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Séminaire - Sheena Josselyn & Paul Frankland"Making, breaking and linking memories" and “Hippocampal neurogenesis and forgetting”

Abstract :

Sheena Josselyn: "A fundamental goal of neuroscience is to understand how information is encoded and stored in the brain.  The physical or functional representation of a memory (the memory trace or “engram”) is thought to be sparsely encoded over a distributed memory network. However, identifying the precise neurons which make up a memory trace has challenged for scientists since Karl Lashley’s “search for the engram” in the 1950’s (Josselyn, 2015; Lashley, 1950; Josselyn, 2010; Josselyn et al., 2015).  Moreover, it was not known why one neuron (rather than its neighbour) was involved in a given memory trace. We previously showed that lateral amygdala (LA) neurons with increased levels of the transcription factor CREB (cAMP/Ca++ Responsive Element Binding protein), are preferentially activated by fear memory expression, suggesting they are selectively recruited into the memory trace (Han et al., 2007).  We, and others, went on to show that these neurons were critical components of the memory network by selectively ablating (Han et al., 2009) or inactivating them (Zhou et al., 2009).  These findings established a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace.

Furthermore, these results suggest that at least within the LA, eligible neurons compete for inclusion in a memory trace, and that the winners of this competition are determined by relative CREB function.  Although competition between neurons, axons and synapses is necessary for refining neural circuits in development, little is known about competition between neurons in the adult brain. Our recent results suggest that this neuronal competition during memory formation limits the overall size of the memory trace (number of “winning” neurons) and is a mechanism that links (or disambiguates) related memories in the LA (Rashid, et al., 2016).

                Memory impairments are a hallmark of aging, major mental illnesses (e.g., schizophrenia and depression) as well as neurological disorders (e.g., Alzheimer's and Parkinson's diseases). Therefore, understanding how the brain encodes and stores information is highly relevant to both mental health and mental illness"

“Hippocampal neurogenesis and forgetting” 

Paul Frankland :  "We are interested in how neurogenesis in the hippocampus regulates memory function. Our studies have shown that the addition of new neurons may facilitate new memory formation. Conversely, the integration of new neurons into established hippocampal circuits may erode memories already stored in those circuits. This finding changes the way we think about how hippocampal neurogenesis contributes to memory function, suggesting that it regulates a balance between encoding new memories and clearing out old memories"


Paul Frankland is a Senior Scientist in the program in Neurosciences & Mental Health at the Hospital for Sick Children. He holds a Canada Research Chair in Cognitive Neurobiology, and is appointed as a Full Professor in the Department of Psychology, Department of Physiology and Institute of Medical Science at the University of Toronto. He is also a fellow of the Canadian Institute for Advanced Research (CIFAR) in the program for Child and Brain Development. His research focuses on modeling cognitive function and dysfunction in genetically-engineered mice. In these studies he hopes to characterize the roles of different proteins in neuronal plasticity, how different brain regions contribute to distinct cognitive processes, and how these are altered in disease states. 


Scientific focus :

The general goal of our research program is to understand how our brains normally encode, store and retrieve information. By combining mouse-genetic, molecular biology, immunohistochemical and behavioral approaches we currently focus on two major questions:

  • First, to understand how memories are initially encoded in the hippocampus, and, in particular, how adult neurogenesis might contribute to this process.
  • Second, to understand how these memories are subsequently transformed into lifelong (or remote) memories in the cortex for long-term storage.

Understanding how these basic processes work is an essential stepping stone in developing more effective treatment strategies for memory dysfunction, whether associated with normal aging, disorders such as Alzheimer’s disease, or resulting from stroke or trauma