 9 2013 doi:10.1038/nn.3429
How does short-term memory work in relation to long-term memory? Are short-term daily memories somehow transferred to long-term storage while we sleep?
Alison Preston, an assistant professor at the University of Texas at Austin’s Center for Learning and Memory, recalls and offers an answer for this question.
A short-term memory’s conversion to long-term memory requires the passage of time, which allows it to become resistant to interference from competing stimuli or disrupting factors such as injury or disease. This time-dependent process of stabilization, whereby our experiences achieve a permanent record in our memory, is referred to as “consolidation.”
Memory consolidation can occur at many organizational levels in the brain. Cellular and molecular changes typically take place within the first minutes or hours of learning and result in structural and functional changes to neurons (nerve cells) or sets of neurons. Systems-level consolidation, involving the reorganization of brain networks that handle the processing of individual memories, may then happen, but on a much slower time frame that can take several days or years.
Memory does not refer to a single aspect of our experience but rather encompasses a myriad of learned information, such as knowing the identity of the 16th president of the United States, what we had for dinner last Tuesday or how to drive a car. The processes and brain regions involved in consolidation may vary depending on the particular characteristics of the memory to be formed.
Let’s consider the consolidation process that affects the category of declarative memory—that of general facts and specific events. This type of memory relies on the function of a brain region called the hippocampus and other surrounding medial temporal lobe structures. At the cellular level, memory is expressed as changes to the structure and function of neurons. For example, new synapses—the connections between cells through which they exchange information—can form to allow for communication between new networks of cells. Alternately, existing synapses can be strengthened to allow for increased sensitivity in the communication between two neurons.
Consolidating such synaptic changes requires the synthesis of new RNA and proteins in the hippocampus, which transform temporary alterations in synaptic transmission into persistent modifications of synaptic architecture. For example, blocking protein synthesis in the brains of mice does not affect the short-term memory or recall of newly learned spatial environments in hippocampal neurons. Inhibiting protein synthesis, however, does abolish the formation of new long-term representations of space in hippocampal neurons, thus impairing the consolidation of spatial memories.
Over time, the brain systems that support individual, declarative memories also change as a result of systems-level consolidation processes. Initially, the hippocampus works in concert with sensory processing regions distributed in the neocortex (the outermost layer of the brain) to form the new memories. Within the neocortex, representations of the elements that constitute an event in our life are distributed across multiple brain regions according to their content. For example, visual information is processed by primary visual cortex in the occipital lobe at the rear of the brain, while auditory information is processed by primary auditory cortex located in the temporal lobes, which lie on the side of the brain.
When a memory is initially formed, the hippocampus rapidly associates this distributed information into a single memory, thus acting as an index to representations in the sensory processing regions. As time passes, cellular and molecular changes allow for the strengthening of direct connections between neocortical regions, enabling the memory of an event to be accessed independently of the hippocampus. Damage to the hippocampus by injury or neurodegenerative disorder (Alzheimer’s disease, for instance) produces anterograde amnesia—the inability to form new declarative memories—because the hippocampus is no longer able to connect mnemonic information distributed in the neocortex before the data has been consolidated. Interestingly, such a disruption does not impair memory for facts and events that have already been consolidated. Thus, an amnesiac with hippocampal damage would not be able to learn the names of current presidential candidates but would be able to recall the identity 16th US president (Abraham Lincoln, of course!).
The role of sleep in memory consolidation is an ancient question dating back to the Roman rhetorician Quintilian in the first century A.D. Much research in the past decade has been dedicated to better understanding the interaction between sleep and memory. Yet little is understood.
At the molecular level, gene expression responsible for protein synthesis is increased during sleep in rats exposed to enriched environments, suggesting memory consolidation processes are enhanced, or may essentially rely, on sleep. Further, patterns of activity observed in rats during spatial learning are replayed in hippocampal neurons during subsequent sleep, further suggesting that learning may continue in sleep.
In humans, recent studies have demonstrated the benefits of sleep on declarative memory performance, thus giving a neurological basis to the old adage, “sleep on it.” A night of sleep reportedly enhances memory for associations between word pairs. Similar overnight improvements on virtual navigation tasks have been observed, which correlate with hippocampal activation during sleep. Sleep deprivation, on the other hand, is known to produce deficits in hippocampal activation during declarative memory formation, resulting in poor subsequent retention. Thus, the absence of prior sleep compromises our capacity for committing new experiences to memory. These initial findings suggest an important, if not essential, role for sleep in the consolidation of newly formed memories.