Cholinergic suppression of excitatory synaptic transmission in layers II/III of the parasubiculum

Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the CA1 region of the hippocampus and sends a major output to layer II of the medial and lateral entorhinal cortex. The PaS also receives heavy cholinergic innervation from the medial septum, which contributes to the generation of theta-frequency (4–12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor activation exerts a wide range of effects in other areas of the hippocampal formation, including membrane depolarization, changes in neuronal excitability, and suppression of excitatory synaptic responses. The present study was aimed at determining how cholinergic receptor activation modulates excitatory synaptic input to the layer II/III neurons of the PaS in acute brain slices. Field excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were evoked by stimulation of either layer I afferents, or ascending inputs from layer V. Bath-application of the cholinergic agonist carbachol (0.5–10 μM) suppressed the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation, and also enhanced paired-pulse facilitation. Constant bath-application of the GABAA antagonist bicuculline (10 μM) failed to eliminate the suppression, indicating that the cholinergic suppression of fEPSPs is not due to increased inhibitory tone. The muscarinic receptor antagonist atropine (1 μM) blocked the suppression of fEPSPs, and the selective M1-preferring receptor antagonist pirenzepine (1 μM), but not the M2-preferring antagonist methoctramine (1–5 μM), also significantly attenuated the suppression. Therefore, cholinergic receptor activation suppresses excitatory synaptic input to layer II/III neurons of the PaS, and this suppression is mediated in part by M1 receptor activation.

▶The parasubiculum (PaS) projects primarily to layer II of the entorhinal cortex. ▶Field EPSPs are evoked in layer II/III of the PaS by local stimulation in vitro. ▶The cholinergic agonist carbachol (CCh) suppresses PaS EPSPs via M1 receptors. ▶Paired-pulse measures suggest that CCh acts via reduced glutamate release.