RESEARCH IN THE MCNAUGHTON LAB
Dr. McNaughton’s research focuses on mechanisms of learning and memory, largely centered around hippocampus functional contributions to engram formation and alteration. This includes examination of impaired memory and memory disorders associated with aging and/or systemic damage.
Dr. McNaughton began his career as a biophysicist performing long-term synaptic potentiation and the role of this process in associative information storage. This work was highlighted by the first demonstration that “Hebbian” principles of association, which form the basis of all neural network learning algorithms, are embodied in the actual dynamics of experience dependent synaptic plasticity. In the last 15 years, Dr. McNaughton has been at the forefront of development of methods to study the large-scale interactions of neurons in the intact brain during the encoding, storage, recall and consolidation of memory. Methods developed in his laboratory now make it possible to record from several hundred cortical neurons during learning experiments in animals, providing an unprecedented window on how neurons cooperate during cognitive processing.These methods are also being directed towards the development of neuroprosthetic systems that will use direct brain recording to control muscle activity in patients with spinal injury. At the other end of the scientific spectrum, Dr. McNaughton is a key member of an interdisciplinary team involved in the development of immediate-early gene activation markers of neural activity in the brain. This method permits visualization of the recent history of activity in the brain at cellular resolution, thus allowing identification of not only which areas of the brain are activated during cognitive processing, but which specific neurons. This method will provide an important complement to non-invasive, but lower resolution, functional neuroimaging studies using magnetic resonance.
OPPORTUNITIES FOR UCI UNDERGRADUATES
Our lab has benefited greatly from the work of undergraduate researchers and we are always open to considering new opportunities for students. If you are interested, please contact McNaughton Lab Manager Geoffrey Shafer, MS to discuss your interests, background, career plans, and detailed rationale behind your desire to work in an active research environment.
My research interests are focused on understanding the ‘lifetime’ of memories in the brain, from the initial encoding, throughout the consolidation process. What mechanisms are involved in the selection of memory aspects to be remembered, what drives the dynamics of bidirectional information transfer between the hippocampus and cortex, how is the transferred information encoded and decoded, how the new memories get incorporated into the existing schema and what is the neural implementation of the extraction of semantic from episodic memories? How the spectrum of lifetime experiences affects the connectivity matrix, representational capacity and state space of neuronal networks? To this end, I use the combination of lesion techniques, environmental enrichment procedures and high density single neuron and local field potential recordings from the hippocampus and cortical structures.
Figure: LFP (top left) and single neuron (bottom left) recordings from the dorsal CA1 of the rat occurring during slow wave sleep, showing the sharp wave ripples.Top right: Averaged LFP traces filtered in ripple range, recorded from the ventral (pink) and dorsal (blue) CA1 in rat, centered at the peak of the ventral hippocampal sharp wave ripples.Bottom right: Averaged envelopes of Hilbert-transformed LFP signals (300-900 Hz) from medial prefrontal cortex (red), retrosplenial cortex (green), ventral (pink) and dorsal (blue) hippocampus, centered at the ventral hippocampal ripple peak amplitude.
My research topic focuses on hippocampal contribution to neocortical neurodynamics in the process of memory encoding and consolidation. The hippocampal formation (HF) has long been considered an essential brain structure supporting these functions. One prominent view (The Memory Index Theory) holds that the HF generates an ‘index’ for sub-attributes of ‘episodic’ memory, which is distributed among many neocortical modules. The view also suggests that during sleep the HF helps ‘consolidate’ recent episodic memories and extract general (‘semantic’) knowledge. Despite our general understanding of the theory, how exactly the HF index modulates neocortical neurodynamics needs to be experimentally confirmed. I use a combination of behavioral (e.g., environmental enrichment, spatial learning in virtual reality, classical eyeblink conditioning), optical (e.g., voltage-sensitive dye imaging, wide-field calcium imaging), and electrophysiological tools to investigate how the neocortical activity patterns differ between the brain with or without the hippocampus and how the neural patterns relate to behavior.
Since October 2014, I am a post doc fellow working under the supervision of one of the pioneers in the field of learning and memory, Prof. Bruce L. McNaughton, who provided strong evidence for the “memory trace reactivation” theory. According to this theory, the hippocampus first encodes memories for external events during wakefulness and then during subsequent periods of calmness or sleep, memory traces are “reactivated” or “replayed” in both hippocampus and cortex. These replays are considered as the underlying mechanism for memory consolidation. By using the advantages of imaging techniques, I’ll investigate the role of hippocampus in the formation of cortical replays.
I am interested in how the brain takes a large amount of complex sensory information and condenses it into a useful, interpreted summary and then stores it. At the heart of memory storage is the hippocampus, which is necessary for the encoding of new episodic memories, and processes information primarily about an animal’s physical location in an environment. We believe that location information can be used to “tag” events and provide a link that binds all the other sensory information that composes a particular memory. In my PhD work, I showed that hippocampal spiking activity in a novel environment is the same at a given location, regardless of the direction of travel through the location, but following repeated experiences along the same paths, the “tag” (neural activity pattern) for the same location can become differentiated for the two running directions, which would allow it to store two different versions of experiences in that location.
Project update coming soon!
Since the beginning of applying rigorous scientific methods to investigate psychological phenomenon, we have known that sleep is beneficial for learning and memory stabilization. Over the past century, many efforts have been made to understand this phenomenon more thoroughly. Although some illuminating insights have been made in this endeavor, the cognitive and neural mechanisms underlying this fascinating phenomenon remain outside the realm of our understanding. However, based on both theoretical evidence developed several decades ago and experimental evidence gathered more recently, it seems that a process colloquially known as “memory replay” is important for this strengthening of our memories that occurs while we sleep.
Memory replay refers to an event in the brain in which patterns of neural activity that were apparent during, and characteristic of, a particular experience are reactivated during a subsequent period of rest. If one just takes a minute to think about sleep, this concept will be almost self-evident: our dreams typically reflect what has been happening recently in our lives. Clearly, these thoughts are still present within the brain and “on our mind” during sleep! In that light, it makes intuitive sense that these patterns of neural activity that were active during learning are then reactivated during sleep. Experimental evidence also provides support for the theory that replay is important for memory. Not only have multiple experiments shown strong correlations between the neural activity occurring during learning and then during a subsequent sleep, a few studies have also demonstrated that disrupting replay leads to learning deficits in the task being performed. All of this points to memory replay as a candidate mechanism to explain the benefits effects that sleep has on learning and memory.
Figure: A rat with unilateral hippocampal lesion performing the spatial sequence task from memory. Neural activity is recorded with high density electrode arrays.
Although all this experimental evidence supports the theory that memory replay is involved in learning, the theory needs to be tested even more rigorously and the details of this phenomenon need to be discovered and explained. One prevalent idea is that a structure called the hippocampus is capable of uniquely coding our experiences which can then be indexed and the patterns of neural activity can be reactivated in other brain areas, specifically the neocortex. My interest is in understanding the dynamics of this potential indexing and hierarchical reactivation. To explore this interest experimentally, the hippocampus is lesioned unilaterally and the rat is trained on a spatial sequence memory task on a circular maze (see Figure). In this task, the animal learns that reward is given at particular locations on the maze in a particular sequence. In order to complete this task, the rat must remember where the locations are and in what order they are rewarded or what action sequence to execute. The rat then is placed in a quiet, comfortable location so it can rest quietly and sleep. Neural activity is recorded in the neocortex bilaterally throughout. Because the hippocampus has primarily ipsilateral direct connections with the neocortex, this experimental preparation allows us to investigate the effects that the hippocampus has on neocortical replay during sleep within a single animal. Our hypothesis is multifaceted: we expect to see stronger replay in the neocortex of the hemisphere with a healthy hippocampus than its contralateral counterpart. We also expect that replay of recent maze sessions (neural activity that went on during a recent behavioral session) will be stronger. A separate, but not exclusive, line of research suggests that memories are replayed in an interleaved order. If this is true, and the hippocampus is involved in the organization of this process, we might see that remote and recent memories are not interleaved or that only recent memories are replayed and remote memories cannot be properly indexed in the lesioned hemisphere.