Muscarinic Depolarization of Layer II Neurons of the Parasubiculum

作者：Glasgow Stephen D; Chapman C Andrew^*

来源：PLos One, 2013, 8(3): e58901.

DOI：10.1371/journal.pone.0058901

The parasubiculum (PaS) is a component of the hippocampal formation that sends its major output to layer II of the entorhinal cortex. The PaS receives strong cholinergic innervation from the basal forebrain that is likely to modulate neuronal excitability and contribute to theta-frequency network activity. The present study used whole cell current- and voltage-clamp recordings to determine the effects of cholinergic receptor activation on layer II PaS neurons. Bath application of carbachol (CCh; 10-50 mu M) resulted in a dose-dependent depolarization of morphologically-identified layer II stellate and pyramidal cells that was not prevented by blockade of excitatory and inhibitory synaptic inputs. Bath application of the M-1 receptor antagonist pirenzepine (1 mu M), but not the M-2-preferring antagonist methoctramine (1 mu M), blocked the depolarization, suggesting that it is dependent on M1 receptors. Voltage-clamp experiments using ramped voltage commands showed that CCh resulted in the gradual development of an inward current that was partially blocked by concurrent application of the selective Kv7.2/3 channel antagonist XE-991, which inhibits the muscarine-dependent K+ current I-M. The remaining inward current also reversed near E-K and was inhibited by the K+ channel blocker Ba2+, suggesting that M-1 receptor activation attenuates both I-M as well as an additional K+ current. The additional K+ current showed rectification at depolarized voltages, similar to K+ conductances mediated by Kir 2.3 channels. The cholinergic depolarization of layer II PaS neurons therefore appears to occur through M-1-mediated effects on I-M as well as an additional K+ conductance.

• 出版日期2013-3-8