title: Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity.
abstract: What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition.
authors.affiliation: Institute for Adaptive and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom.|School of Biological Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hull
authors.affiliation: School of Biological Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Soffe
authors.affiliation: Institute for Adaptive and Neural Computation, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Willshaw
authors.affiliation: School of Biological Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D019295:Computational Biology; D025461:Feedback, Physiological / Q000502:physiology*; D008954:Models, Biological; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D014981:Xenopus
chemical_list: D016202:N-Methylaspartate
references.citation: J Physiol. 1995 Dec 1;489 ( Pt 2):489-510
references.pmid: 8847642
references.citation: J Neurophysiol. 2007 Oct;98(4):2382-98
references.pmid: 17652417
references.citation: Biol Cybern. 2001 May;84(5):331-48
references.pmid: 11357547
references.citation: Prog Brain Res. 2011;188:31-50
references.pmid: 21333801
references.citation: J Neurosci. 2015 Jul 8;35(27):9799-810
references.pmid: 26156983
references.citation: J Physiol. 2012 May 15;590(10):2453-69
references.pmid: 22393253
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Aug 12;365(1551):2329-45
references.pmid: 20603355
references.citation: J Exp Biol. 1982 Aug;99:175-84
references.pmid: 7130896
references.citation: PLoS Comput Biol. 2015 May 08;11(5):e1004240
references.pmid: 25954930
references.citation: J Neurosci. 2012 Jan 11;32(2):626-38
references.pmid: 22238098
references.citation: J Neurosci. 2010 Dec 8;30(49):16609-20
references.pmid: 21148000
references.citation: J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2005 Aug;191(8):715-32
references.pmid: 15838650
references.citation: J Neurosci. 2007 Apr 25;27(17):4507-18
references.pmid: 17460064
references.citation: Eur J Neurosci. 1990;2(1):11-23
references.pmid: 12106099
references.citation: Nature. 1984 Feb 2-8;307(5950):462-5
references.pmid: 6320006
references.citation: Brain Res Brain Res Rev. 2003 Mar;41(2-3):229-67
references.pmid: 12663082
references.citation: Curr Opin Neurobiol. 1999 Dec;9(6):663-9
references.pmid: 10607645
references.citation: Prog Neurobiol. 2005 Aug;76(5):279-327
references.pmid: 16260077
references.citation: J Physiol. 1971 Feb;213(1):31-53
references.pmid: 5575343
references.citation: Front Neuroinform. 2014 Jan 28;7:47
references.pmid: 24478690
references.citation: J Physiol. 2009 Oct 15;587(Pt 20):4829-44
references.pmid: 19703959
references.citation: Science. 1985 Jul 26;229(4711):402-4
references.pmid: 17795901
references.citation: Science. 1974 Jul 12;185(4146):181-3
references.pmid: 4834220
references.citation: Eur J Neurosci. 1989 Jan;1(6):561-571
references.pmid: 12106115
references.citation: J Comp Neurol. 2001 Dec 17;441(3):248-65
references.pmid: 11745648
references.citation: J Neurosci. 2002 May 15;22(10):4229-40
references.pmid: 12019340
references.citation: Nat Neurosci. 2010 Jun;13(6):731-8
references.pmid: 20473293
references.citation: Eur J Neurosci. 2003 Jul;18(2):333-43
references.pmid: 12887415
references.citation: Nat Rev Neurosci. 2009 Jul;10(7):507-18
references.pmid: 19543221
references.citation: Nat Neurosci. 2007 Apr;10(4):494-504
references.pmid: 17369822
references.citation: Exp Brain Res. 1982;48(2):209-16
references.pmid: 7173358
references.citation: J Comput Neurosci. 1998 May;5(2):209-35
references.pmid: 9617668
references.citation: Curr Opin Neurobiol. 2004 Dec;14(6):675-84
references.pmid: 15582368
references.citation: J Neurophysiol. 2008 Jul;100(1):281-91
references.pmid: 18480368
references.citation: Physiol Rev. 1996 Jul;76(3):687-717
references.pmid: 8757786
references.citation: J Physiol. 2007 Apr 15;580(Pt. 2):485-96
references.pmid: 17272351
references.citation: J Neurosci. 2006 Apr 12;26(15):4026-35
references.pmid: 16611819
references.citation: J Neurosci. 2008 Aug 20;28(34):8577-89
references.pmid: 18716217
references.citation: J Physiol. 2009 Apr 15;587(Pt 8):1677-93
references.pmid: 19221124
references.citation: Annu Rev Neurosci. 2003;26:239-66
references.pmid: 12598679
references.citation: J Comput Neurosci. 2003 Jan-Feb;14(1):55-70
references.pmid: 12435924
references.citation: Neurosci Res. 1995 Aug;23(1):1-19
references.pmid: 7501294
references.citation: J Neurosci. 1987 Dec;7(12):3953-60
references.pmid: 3694259
references.citation: J Neurosci. 2012 May 2;32(18):6220-30
references.pmid: 22553028
references.citation: Science. 1997 Nov 7;278(5340):1122-5
references.pmid: 9353193
references.citation: Eur J Neurosci. 2012 Oct;36(7):2926-40
references.pmid: 22775205
references.citation: J Comput Neurosci. 2002 Sep-Oct;13(2):143-58
references.pmid: 12215727
references.citation: J Neurophysiol. 1998 Jan;79(1):342-51
references.pmid: 9425203
references.citation: J Neurophysiol. 1983 Apr;49(4):1017-35
references.pmid: 6854355
references.citation: J Comp Physiol A. 1992 Feb;170(2):171-80
references.pmid: 1583603
references.citation: Neuron. 2013 Jan 9;77(1):129-40
references.pmid: 23312521
references.citation: J Physiol. 1998 Sep 15;511 ( Pt 3):871-86
references.pmid: 9714867
references.citation: J Physiol. 1914 Mar 31;48(1):18-46
references.pmid: 16993247
references.citation: Annu Rev Neurosci. 1985;8:233-61
references.pmid: 2984978
references.citation: Front Behav Neurosci. 2010 Jun 24;4:16
references.pmid: 20631854
references.citation: J Physiol. 1985 Jun;363:35-59
references.pmid: 2862278
references.citation: J Physiol. 1952 Aug;117(4):500-44
references.pmid: 12991237
references.citation: J Neurophysiol. 2011 May;105(5):2487-500
references.pmid: 21346204
references.citation: J Comput Neurosci. 2007 Aug;23(1):59-77
references.pmid: 17237908
references.citation: Eur J Neurosci. 2009 Jan;29(1):87-96
references.pmid: 19087162
references.citation: PLoS Comput Biol. 2007 May;3(5):e79
references.pmid: 17480115