Dynamics of active and inactive states in the mouse neocortex

Active and inactive states (sometimes referred to as UP and DOWN states) represent a fundamental activity pattern of neocortical networks in a range of mammalian species including mice, rats, cats and humans. They typify the activity of the brain during both deep sleep and anesthesia and are also related to key aspects of sensory processing. Our research describes for the first time the mechanism that underlies the robust rhythmic initiation of UP states that is a fundamental characteristic of these events in vivo.

HFSP Long-Term Fellow Magor Lorincz and colleagues
authored on Fri, 17 April 2015

In the absence of afferent inputs our brain generates several rhythmic oscillations which rely on a highly organized spatiotemporal structure characteristic of cortical circuits. The most profound oscillation present during quiet wakefulness, sleep and anesthesia is the slow (<1 Hz) oscillation which relies on rhythmic alternation of periods of synchronous neuronal activity referred to as UP states and disfacilitation and neuronal quiescence or DOWN states. The network mechanisms underlying this activity are not fully understood, but synaptic interactions between excitatory and inhibitory neocortical neurons play a key role in its generation.

In our paper we establish a fully physiologically-validated approach to studying UP/DOWN states in acute brain slices that fully recapitulates all aspects of UP/DOWN states observed in vivo, including robust rhythmicity. Using this approach we show that rhythmicity is driven by a specialized subset of slowly bursting layer 5 pyramidal neurons which we call ‘network drivers’. In addition to ‘network driver’ neurons we characterized the activity of various other neocortical cells including pyramidal and non-pyramidal neurons. Some regular spiking pyramidal neurons termed ‘early firing’ neurons were found to fire earlier than any other neuron recorded during the initiation of network activity. Our results highlight the importance of intrinsic neuronal properties in the generation of synchronized oscillations.


A Distinct Class of Slow (∼0.2–2 Hz) Intrinsically Bursting Layer 5 Pyramidal Neurons Determines UP/DOWN State Dynamics in the Neocortex. Magor L. Lőrincz, David Gunner, Ying Bao, William M. Connelly, John T.R. Isaac, Stuart W. Hughes and Vincenzo Crunelli (2015) The Journal of Neuroscience, 35(14): 5442-5458; doi: 10.1523/JNEUROSCI.3603-14.2015.

Pubmed link

Link to Journal of Neuroscience article