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Thalamofrontal (TF) dysconnectivity is one of the most consistent circuit-level abnormalities reported in patients with schizophrenia and is linked to deficits in short-term memory (STM). However, the biological mechanisms underlying TF weakening remain unclear. Here, we show that repeated adolescent N -methyl-d-aspartate receptor (NMDAR) antagonism produces STM deficits by impairing TF synaptic transmission. In mice repeatedly exposed to ketamine, STM impairment coincided with reduced release probability and attenuated short-term depression at mediodorsal thalamus (MD) → dorsomedial prefrontal cortex (dmPFC) synapses, without detectable changes in corticocortical synaptic release probabilit…

Sleep is critical for consolidating recent experiences into memories. A key mechanism underlying this process is hippocampal sharp-wave ripples (SWRs). Although SWR-dependent memory consolidation is often viewed as an "offline" process, sounds heard during sleep are processed by a highly active auditory system that projects to medial temporal lobe structures, providing a pathway by which sounds may modulate hippocampal activity. While processing salient sounds during sleep can be adaptive, whether ongoing processing of environmental sounds interferes with SWR-dependent memory consolidation remains unknown. To address this question, we recorded neural activity in the CA1 region of the hippocampus in sleeping rats and used a closed-loop system to deliver non-waking broadband noise (BBN) stimuli during or outside of SWRs. We found that BBN suppressed ripple power and reduced SWR rates. BBN delivered during SWRs (On-SWR) produced a greater reduction in ripple power than BBN delivered outside SWRs (Off-SWR). This suppression was accompanied by substantial changes in SWR-associated spiking. We next tested the influence of BBN on memory consolidation using a conditioned place preference paradigm. On-SWR BBN presentation during post-learning sleep abolished memory retention 24 h after learning while sparing memory immediately after sleep. By contrast, Off-SWR BBN weakened memory at both time points. Notably, On-SWR BBN induced a significantly larger impairment in memory 24 h after learning as compared with Off-SWR BBN. These findings suggest that exposure to noise during sleep disrupts hippocampal activity and impairs memory consolidation in a manner that depends on the timing of sounds relative to SWRs.