mPFC spindle cycles organize sparse thalamic activation and recently active CA1 cells during non-REM sleep

Sleep oscillations in the neocortex and hippocampus are critical for the integration of new memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood. To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; slow/delta; spindles), we recorded units and local field potentials (LFPs) simultaneously in the limbic thalamus, mPFC, and CA1 in rats. We report that the cycles of neocortical spindles provide a key temporal window that coordinates CA1 SWRs with sparse but consistent activation of thalamic units. Thalamic units were phase-locked to delta and spindles in mPFC, and fired at consistent lags with other thalamic units within spindles, while CA1 units that were active during spatial exploration were engaged in SWR-coupled spindles after behavior. The sparse thalamic firing could promote an incremental integration of recently acquired memory traces into neocortical schemas through the interleaved activation of thalamocortical cells.

mPFC Spindle Cycles Organize Sparse Thalamic Activation and Recently Active CA1 cells During non-REM Sleep

Sleep oscillations in neocortex and hippocampus are critical for the integration of new episodic memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood.To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; slow/delta; spindles), we recorded units and local field potentials (LFPs) simultaneously in the limbic thalamus, mPFC, and CA1 in rats. We report that the cycles of neocortical spindles provide a key temporal window that coordinates CA1 SWRs with sparse but consistent activation of thalamic units. Thalamic units were phase-locked to delta and spindles in mPFC, and fired at consistent lags with other thalamic units within spindles, while CA1 units that were active during spatial exploration were engaged in SWR-coupled spindles after behavior. The sparse thalamic firing could promote an incremental integration of recently acquired memory traces into neocortical schemas through the interleaved activation of thalamocortical cells.

Medial prefrontal cortical NMDA receptors regulate depression-like behavior and dictate limbic thalamus innervation

Depression is a pervasive and debilitating neuropsychiatric disorder. A single, low dose of the NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant major depressive disorder. Developing mechanistic understanding of how NMDAR antagonism alters synapse and circuit function is pivotal to developing translatable, circuit-based therapies for depression. Here using viral vectors, anatomical tracing, fMRI, and optogenetic-assisted circuit analysis, we assessed the role of the NMDAR subunit GluN2B in regulating cellular, synaptic, and circuit-level function and depression-related behavior. We demonstrate that post-developmental deletion of GluN2B from pyramidal neurons in medial prefrontal cortex enhances action potential output in a synaptic activity-dependent manner. GluN2B deletion dictates functional connectivity between mPFC and limbic thalamus but not ventral hippocampus and elicits antidepressant-like behavior. Our findings demonstrate that postsynaptic GluN2B exerts input-specific control of pyramidal neuron innervation, and identify a novel circuit for regulating depression-like behaviors in mice.

A Remindful Route through the Nucleus Reuniens

This chapter focuses on one nucleus of the limbic thalamus: the nucleus reuniens. It is important as a way station between the medial prefrontal cortex and the hippocampus. Its midline location and hypothalamic connections suggest that it could contribute to our subconscious memory functions.