Memory in the Mammalian Brain

The ability to remember past experiences is crucial to our survival and fundamentally defines who we are, how we think and act, and how we perceive the world around us. There are many different “types” of memories, and emerging evidence suggests that memory for different types of information relies on different brain structures. One kind of memory, and one with which we’re all familiar, is the memory for specific facts and events; this type of memory is often referred to as “episodic” or “autobiographical” memory. We now know that episodic memory is largely dependent on a brain structure called the hippocampus. The goal of our lab’s work is to better understand the biological mechanisms within the hippocampus that allow us to form lasting episodic memories.

• How does information about the world make its way into our brains? 

We receive information about the outside would through our various sensory organs (eyes, nose, skin) which are affected by energy in the environment (light, smells, touch etc.).  These organs contain specialized cells which convert energy from physical stimuli into “action potentials”, which are the electrical impulses generated by cells within our nervous system called neurons. These signals are then carried from our sensory organs to our brain, which is part of the Central Nervous System. Information for each of our senses gets sent to separate areas within our cerebral cortex that have evolved to detect one kind of sensory information. For example, visual information gets sent to visual cortex, smell information gets sent to our olfactory cortex, and touch information gets sent to our somatosensory cortex. After being processed separately by these sensory cortical areas, this information gets sent to many areas of our brain, including the hippocampus. 

• How is information represented in the central nervous system?

Our brains are composed of approximately 100 billion neurons that are interconnected to each other in complex networks at tiny gaps called synapses. When a neuron fires an action potential, it can then communicate with other nearby neurons by sending chemicals called neurotransmitters across these synapses. If the neuron is stimulated by enough of the right kind of neurotransmitter, it too will fire an action potential.  When we see a certain object, or hear a specific sound, or experience a unique episode in life, networks of interconnected neurons display a unique pattern of activation.

•  How is this information stored as a lasting memory?

We don’t really know, but we’re trying to find out. One thing we do know is that in order for us to store information about our experiences, these experiences must do more than temporarily activate networks of neurons. Rather, these experiences need to make a lasting change in the activity of these networks for that experience to form a lasting memory. It turns out that the brain does exactly that; experiences can and do change the strength of the synaptic connections between neurons that can last almost indefinitely. In other words, neurons that fire together during experience undergo lasting changes that strengthen the connections between them, which in turn makes them more likely to fire together in the future. Sometimes experience can even change the morphology of individual neurons. Changing the strength of communication between neurons and/or the morphology of neurons are two prominent forms of neuronal plasticity. It is widely believed that the permanent storage of information (i.e. “memory”) in our nervous system is critically dependent on neuronal plasticity within networks of neurons. 

• How is the hippocampus involved?

The involvement of the hippocampus in episodic memory was first discovered over 50 years ago following the report of a patient who had his hippocampus removed in order to treat severe, otherwise untreatable epilepsy. After the surgery, this patient could no longer store new episodic memories. Research since that time has revealed that the formation of episodic memories is critically dependent on neuronal plasticity within the hippocampus. Animal studies have shown that using drugs to inhibit neuronal plasticity in the hippocampus can block the formation of long-term memory. Moreover, plasticity within different parts of the hippocampus  appears to be involved in different aspects of episodic memory. For example, the dorsal (in rodents) or posterior (in humans) hippocampus is thought to be involved in the acquisition of memory for places and the sequences of events, while the ventral or anterior hippocampus is thought to be involved in the storage of the emotional significance of events.

• What happens inside hippocampal neurons when we form episodic memories?

When neurons fire rapidly, a number of things happen internally, including the activation of intracellular genes. These genes make proteins that play a crucial role in strengthening communication between these rapidly firing neurons (neuronal plasticity). One gene that appears to be very importantly involved in hippocampal synaptic plasticity is called Arc. We have shown that some types of learning that depend critically on the hippocampus also dramatically increase expression of the Arc gene and protein, and that pharmacologically blocking expression of the Arc gene within the hippocampus blocks those forms of learning while leaving other forms of memory unimpaired. We don’t know all of the steps involved – that is what we are trying to figure out – but we do have a good idea of where to look and how to do it. Our current studies examine the hippocampus on multiple levels in order to determine what each of the various “parts” (called CA1, CA2, CA3, and the dentate gyrus) of the hippocampus contribute to memory formation and how they do so. One way that we do this by examining the relationship between what rats are learning and the expression of certain genes (like Arc) in the different regions of the hippocampus. The results of one of our studies on Arc expression and learning are summarized in a presentation below. If you would like to know the details of our experiments and findings, click on the publications tab above.