S4E1 – Niels Niethard – Neural mechanisms underpinning sleep

In this episode, we’re joined by Dr. Niels Niethard from the University of Tübingen to explore what sleep looks like at the level of cortical microcircuits — and how excitation and inhibition are dynamically reconfigured across brain states.

Niels walks us through how excitatory pyramidal neurons interact with distinct inhibitory interneuron populations, including somatostatin (SST) and parvalbumin (PV) cells. We discuss how these cell-type-specific interactions shift from wakefulness to non-REM sleep and into REM, creating fundamentally different circuit configurations across sleep stages.

We discuss how sleep spindles, slow oscillations, and REM sleep each create distinct configurations of dendritic and somatic inhibition. Niels explains how spindle timing relative to slow oscillation peaks influences synaptic plasticity and how these processes support selective memory consolidation.

The conversation also touches on his work on synaptic downscaling in cortical and hypothalamic networks, the potential link between AMPA receptor regulation and sleep pressure, and how sleep interacts with feeding-related circuits and metabolic state in mice.

This episode offers a detailed, cell-type-specific perspective on how excitation and inhibition are balanced across sleep stages, revealing the microcircuit mechanisms underlying memory, synaptic downscaling, and brain homeostasis.

Find out more about Dr. Niethard’s lab and see relevant publications below:

• Cortical circuit activity underlying sleep slow oscillations and spindles. PNAS, 2018
• Slow-wave sleep drives sleep-dependent renormalization of synaptic AMPA receptor levels in the hypothalamus. PLOS Biolology, 2024
• Cell-type specific dynamics of calcium activity in cortical circuits over the course of slow wave sleep and rapid eye movement sleep. Journal of Neuroscience, 2021

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