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Principal Investigator: GINA G TURRIGIANO
Organization: BRANDEIS UNIVERSITY
Fiscal Year: 2024
Award: $564,875
Funding agency: National Eye Institute
Project Summary
Behavioral states such as sleep and wake profoundly affect the patterns of activity and neuromodulatory tone
within neocortical circuits, but the function of these state changes on learning and experience-dependent
plasticity remain controversial. It has been postulated that wake is when Hebbian mechanisms are engaged,
while sleep serves to homeostatically “renormalize” synaptic strengths/firing rates that were perturbed by
experience-dependent changes in the waking state. We study the homeostatic plasticity mechanisms that
stabilize firing rates and circuit function within primary visual cortex (V1), and can track this process in freely
behaving rodents. Perturbing firing through monocular visual deprivation (MD) initially suppresses firing (1-
2d MD), but firing rates then rebound to control levels over a 2 d period despite continued MD. Further, we can
perturb firing in the other direction using an MD followed by eye re-opening (ER) paradigm, and observed that
firing rates are potentiated by ER and again slowly return to baseline values. This ‘firing rate homeostasis’ is
accomplished in part through synaptic scaling up or down of excitatory synapses onto pyramidal neurons
within V1. We can follow this process in freely behaving animals cycling between natural bouts of sleep and
wake, to directly determine when the homeostatic restoration of firing occurs. In the last funding period we
made the surprising discovery that upward and downward firing rate homeostasis are oppositely regulated by
sleep and wake states: upward occurs gradually during each bout of active wake and is suppressed by sleep,
while downward is enabled by sleep and suppressed by wake. Our work reveals that sleep and wake states are
critically important for gating homeostatic plasticity, and act to segregate upward and downward homeostatic
processes into distinct behavioral states. How this is accomplished mechanistically is entirely unknown, as is
the function this segregation might serve. Here we propose to determine the features of waking/sleeping states
that enable/suppress firing rate homeostasis, and to test whether the underlying synaptic plasticity
mechanisms are themselves directly gated by sleep and wake. Finally, to gain insight into the
behavioral/functional consequences of this gating, we propose to test how sleep and wake orchestrate Hebbian
and homeostatic plasticity within V1 during a vision-dependent learning task. These experiments promise to
illuminate fundamental features of visual cortical physiology, and to shed light on the function of sleep and
wake states in coordinating synaptic plasticity during learning.
Terms: <Affect><Amblyopia><Animals><Arousal><Autoregulation><Behavior><Behavioral><Binding><Brain><Brain Nervous System><Crickets><Diminished Vision><Encephalon><Excitatory Synapse><Eye><Eyeball><Funding><Gryllidae><Homeostasis><Human><Image><Influentials><Learning><Long-Evans Rats><Low Vision><Modern Man><Molecular Interaction><NREM><Neocortex><Partial Sight><Pattern><Physiological Homeostasis><Physiology><Population><Primary visual cortex><Process><Pyramidal neuron><Reduced Vision><Resolution><Rodent><Rodentia><Rodents Mammals><Role><Sensory><Sight><Sleep><Source><Striate Cortex><Striate area><Subnormal Vision><Synapses><Synaptic><Synaptic plasticity><Testing><V1 neuron><Vision><Visual><Visual Cortex><Visual impairment><Work><area striata><basal forebrain><cholinergic><design><designing><effective therapy><effective treatment><experience><experiment><experimental research><experimental study><experiments><hippocampal pyramidal neuron><homotypical cortex><imaging><improved><in vivo><insight><isocortex><learned behavior><learning behavior><monocular><neocortical><neopallium><neural control><neural regulation><neuromodulation><neuromodulatory><neuroregulation><non rapid eye movement><non-REM><non-rapid eye movement><nonREM><nonrapid eye movement><optogenetics><permissiveness><resolutions><response><restoration><scale up><segregation><social role><synapse><theories><vision impairment><visual cortical><visual deprivation><visual function><visually impaired>