Your own name. What you were doing when you heard that President Kennedy had been shot or that we had landed on the moon. How to play the piano. The birth of your first child. Some things are indelibly imprinted in your mind. You can instantly recall every detail or carry out the action without effort. Other memories are fuzzier: What you had for dinner last Tuesday. Foreign language verbs you learned long ago. Reconstructing the steps for programming your cell phone that your son just taught you. Why do some things stick in our brains like glue, while others drift away, and yet others are lodged there partially or imperfectly?
This issue of Connections presents the first installment of a two-part series about memory. This article will examine the current understanding of memory and how the brain stores and retrieves information. Part two will look at normal age-related changes in memory and current theories about what happens to memory in neurodegenerative diseases such as Alzheimer’s disease.
Of all human capacities, few spark our interest and inspire speculation more than memory. This ability to acquire, store, and use myriad types of information in countless ways is basic to our identity and allows us to function meaningfully in the world. More than just a stagnant repository of facts and miscellaneous knowledge, memory is a highly interactive and dynamic collection of processes that reflect and inform who we are as unique individuals.
The importance of memory becomes clearest when it is gone. The capacity to learn and remember—among the many characteristics that make us human—is eroded and ultimately destroyed when memory-robbing diseases such as Alzheimer’s disease and other dementias strike.
How does the brain learn and transform experiences and sensory input into memories? Are there different types of memory? How do injury and disease impair memory? Since the beginnings of modern neuroscience in the 19th century, scientists in disciplines ranging from molecular biology to psychology have explored these questions, and the advent of new technologies has enhanced their ability to piece together the cellular, molecular, and behavioral components of this remarkable ability.
Most experts agree that at least several distinct memory systems exist—sensory, short-term, working, and long-term—and that these systems interact continuously to give rise to the phenomenon of memory as we experience it in our everyday lives.
As we move through the world, we encounter hundreds and thousands of sensations. These are perceived through sight, sound, smell, taste, and touch. Each of these senses is associated with a type of memory that allows us briefly to retain impressions of specific experiences after the specific sensory stimuli have ceased. Although these perceptions flow into our sensory memory automatically, they decay within seconds if we do not consciously attend to them. Sensory memory, then, acts like a buffer that temporarily stores our sensory experiences and rapidly jettisons all but those to which we specifically direct our attention.
Experts believe that the stimuli that receive sufficient conscious attention pass selectively into short-term memory, a temporary holding tank for information. As anyone who has tried to remember a new phone number long enough to dial it knows, the storage capacity of this system is very limited, and the retention of information in short-term memory is easily disrupted by interference.
Another distinct way in which the brain temporarily holds information is through working memory. This type of memory is used to hold information for a short time while the brain manipulates and processes it. For example, working memory is used in processes that require reasoning, such as retaining the meaning of several sentences to understand an entire paragraph, or performing and retaining all of the steps of a mental calculation to arrive at a final answer.
Long-term memories, which experts say are those that endure for more than 30 seconds, are classified as either declarative or procedural, according to the type of information and learning processes involved.
Declarative memory involves facts and events learned through conscious recall. Declarative memory is further subdivided into semantic and episodic memory, once again according to the type of information involved. Semantic memories are independent of context, such as time, place, or circumstances. They consist of our abstract knowledge of the world, such as the meanings of words; the size, shape, and color of objects; our implicit understanding of social customs; or our knowledge of our own time and place. Because we are repeatedly exposed to such information throughout our lives, semantic memories are rapidly and effortlessly recalled. Episodic memories, in contrast, are highly contextual memories of the events that have occurred in our own lives and include the time and place of these events as well as their sensory and emotional associations.
Procedural memory involves “how to” knowledge, such as the specific patterns of hand and finger movements required to play the piano or the muscle actions necessary to ride a bicycle. Procedural memories are acquired through repetition rather than active recall and can be used without conscious effort.
Types of memory also can be distinguished according to their temporal direction, that is, whether they are recollections of past learning or events (retrospective memory) or involve content to be remembered for the future (prospective memory), such as remembering your dentist appointment next Thursday morning. Retrospective memory includes both episodic and semantic memory.
Scientists believe that no one area of the brain is solely responsible for forming and storing memories. A number of areas are involved, each with varied responsibilities for perceiving, processing, and analyzing information as well as for storing it as different types of memory.
The hippocampus and associated medial temporal lobe structures are involved in the formation of memories. These regions are connected to the cerebral cortex, the extensive layers of neurons and supporting brain cells that form the outermost part of the brain. The cortex is involved in the regulation of many functions, including those involved in memory, attention, planning, and decision making. Declarative memories formed when a person is awake are initially stored in the hippocampus. These memories, which are somewhat fragile and vulnerable to disruption, are eventually stored as durable long-term memories throughout the cortex in a process called consolidation. If sleep is disrupted during this consolidation process, memory storage may be impaired.
The cerebellum—the region of the brain that regulates balance and coordination—also is in charge of forming and storing procedural memories involving motor activities, such as how to swim or tap dance. The amygdala, an almond-shaped structure next to the hippocampus, is involved in the emotional aspects of memory formation and storage. Was an event associated with pleasure, pain, or fear? The strength of these emotional associations helps determine whether and how strongly an event is retained in memory.
For a long time, most neuroscientists thought that the adult brain could not generate new neurons. It was thought that memories were created and stored through modifications to existing brain structures rather than through the addition of new cells. Researchers could only speculate what these modifications might be, where exactly in the brain they might occur, or how they might come about.
The explosion of new tools and techniques in the mid-1900s revolutionized understanding of the anatomy and physiology of the brain and the ways that neurons communicate with each other. These findings have allowed scientists to gain an increasingly sophisticated understanding of how memories are formed and stored.
Neurons communicate with each other by means of slender extensions called dendrites and axons that project from the body of the cell. Incoming signals received by the dendrites are conveyed to the cell body and are sent along the axon to the dendrites of other neurons. The axon of one neuron does not actually contact the dendrites of the next cell in the network. Instead, these structures are separated by a microscopic gap called a synapse. Signals move across this gap by chemical messengers called neurotransmitters. Neurotransmitter molecules move across the synaptic space and bind with specialized receptors clustered at sites along the receiving end of dendrites.
When neurotransmitters activate a dendrite’s receptors, they open channels through the cell membrane into the receiving neuron’s interior. These channels allow electrically charged particles called ions to flow into or out of the cell. This flow of ions changes the balance of electrical charges inside and outside the cell and determines what the receiving nerve cell will do. The change in electrical charge may cause the nerve cell to “fire,” sending an electrical signal down the axon that releases neurotransmitters into the synapse, or may cause it to become less active. Sometimes, the neurotransmitter released at the synapse is “inhibitory,” making it less likely that the receiving neuron will fire and send a signal down its axon and on to other neurons. At other times, the released neurotransmitter is “excitatory,” making it more likely that a signal will be sent down the axon of the receiving neuron to other neurons in the network. Any one synaptic firing isn’t sufficient to cause a neuron to send an electrical or chemical signal to the next neuron, however. Neurons continuously receive a combination of excitatory and inhibitory signals from perhaps thousands of synaptic connections, and the sum of all these inputs causes the cell to send or not send a signal to the next neuron.
In 1949, Donald Hebb, a Canadian psychologist, using previous work from a Spanish neuroscientist named Ramón y Cajal, suggested, for the very first time, a cellular mechanism for the formation of memories. Cajal had hypothesized that learning and memory rely on the strengthening of communications between neurons, and Hebb proposed that simultaneous activity among neurons that are connected in a network would selectively strengthen their synaptic connections. Connections between neurons that were not active at the same time would be weakened or left unchanged.
In 1973, neuroscientists Terje Lomo and Timothy Bliss reported a discovery of precisely the type of increase in synaptic strength proposed by Hebb nearly 25 years earlier. They found that administering a brief, high-frequency electrical stimulus to excitatory nerve pathways in the hippocampus of rabbits produced a long-lasting enhancement in the response of the receiving neuron to subsequent stimuli. As news of the discovery of this effect, dubbed long-term potentiation (LTP), spread through the neuroscience community, its implications were immediately apparent: This might be the cellular mechanism suggested by Hebb by which information is represented and stored in the brain.
Over the past 30 years, LTP has been the focus of intense research and is now the best-studied and best-known form of “synaptic plasticity,” the term neuroscientists use to refer to the inherent capacity of the synapse to alter its behavior in response to neural activity. LTP has been found in several regions of the brain outside the hippocampus and is widely assumed to be the physiological basis of at least some forms of learning and memory.
Another important contribution of this work is that scientists have been able to decipher how short- and long-term memories are formed. Short-term memory involves a temporary strengthening of connections between existing synapses, allowing the synapse to be sensitized to later signals. However, when an event is significant enough (such as the birth of a child) or repeated enough times (such as learning how to type or memorizing your spouse’s work telephone number), something else happens to transform the short-term memory into a long-term memory. Synapses in the brain fire sufficiently to send an especially loud and clear message to neurons that the event must be recorded. This message sets off a biochemical process within the cells that causes specific genes to initiate the production of synapse-strengthening proteins. These proteins find the synapses that are holding that event as a short-term memory and permanently strengthen their connections. From then on, it doesn’t take much brain power to recall the event.
All of us have experienced lapses of memory when we couldn’t remember where we left the car or drew a blank when trying to put a name to a face. Sometimes, though, those temporary memory lapses become permanent memory losses. What happens in the brain to cause permanent changes to memory? How do neurodegenerative diseases like AD or frontotemporal dementia affect the brain in such a way as to destroy memory? The next article in this series will examine these questions and report on new research that is pushing the boundaries of knowledge about this most fascinating of human characteristics.