The Role of State-Dependent Thalamocortical Communication in Visual System Plasticity

[摘要] Sleep is a phylogenetically conserved state of unconsciousness that plays a critical role in cognitive processing and underlying synaptic plasticity. However, the mechanism through which sleep contributes to brain function remains a mystery. During non-Rapid Eye Movement (non-REM) sleep, coordinated firing of neurons in the thalamocortical circuit of the brain generate oscillations characteristic of this sleep stage. These oscillations have been correlated with increases in memory retention and learning in a number of animal models. My dissertation examines the role of this state-specific thalamocortical activity in mediating sleep-dependent synaptic plasticity within the mouse visual circuit – orientation specific response potentiation (OSRP).Orientation-Specific Response Potentiation (OSRP) is a form of plasticity that takes place in adult mice after exposure to an oriented grating stimulus. OSRP occurs at thalamocortical synapses between the visual thalamus (LGN) and primary visual cortex (V1) and expresses as increased V1 firing to the presented stimulus. Our lab has demonstrated that OSRP is sleep-dependent. Furthermore, OSRP is positively correlated with the time spent in either rapid eye movement (REM) or non-REM (NREM) sleep.To further characterize the cortical nuances of OSRP, I examined the changes in neural activity following OSRP induction. V1 firing rates increase specifically across both NREM and REM sleep states, but not across wakefulness. Additionally, sleep differentially affects firing rates of V1 neurons, re-distributing firing rates such that sparsely-firing neurons increase their firing over sleep, while faster-firing neurons decrease their firing. Sparsely-firing neurons also fire more independently of the rest of the population, are more visually-responsive, and undergo the largest plastic changes in OSRP. Together, these data indicate re-distribution of firing may serve a functional role in sleep-dependent visual plasticity.Since OSRP occurs through thalamocortical relay it is also critical to elucidate how stimulus information is communicated to V1 during post-stimulus sleep. Using dual site LGN/V1 recordings, I found that, in contrast to V1 neurons, LGN neurons show immediate, stimulus-specific changes. Furthermore, LGN firing coherence with V1 field potentials increases at during NREM sleep, at both delta (0.5-4 Hz) and spindle (7-14 Hz) frequencies. The largest coherence increases occur in LGN neurons are the highly stimulus responsive, indicating these neurons may provide stimulus specific information to V1 during NREM sleep. However, this evidence is correlational.To characterize the necessity of NREM-specific oscillations in OSRP, a technician and I used optogenetics to state-specifically inhibit the circuitry that coordinates these oscillations. NREM-specific inhibition decreases the power and synchrony of NREM oscillations, subsequently preventing the consolidation of OSRP. Inhibition during REM and wake did not affect the oscillations or plasticity. Thus, I concluded that NREM oscillations promote the transfer of visually-specific information from LGN to V1.Together, this work sheds light on sleep’s role in brain plasticity in both an experience-specific and multi-regional manner. This thesis challenges major hypotheses in the field which argue that sleep uniformly downscales synaptic activity. V1 shows sleep-mediated, bidirectional alterations in firing – increasing the activity in experience-responsive neurons while decreasing the firing of others. Furthermore, it highlights a role for the thalamus as an active participant in cortical plasticity, rather than a simple relay for waking sensory information. Elucidating these changes opens the door for future work to explore these mechanisms in a manner that does justice to both the structure-specific and memory-specific changes that occur during sleep.

[发布机构] University of Michigan

[效力级别] Oscillation

[关键词] Thalamocortical;Oscillation;Plasticity;Sleep;Science;Neuroscience