TRNPV-Dependent Failure of Thalamocortical Timing Delays the Return of Conscious Content during Early Emergence from Propofol Anaesthesia

Backround: Recovery from general anaesthesia is usually defined by return of behavioural responsiveness, but the capacity to encode new information may recover later. We hypothesised that early emergence from propofol reflects incomplete recovery of TRN gated thalamocortical timing needed for learning. Methods: PV-Cre mice received intravenous propofol until cortical EEG reached burst suppression, then infusion was stopped for spontaneous emergence. LORR and RORR indexed behavioural state. Mice were trained after RORR in inhibitory avoidance and auditory fear conditioning, with memory tested 24 h later. Thalamocortical dynamics were measured with electrophysiology using a single spindle-detection pipeline across NREM sleep, propofol anaesthesia, and post-emergence NREM. TRN PV activity was recorded with fibre photometry, suppressed chemogenetically, and examined ex vivo in the prefrontal, TRN, and thalamic circuit. Results: Training 5 to 15 min after RORR impaired learning despite restored arousal. Spindle-band dynamics remained abnormal early after emergence. TRN neurons were hyper-recruited around spindles, showed more burst-like firing, and exhibited altered spike to spindle phase coupling. Photometry showed elevated baseline but blunted stimulus- and cue-evoked TRN ^PV responses at 5 and 15 min, with partial recovery by 30 min. Chemogenetic TRN ^PV suppression worsened learning deficits. Ex vivo recordings indicated increased TRN ^PV intrinsic excitability, strengthened inhibition onto mediodorsal thalamus, and increased gain to prefrontal inputs without increased prefrontal excitatory drive, consistent with impaired top-down timing. Conclusion: Early emergence is a distinct vulnerable state in which learning lags behind arousal due to persistent TRN ^PV dependent disruption of spindle-associated thalamocortical timing.