SPINDLE-RELATED THALAMIC RETICULAR NUCLEUS DYNAMICS DIFFER BETWEEN FEAR DISCRIMINATION AND GENERALIZATION

Fearful or stressful experiences can reshape sleep and memory, yet the circuit mechanisms linking post-trauma sleep disturbances to maladaptive fear memories remain unclear. Here, we investigated how fear learning modifies non-rapid eye movement (NREM) sleep, sleep spindles, and spindle-related thalamic dynamics in mice that discriminate contexts (discriminators) versus generalize fear (generalizers).
Using contextual fear conditioning, we quantified fear memory as discrimination accuracy between the conditioned and a neutral context while chronic electrophysiological recordings tracked sleep architecture and spindle events. After conditioning, generalizers showed wake–sleep alterations distinct from those of discriminators, accompanied by reduced spindle occurrence.
To probe spindle-generating circuitry, we recorded thalamic reticular nucleus (TRN) activity and analyzed firing patterns during spindles, including phase coupling between TRN spikes and spindle oscillations. Ongoing analyses suggest that spindle-associated TRN dynamics are systematically altered in generalizers, with reduced phase-specific spiking, consistent with impaired spindle generation and/or stabilization after excessive fear.
We also examined basolateral amygdala (BLA) activity, a hub for fear processing, during post-conditioning sleep. Preliminary results indicate that TRN firing is coupled to BLA high-frequency oscillations in discriminators but not in generalizers. Finally, we are testing whether closed-loop facilitation of slow-oscillation–spindle coupling promotes context discrimination by restoring spindle expression and timing.
Together, these findings support a model in which fear learning alters spindle-dependent NREM processing through TRN-centered circuitry, highlighting a previously unrecognized circuit mechanism engaged during fear learning.