Serotonin Attenuates Feedback Excitation onto O-LM Interneurons

Abstract

The serotonergic system is a subcortical neuromodulatory center that controls cortical information processing in a state-dependent manner. In the hippocampus, serotonin (5-HT) is released by ascending serotonergic fibers from the midbrain raphe nuclei, thereby mediating numerous modulatory functions on various neuronal subtypes. Here, we focus on the neuromodulatory effects of 5-HT on GABAergic inhibitory oriens lacunosum-moleculare (O-LM) cells in the hippocampal area CA1 of the rat. These interneurons are thought to receive primarily local excitatory input and are, via their axonal projections to stratum lacunosum-moleculare, ideally suited to control entorhinal cortex input. We show that 5-HT reduces excitatory glutamatergic transmission onto O-LM interneurons. By means of paired recordings from synaptically connected CA1 pyramidal cells and O-LM interneurons we reveal that this synapse is modulated by 5-HT. Furthermore, we demonstrate that the reduction of glutamatergic transmission by serotonin is likely to be mediated via a decrease of calcium influx into presynaptic terminals of CA1 pyramidal cells. This modulation of excitatory synaptic transmission onto O-LM interneurons by 5-HT might be a mechanism to vary the activation of O-LM interneurons during ongoing network activity and serve as a brain state-dependent switch gating the efficiency of entorhinal cortex input to CA1 pyramidal neurons.

Generation of Sharp Wave-Ripple Events by Disinhibition

“…For the connectivity from and to anti-SWR cells, we choose the values: , and p BA = 0.6. These values are in line with experiments showing that the connectivities between principal cells and interneurons, as well as connectivities among interneurons, are distributed in the range 0%-90%: for hippocampus ( Böhm et al, 2015 ; Kohus et al, 2016 ; Pelkey et al, 2017 ; Booker and Vida, 2018 ); for neocortex ( Kwan and Dan, 2012 ; Walker et al, 2016 ; Riedemann, 2019 ). Future information about the identity of anti-SWR cells will help refining the connectivity values.…”

“…Another prominent plasticity mechanism is the short-term facilitation at synapses connecting pyramidal cells to different types of interneurons ( Reyes et al, 1998 ; Wierenga and Wadman, 2003 ; Silberberg and Markram, 2007 ; Pala and Petersen, 2015 ; English et al, 2017 ; Nanou et al, 2018 ). In the hippocampus, this mechanism has been mostly investigated for oriens-lacunosum-moleculare cells ( Ali and Thomson, 1998 ; Losonczy et al, 2002 ; Böhm et al, 2015 ). Although the identity of anti-SWR cells is currently unknown, this property could be nevertheless interesting to consider in the network.…”

Voltage Dependence of a Neuromodulator-Activated Ionic Current

“…Neuromodulators enhance the flexibility of neural networks by multiple mechanisms. These include the regulation of intrinsic properties (i.e., pre-existing conductances; Benson and Levitan, 1983 ; Kiehn and Harris-Warrick, 1992a , b ; Harris-Warrick et al, 1995 ; Galbavy et al, 2013 ), modulating synaptic properties ( Johnson et al, 1993a , b,1995 ; Zhao et al, 2011 ; Bitencourt et al, 2015 ; Böhm et al, 2015 ), reconfiguring participating neurons within the network ( Hooper and Moulins, 1989 ; Fénelon et al, 1998 ; Lieske et al, 2000 ), and modulating plasticity and even modulation itself ( Mesce, 2002 ; McLean and Sillar, 2004 ; Zhou et al, 2007 ; Pawlak et al, 2010 ; Lawrence et al, 2015 ). Another important mechanism of the regulation of neuronal excitability is the modulation of leak currents ( Bayliss et al, 1992 ; Erxleben et al, 1995 ; Talley et al, 2000 ; Cymbalyuk et al, 2002 ; Xu et al, 2009 ), and of the ratio of leak current to pacemaking current amplitude (and not just the pacemaking current amplitude), as is the case in the regulation of pacemaking activity in the pre-Bötzinger complex ( Del Negro et al, 2002 ).…”

Deciphering how interneuron specific 3 cells control oriens lacunosum-moleculare cells to contribute to circuit function

“…For example, experimental cholinergic modulation has previously been shown to switch the PRC in L2/3 pyramidal neurons from type II to type I (58), which would have synchronization consequences, and cholinergic inputs are known to be cell-specific (59). Other types of inputs to OLM cells have been reported previously, including serotonergic receptors (60), metabotropic glutamate receptors (61, 62), cholinergic receptors (63–65), additional nuances in NMDA/AMPA/Kainate receptors (66, 67), and TRPV1 receptors (68). However, in the absence of particular constraints, we opted to not include them at this time.…”