We Are Our Memories. The Molecular Codes of Memory

Carl Sagan’s famous phrase “We are stardust” [see UNAM Internacional 9, p. 14] highlights that the composition of human beings at the atomic level comes from elements present in the stars that light the universe and that our origin can be inferred from there. In my case, as a neuroscientist dedicated to the study of memory, I dare to add that, besides being stardust, humans are made of memories: We are what we remember.

Decades of research indicate that living beings that have the ability to form memories are shaped by each of the experiences that they have stored cumulatively throughout their lives and that they retain as valuable information in their memory. Based on this information, organisms interact with the environment that surrounds them, which highlights that memory is a key element for survival and decision-making. Moreover, if we think about it carefully, we can say that each person’s identity is built hand in hand with their experiences or, more specifically, from experiences that for very different reasons they store in their memory. Thus, memory studies have fascinated scientists from all over the world, who have classified them according to their duration (e.g. short-term and Long-term memory) or their type (episodic, semantic, procedural memory).

In Mexico, at UNAM´s Institute of Neurobiology, the Laboratory of Molecular Codes of Memory (LCMM) uses frontier methods to study episodic memory (related to events) with the highest possible resolution, by quantifying with high precision molecular markers of neuronal activity, synaptic plasticity, and epigenetic remodeling. Our experimental approaches allow us to analyze molecular markers in synapses (the brain’s connections), neurons, and glial cells, on the order of thousands of events per second! With this analytical capability, our goal is to understand the functional, structural, and biochemical changes that occur at the neural and synaptic level in specific regions of the brain when information is encoded, stored, and retrieved after a sensory experience or learning process. In tune with UNAM’s commitment to society, we are also interested in elucidating the impact of aging on memory-related processes, with the aim of identifying mechanisms of cognitive resilience in old age, as well as to understand the cellular and molecular mechanisms that gradually lead to memory loss and, eventually, Alzheimer’s disease. The ultimate purpose of these studies is to contribute potential prevention and treatment for the mentioned disease that, it is estimated, will affect 
76 million people globally by 2030 (see https://www.alz.org/global/).

RESEARCH LINES
Located in UNAM’s Juriquilla campus, in Querétaro, the LCMM follows two main lines of research. The first part is the fact that the activation of genetic programs (the reading of DNA that leads to protein synthesis) depends on the structure of chromatin, a macromolecular complex that condenses DNA and produceschromosomes. Chromatin has two states: an open one that allows gene expression and a closed o that prevents transcription (the reading of DNA). We are currently studying whether the epigenetic changes that occur in the brain during aging (Snigdha et al., 2016) alter the activity of neurons and synapses and thus contribute to cognitive decline in old age. For this we have created the NucleuSynapse-Tag method, an innovative experimental approach developed entirely at UNAM, which allows us to study in parallel epigenetic patterns in the neuronal nucleus and mechanisms of plasticity in synapses, all from the same neuronal population.

In our second line of research, we study the functionality of synapses in animal models, including state-of-the-art transgenic mice, which facilitate the study of Alzheimer’s disease. The functional analysis of the synapse at the single-event level has been possible thanks to the FASS-LTP method (Fluorescence Analysis of Single-Synapse Long-term Potentiation) (Prieto et al., 2015), which I developed together with Doctor Carl W. Cotman during my postdoctoral stay at the University of California Irvine (UCI), United States. We currently use FASS-LTP to identify drugs that improve synaptic plasticity, the deterioration of which is the main sign associated with memory problems in patients with Alzheimer’s disease (Prieto et al., 2017).

It is important to highlight that international collaborations with the UCI, the Cleveland Clinic (United States), and the Center for Applied Medical Research (CIMA) of the University of Navarra (Spain), as well as the strengthening of internal collaborations within UNAM and with national institutions such as CINVESTAV and the National Institute of Neurology and Neurosurgery (INNN), have allowed us to develop long-range projects that have been granted with funding from national and international organizations.

Finally, let’s visualize memory for a moment as a bridge in time, a bridge that brings images and information from a past time to the present. For Octavio Paz, Mexican poet par excellence, “Memory is a present that never quite ends” (¿Águila o Sol?, 1951); hence, it can be understood as an ethereal bridge where the past and the present converge in an instant that, when it vanishes, gradually becomes asymptotic, infinite. At UNAM we have placed ourselves on that infinite bridge made of traces of memory, so we can get to know it better.

MEMORY IS A KEY ELEMENT FOR SURVIVAL AND DECISION-MAKING

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