Document text
Principal Investigator: Isaac Cervantes Sandoval
Organization: GEORGETOWN UNIVERSITY
Fiscal Year: 2024
Award: $328,297
Funding agency: National Institute of General Medical Sciences
Summary
Learning and memory storage is a complex process that has proven challenging to tackle. Despite significant
progress in understanding classical conditioning, it is likely that in nature, the instructive value of reinforcing
experiences is acquired rather than innate. In other words, many of our learning experiences occur by inferring
value from a previously associative structure of the environment and not by the mere contiguity of conditioned
and unconditioned. This is relevant because the association between seemingly neutral stimuli expands the
gamut of possibilities to create meaningful associations and generalizations and increases the predictive power
of moment-by-moment experiences. High-order conditioning falls within this category of learning. This proposal
aims to understand the biological basis of olfactory sensory preconditioning, a form of high-order
conditioning. Specifically, we will use behavioral and functional imaging techniques combined with neuronal
and genetic manipulations, including optogenetics, to define the basic rules and dynamics of sensory
preconditioning. We will also test the dopamine modulation’s role in this form of learning. Finally, we will test the
hypothesis that olfactory representations are altered during sensory preconditioning and that this altered
representation is fundamental for forming associations between valueless stimuli. The long-term goal of this
proposal is to gain knowledge on the biological basis of how our brain achieves sensory
preconditioning.
This proposal is highly significant because there is a big gap in our knowledge of biological basis of high-order
conditioning. In addition, understanding how memories are encoded and disrupted in brain disorders is a
prerequisite to the rational design of treatments for memory impairment. Our understanding of memory formation
is based heavily on classical conditioning research. Nevertheless, we argue that high-order conditioning is
more relevant than Pavlovian association in real naturalistic situations. The results of the present studies
will provide guideposts for future research into the neurobiology of memory formation during high-order
conditioning. The project will support our long-term goal of understanding memory down to the single-cell and
subcellular levels, contributing to the knowledge base necessary for the rational development of novel treatments
for memory impairment.
Terms: <Animals><Appetite><Association Learning><Associative Learning><Behavior Control><Behavioral><Behavioral Manipulation><Biological><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><Calcium><Categories><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Circulatory Collapse><Cognitive Retention Disorders><Complex><Conditioned Reflex><Cues><DA Neuron><Data><Desire for food><Development><Dopamine><Dopamine Receptor><Dopamine neuron><Drosophila><Drosophila genus><Encephalon><Encephalon Diseases><Environment><Feedback><Flies><Functional Imaging><Goals><Habits><Human><Hydroxytyramine><Imaging Procedures><Imaging Technics><Imaging Techniques><Intracellular Communication and Signaling><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Knowledge><Learning><Link><Memory><Memory Deficit><Memory Disorders><Memory impairment><Modeling><Modern Man><Molecular><Mushroom Bodies><Nature><Nerve Cells><Nerve Unit><Nervous System><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurobiology><Neurocyte><Neurologic Body System><Neurologic Disorders><Neurologic Organ System><Neurological Disorders><Neurons><Odors><Output><Pavlovian conditioning><Phase><Physiologic Imaging><Policies><Predictive Value><Process><Research><Resolution><Role><Sensory><Shock><Signal Transduction><Signal Transduction Systems><Signaling><Stimulus><Structure><Synapses><Synaptic><Synaptic plasticity><System><Testing><Training><associative conditioning><base><bases><behavioral control><biologic><biological signal transduction><circulatory shock><classical conditioning><conditioned fear><conditioned response><conditioning><connectome><developmental><dopaminergic neuron><experience><experiment><experimental research><experimental study><experiments><falls><fear conditioning><fly><fruit fly><gene manipulation><genetic manipulation><genetically manipulate><genetically perturb><insight><intervention design><knowledge base><memory dysfunction><memory encoding><neurobiological><neurological disease><neuronal><novel><optogenetics><phase 3 evaluation><phase 3 testing><phase III evaluation><phase III testing><physiological imaging><preconditioning><rational design><resolutions><response><shocks><social role><stimulus interval><synapse><theories><therapy design><treatment design>