Part I: Reconstructing Memory
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Dr. André Fenton explains the neurobiological factors that maintain memory in our brains. As he describes, memory is a reconstructive process, whereby recollection of a particular experience involves the brain’s active rebuilding of the memory. In his first lecture, Fenton outlines how scientists have been able to associate the electrical (action potential) discharge of specific neurons with particular experiences and memories. Studying the rat hippocampus, scientists can decode information like where the rat thinks it is from the pattern of action potentials of the population of neurons. These studies reveal that the pattern of action potentials in a network of neurons encodes aspects of the external world which define experiences, thoughts and memories.
In his second lecture, Fenton provides a framework to understand the molecular mechanisms that affect acquiring and persistently storing memory. As he explains, synapses regulate the flow of information between neurons. The process of learning (memory acquisition) requires electrochemical communication between neurons across their synapses and this communication itself can change the synapses to subsequently make the communication easier and harder. One of these changes, called long-term potentiation (LTP) of synaptic transmission, strengthens the communication. An active place avoidance memory test for rodents, requires the animal to avoid uncomfortable situations (e.g. electrical shock) by learning and remembering where shocks were experienced. Using this memory test the Fenton lab showed that Protein Kinase M zeta is essential for the persistence of LTP and memory across days.
To make adaptive decisions, animals need to evaluate information from the environment by coordinating information from multiple sources, a process known as cognitive control. Cognitive control is impaired in diverse forms of mental illness, including schizophrenia. Fenton’s lab used a rat model of the neurodevelopmental origins of schizophrenia to study cognitive control in these animals using variants of the active place avoidance task. They showed that adult schizophrenia-model rats were error prone when cognitive control was needed to deal with conflicting sources of information and the patterns of electrical activity in their brains were disorganized. Remarkably, adult schizophrenia-model animals that were trained to use cognitive control in adolescence had neither the disorganized patterns of brain electrical activity nor the cognitive control deficit, even though their brains were damaged. These studies demonstrate that cognitive training to acquire and maintain memories reorganizes how the brain works, and this alone can inoculate against future mental dysfunction.
Dr. André Fenton earned his B.Sc. in Biology in 1990 from McGill University in Montreal, where he studied the neurobiology of crickets. After college, he started studying the hippocampus when he worked as a research assistant with Jan Bureš at the Institute of Physiology in Prague. In the Bureš lab, Fenton developed the rotating arena, a device used worldwide to study how rats process spatial information to form, maintain and judiciously use memories. During his Ph.D. at SUNY Downstate he studied neurons involved in navigation and spatial memory. In 2006, in collaboration with Dr. Todd Sacktor, he published a paper establishing the importance of protein kinase M zeta for maintaining memory and long-term potentiation, a crucial breakthrough in neuroscience. Fenton is a professor at NYU’s Center for Neuroscience since 2010, and his laboratory continues to study how brains store experiences as memories, and the role of protein kinase M zeta in this process.
Fenton co-founded Bio-Signal Group, a medtech company that develops and sells miniaturized electroencephalography (EEG) machines and easy-to-use electrodes to assess brain function by measuring electrical brain activity from the scalps of people. Enabling people to assess brain function anywhere and anytime helps patients and doctors optimally manage neurological emergencies.
- Karl Deisseroth Discovery Talk: Development of Optogenetics
- Mu-ming Poo iBioSeminar: Learning and Memory: From Synapse to Perception
- Karel Svoboda iBioSeminar: Optical Studies of Individual Synapses
- Torsten Wiesel Discovery Talk: Exploring the Visual Brain
Fenton, A. A. (2015) Coordinating with the "Inner GPS". Hippocampus 25: 763-769
Fenton, A. A. (2015) Excitation-inhibition discoordination in rodent models of mental disorders. Biol Psychiatry 77: 1079-1088
Kelemen, E. & A. A. Fenton (2016) Coordinating different representations in the hippocampus. Neurobiol Learn Mem 129: 50-59
Mitchell, K. J., et al. (2013) A Framework for the Use of Models in Schizophrenia. Schizophrenia: Evolution and Synthesis. S. M. Silverstein, B. Moghaddam and T. Wykes. Cambridge, MA, MIT Press: 212-226
Sacktor TC (2011) How does PKMzeta maintain long-term memory? Nat Rev Neurosci 12:9-15
Fenton, A. A., et al. (2008) Unmasking the CA1 ensemble place code by exposures to small and large environments: more place cells and multiple, irregularly-arranged, and expanded place fields in the larger space. J Neurosci 28: 11250-11262
Kelemen, E. & A. A. Fenton (2013) Key features of human episodic recollection in the cross-episode retrieval of rat hippocampus representations of space. PLoS Biol 11(7): e1001607
Lee, H., et al. (2012) Early cognitive experience prevents adult deficits in a neurodevelopmental schizophrenia model. Neuron 75: 714-724
Pastalkova, E., et al. (2006) Storage of spatial information by the maintenance mechanism of LTP. Science 313: 1141-1144
Serrano, P., et al. (2008) PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol 6(12): 2698-2706
Tsokas, P., et al. (2016) Compensation for PKMzeta in long-term potentiation and spatial long-term memory in mutant mice. Elife 5