When I was young, I used to ask my mum what it was like when she was a child. Her response of ‘I don’t remember it was so long ago’ always astounded me. I was convinced that I would remember everything! Flash forward, and while I have some strong, distinct memories from my childhood, much of it is gone, just like my mum’s. So what are memories? How are they formed and stored and, how do we lose them?
Memory is the retention of knowledge. Both neuroscientists and physiologists agree that this is a broad term covering different aspects of knowledge accumulation. In a general sense, this covers whether the knowledge is purely emotional, linked to a time and place, or if it is related to environmental stimuli.
Much of what has been gleaned about memory comes from medical conditions in which people cannot retain memory or demonstrate memory loss. For example, in individuals with Alzheimer’s, it has been demonstrated that the hippocampus region of the brain is necessary to memory formation. It has been found that there are certain proteins in the hippocampus that are targeted by beta-amyloid peptides (small proteins that are found in the brain tissue of individuals with Alzheimer’s) that result in memory loss. Restoring the levels of these proteins in mouse models of Alzheimer’s restores the ability to learn and remember.
The hippocampus has been shown to be integral in the formation of episodic memories. An episodic memory is one which recall is via the stimuli of a place and/or time. New episodic memories can use the ‘parameters’ of a previous episodic memory and retrieval can involve thoughts and emotions of other memories. This can be why one place or emotion can trigger a multitude of memories! This has been shown experimentally from imaging of the brain. The area of the brain involved in performing an activity associated with a particular place was the same area used to conduct recall of an episodic memory associated with the same location. It has also been demonstrated that stimulation of the hippocampus produces a similar neural response to novel stimuli.
I will remember for ever and ever
So how is it that we fail to remember a conversation we had yesterday but can recall the phone number of the first house we ever lived in?
This comes down to short-term memory versus long-term memory.
Short-term memory is often also referred to as working memory (WM), and is retained for approximately 15-30 seconds. These memories are in a readily available state and usually apply to a task being performed. Repetition of the task or repeated exposure to the stimuli shunts the memory to long-term recall.
A process termed long term potentiation (LTP), is the persistent strengthening of neural cell structures called synapses in response to recent repeated activity. These synapses also exhibit plasticity, a term for the ability of synapses to weaken or strengthen in response to increases or decreases in activity. Memories that ‘fade’ are a phenomenon that neuroscientists call memory extinction, where a conditioned response is forgotten as older memories are replaced with new experiences.
Physiologists have demonstrated that dopamine plays a role in memory formation, in particular short-term memory. Neurons in the hippocampus that are receptive to dopamine will respond rapidly to novel stimuli, but as the stimuli become more familiar, the cells no longer respond. And, interfering with dopamine can block LTP, while making cells more receptive to dopamine enhances LTP.
As it is known that there are also learned responses based on both reward and behaviour, how are memory systems (i.e. WM vs LTP vs reward-based memory formation) recruited?
It is the general consensus that in the case of dopamine and LTP, it is only for stimuli that will be behaviourally advantageous. For other memory systems, recruitment of a system is based on the anticipated demands of a memory and can involve a feedback mechanism that predicts the outcome from interaction with stimuli.
This is where it can become a little confusing! The different parts of the brain control different memory systems. As discussed, the hippocampus is involved in LTP while the prefrontal cortex, for example, is involved in the maintenance and manipulation of WM.
One study demonstrated that if an individual was distracted or had increased delay between memory recall during a task that required WM, LTP increased with a decline in WM accuracy. The authors concluded that the anticipation of increased difficulty in completing or performing WM tasks led to a shift away from WM in order to preserve high-level performance.
It’s in the genes?
Very little is known about the biology of memory. Studies into Alzheimer’s have yielded much of the information about proteins that are crucial to retaining memories.
Neuroscientists combine the memory tests with investigating what is going on at the genomic level, and have found that different genes are activated along with differences in protein production. This can depend on the memory system. However, it is increasingly obvious that epigenetics plays a very important role. Modifications to DNA and proteins that change their activity without changing the genetic or protein code are rapid and occur in response to environmental stimuli. Furthermore, these changes are plastic, which as discussed, is important to memory formation and retention. This is an exciting area of research, with much more to come!
It has been demonstrated that diet can affect memory. In particular, a high fat diet (HFD) can result in poor memory retention, and in animal studies, disrupts learning and performance. It is known that a HFD results in insulin resistance of cells in the hippocampus that impairs insulin signalling.
One study observed that mice on a HFD exhibited reduced exploration time of a novel object, and when re-introduced to the object, spent more time investigating the new object compared to control diet mice. These results indicated that both WM and LTP were affected by the HFD. When the diets were changed, the effects on memory were reversed. Food for thought?!
Liar, liar pants on fire!
The demonstrated plasticity of memory formation and recall can also result in false memories. A false memory is the recall of experiencing something that wasn’t actually experienced.
There are two types of false memories, misinformation-formed and spontaneous false memory formation.
Studies have demonstrated that children seem particularly susceptible to spontaneous false memory formation, while in adults sleep deprivation can be a cause. If a person is sleep-deprived at the time of being presented with the stimuli and later provided with misinformation, their recall of the events can be different to what occurred.
This has also been demonstrated in individuals who exhibit ‘total recall’. These people have an ability to recall memories in rich detail unaided by mnemonics or memory aids. Memory recall from these individuals can also be corrupted by misinformation or misleading suggestions.
With all that we have learned about memory formation and retention, what about age-related memory loss?
Age-related memory loss is associated with a reduction in the activity of genes involved in plasticity, degradation or loss of neurons, and decreased plasticity. The hippocampus in particular appears to exhibit age-related decay that can lead to a loss of autobiographical recall.
However, not all memory systems are affected by age. One study showed that there were not age-related differences in the ability to learn configural tasks, but that there were delayed response times i.e. older adults repeated the tasks more slowly. The older adults did show a deficit in recalling tasks associated with newly learned episodic memories, with higher false memory recall. This was further confounded if several cues could initiate the retrieval of a memory.
However, all is not lost. A recent study demonstrated that the injection of blood from young mice could counteract ageing at the molecular, structural, functional and cognitive levels in the hippocampus of aged mice!
While the authors observed these changes, they had no data to explain why and how the changes occurred. They cited that it was possibly ‘pro-youthful’ factors that promote regeneration of decaying tissue or affect the activity of ‘pro-ageing’ factors. Current literature suggests that stem cells in the young mouse blood may play a role.
Stress is also linked to poor memory retention and recall, as is a lack of sleep.
While it appears much is known about memory, it is acknowledged that there is still a long way to go to understand the brain and memories. Unfortunately, progress is generally made by understanding how something has gone wrong.