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bioRxiv · 10.1101/2023.11.02.565356

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex

Hagger-Vaughan, N.·Kolnier, D.·Storm, J. F.
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Abstract

The prefrontal cortex (PFC) is important for executive functions, including attention, planning, decision-making, and memory, and is proposed by some leading theories to be crucial for consciousness. In particular, the global neuronal workspace theory proposes that PFC layer 2/3 pyramidal cells (L2/3PCs) contribute crucially to the global workspace, and hence to consciousness, due to their long-range connections to other cortical areas. Plateau potentials, periods of depolarisation with action potential firing outlasting the stimuli that induced them, have been suggested to help maintain working memory and to contribute to executive functions and consciousness. We therefore investigated plateau potentials and their mechanisms in PFC layer 2/3 pyramidal neurons. Using whole-cell somatic recordings from L2/3PCs in rat PFC brain slices, we found that the metabotropic cholinergic agonist muscarine reliably induced long-lasting plateau potentials with spiking following a train of evoked action potentials. Similar plateaus were induced by a metabotropic glutamate receptor (mGluR) agonist. Pharmacological tests suggested that these plateaus were dependent on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and required the presence of external calcium (Ca2+) and internal Ca2+ stores, but not voltage-gated Ca2+ channels. Using local Ca2+ applications, we found that the responsible Ca2+ influx is most likely distributed on the somatic and/or basal dendritic compartments rather than on the (distal) apical dendrite. We used knife cuts to disconnect apical dendrites, sometimes less than 50 {micro}m from the soma, and found that the plateaus did not depend on the distal apical dendrite, since truncated cells generated plateaus with as many spikes as control cells. These results indicate that layer 2/3PCs can generate plateau potentials with sustained spiking independently of distal apical dendrites.

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Hagger-Vaughan, N., Kolnier, D., Storm, J. F.. 2023-11-05. Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex. https://doi.org/10.1101/2023.11.02.565356

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