Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex.
Nicholas Hagger-Vaughan, Daniel Kolnier, Johan F Storm
PloS one January 1, 2024 DOI: 10.1371/journal.pone.0314652
Summary
Layer 2/3 pyramidal cells in the rat prefrontal cortex exhibit a unique type of sustained depolarization, known as plateau potentials (PPs), that operates independently of the apical dendrite. Even when the dendrite was severed, these PPs persisted, driven by localized calcium application. This activity significantly altered neuron behavior and is thought to support functions like working memory and executive decision-making. The mechanisms involve metabotropic cholinergic or glutamatergic modulation and rely on specific cation channels, highlighting their potential role in consciousness and cognitive processes.
Abstract
Here we describe a type of depolarising plateau potentials (PPs; sustained depolarisations outlasting the stimuli) in layer 2/3 pyramidal cells (L2/3PC) in rat prefrontal cortex (PFC) slices, using whole-cell somatic recordings. To our knowledge, this PP type has not been described before. In particular, unlike previously described plateau potentials that originate in the large apical dendrite of L5 cortical pyramidal neurons, these L2/3PC PPs are generated independently of the apical dendrite. Thus, surprisingly, these PPs persisted when the apical dendrite was cut off (~50 μm from the soma), and were sustained by local calcium application only to the somatic and basal dendritic compartments. The prefrontal L2/3PCs have been postulated to have a key role in consciousness, according to the Global Neuronal Workspace Theory: their long-range cortico-cortical connections provide the architecture required for the "global work-space", "ignition", amplification, and sustained, reverberant activity, considered essential for conscious access. The PPs in L2/3PCs caused sustained spiking that profoundly altered the input-output relationships of these neurons, resembling the sustained activity suggested to underlie working memory and the mechanism underlying "behavioural time scale synaptic plasticity" in hippocampal pyramidal cells. The non-apical L2/3 PPs depended on metabotropic cholinergic (mAChR) or glutamatergic (mGluR) modulation, which is probably essential also for conscious brain states and experience, in both wakefulness and dreaming. Pharmacological tests indicated that the non-apical L2/3 PPs depend on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and require external calcium (Ca2+) and internal Ca2+ stores, but not voltage-gated Ca2+ channels, unlike Ca2+-dependent PPs in other cortical pyramidal neurons. These L2/3 non-apical plateau potentials may be involved in prefrontal functions, such as access consciousness, working memory, and executive functions such as planning, decision-making, and outcome prediction.