Muscarinic amplification of fast excitation in hilar neurones and inhibition in granule cells in the guinea‐pig hippocampus.

Abstract

1. Effects of the cholinergic agonist, carbachol (CCh), or the acetylcholinesterase inhibitor, eserine, on presumed inhibitory hilar neurones and on inhibition in granule cells were studied by intracellular recording in guinea-pig hippocampal slices. 2. CCh (1-5 /1M) strongly enhanced the discharge activity of hilar neurones and spontaneous and evoked IPSPs in granule cells. 3. Eserine, in an atropine-sensitive manner, increased the excitability of hilar neurones through effects on membrane properties and on excitatory synaptic barrage. EPSPs readily triggered long-duration burst discharges. In granule cells, the amplitudes of evoked GABAA and GABAB receptor-mediated IPSPs were enhanced. 4. In the presence of eserine and antagonists for glutamatergic and GABAergic synaptic transmission, train stimulation evoked atropine-sensitive slow EPSPs. In contrast to those in granule cells, slow EPSPs in hilar neurones were invariably preceded by a strong burst-after-hyperpolarization. 5. We suggest that acetylcholine, released from septo-hippocampal fibres, amplifies fast synaptic excitation of inhibitory hilar neurones and inhibition of granule cells. In the dentate area, muscarinic receptor-mediated effects are faster than anticipated from the time course of the slow EPSP.

Modulation of Hippocampal Circuits by Muscarinic and Nicotinic Receptors

“…Thereby, ACh regulates the spread of excitatory activity within hippocampal and cortical circuits. These findings match with data from in vitro studies showing inhibition of CA1 pyramidal neurons by ACh-mediated excitation of interneurons (Benardo and Prince, 1982a ) and inhibition of DG granule cells due to muscarinic amplification of fast excitation in hilar neurons (Brunner and Misgeld, 1994 ), and more recent data from single unit recordings in the hippocampus and DG showing decreased spiking activity of pyramidal neurons and DG granule cell coinciding with a higher temporal precision of that spiking activity during optogenetic activation of cholinergic MSDB neurons (Dannenberg et al, 2015 ; Pabst et al, 2016 ). As outlined above, microdialysis studies show that cholinergic activity is low during quiet waking or slow wave sleep.…”

Expression of NGF and NT3 mRNAs in Hippocampal Interneurons Innervated by the GABAergic Septohippocampal Pathway

“…Activation of cholinergic septohippocampal afferents is known to increase NGF mRNA expression in the hippocampus (Lindefors et al, 1992, Berzaghi et al, 1993Freedman et al, 1993). The finding that acetylcholine acting through cholinergic-muscarinic receptors activates hippocampal inhibitory neurons, whereas it decreases electrical activity in principal cells (Brunner and Misgeld, 1994) is consistent with the notion that the above-mentioned NGF upregulation is mediated by hippocampal interneurons. In turn, activation of the GABAergic septohippocampal pathway is likely to downregulate NGF production in hippocampal interneurons, because GABA decreases NGF gene expression (Zafra et al, 1991).…”

Novelty and Novel Objects Increase c-Fos Immunoreactivity in Mossy Cells in the Mouse Dentate Gyrus

“…The anatomical connections of MCs suggest that they are well positioned to function in a circuit leading to novelty detection [26, 27]. Specifically, MCs receive concurrent sensory information from the EC via the PP as well as neuromodulatory inputs from the ascending brainstem-activating pathways including noradrenergic input from the locus coeruleus [65–67], serotoninergic input from the raphe nuclei [68, 69], cholinergic projections from the septum [70, 71], and additional extrinsic afferents [26, 72]. A subset of MCs has a low action potential threshold in response to PP stimulation, a characteristic particularly prominent in MCs with a dendrite in the molecular layer [27, 30].…”