title: Not GABA but glycine mediates segmental, propriospinal, and bulbospinal postsynaptic inhibition in adult mouse spinal forelimb motor neurons.
abstract: The general view is that both glycine (Eccles, 1964) and GABA (Curtis and Felix, 1971) evoke postsynaptic inhibition in spinal motor neurons. In newborn or juvenile animals, there are conflicting results showing postsynaptic inhibition in motor neurons by corelease of GABA and glycine (Jonas et al., 1998) or by glycine alone (Bhumbra et al., 2012). To resolve the relative contributions of GABA and glycine to postsynaptic inhibition, we performed in vivo intracellular recordings from forelimb motor neurons in adult mice. Postsynaptic potentials evoked from segmental, propriospinal, and bulbospinal systems in motor neurons were compared across four different conditions: control, after gabazine, gabazine followed by strychnine, and strychnine alone. No significant differences were observed in the proportion of IPSPs and EPSPs between control and gabazine conditions. In contrast, EPSPs but not IPSPs were recorded after adding strychnine with gabazine or administering strychnine alone, suggesting an exclusive role for glycine in postsynaptic inhibition. To test whether the injected (intraperitoneal) dose of gabazine blocked GABAergic inhibitory transmission, we evoked GABAA receptor-mediated monosynaptic IPSPs in deep cerebellar nuclei neurons by stimulation of Purkinje cell fibers. No monosynaptic IPSPs could be recorded in the presence of gabazine, showing the efficacy of gabazine treatment. Our results demonstrate that, in the intact adult mouse, the postsynaptic inhibitory effects in spinal motor neurons exerted by three different systems, intrasegmental and intersegmental as well as supraspinal, are exclusively glycinergic. These findings emphasize the importance of glycinergic postsynaptic inhibition in motor neurons and challenge the view that GABA also contributes.
authors: Department of Integrative Medical Biology, Section of Physiology, Umeå University, S-901 87 Umeå, Sweden.
authors: Juan
authors: http://orcid.org/0000-0002-5117-6175
authors: J
authors: Jiang
authors: Department of Integrative Medical Biology, Section of Physiology, Umeå University, S-901 87 Umeå, Sweden bror.alstermark@umu.se.
authors: Bror
authors: B
authors: Alstermark
mesh_terms: D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D011826:Radial Nerve / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D018684:Glycine Agents; D011724:Pyridazines; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D013331:Strychnine; D005998:Glycine
keywords: GABA; adult; glycine; inhibition; motor neuron; mouse
references: J Neurophysiol. 1999 Sep;82(3):1638-41
references: 10482779
references: Exp Brain Res. 1999 Nov;129(1):1-37
references: 10550500
references: J Neurophysiol. 2001 Jul;86(1):492-502
references: 11431527
references: J Physiol. 2002 May 15;541(Pt 1):123-37
references: 12015425
references: J Physiol. 1955 Nov 28;130(2):396-413
references: 13278907
references: Nat Neurosci. 2004 Jan;7(1):17-23
references: 14699415
references: J Neurophysiol. 2004 Sep;92(3):1958-62
references: 15084639
references: J Neurophysiol. 2005 Jun;93(6):3120-6
references: 15728760
references: J Neurophysiol. 2006 Jun;95(6):3674-85
references: 16495365
references: Mol Cell Neurosci. 2006 Jul;32(3):254-73
references: 16765056
references: Adv Exp Med Biol. 1991;287:421-9
references: 1722070
references: Cell Tissue Res. 2007 Oct;330(1):1-15
references: 17610086
references: Neuron. 2008 Feb 28;57(4):524-35
references: 18304482
references: J Neurosci. 2008 Jul 16;28(29):7412-25
references: 18632945
references: Cell. 2009 Oct 2;139(1):161-74
references: 19804761
references: J Physiol. 2010 Jul 15;588(Pt 14):2621-31
references: 20519320
references: Mol Neurobiol. 2012 Feb;45(1):30-42
references: 22072396
references: Front Cell Neurosci. 2012 Mar 21;6:8
references: 22461768
references: Brain Res. 1990 Oct 15;530(1):130-7
references: 2271943
references: Nature. 2014 Apr 17;508(7496):357-63
references: 24487617
references: Nature. 2014 May 1;509(7498):43-8
references: 24784215
references: Nature. 1967 Sep 30;215(5109):1502-3
references: 4293850
references: Nat New Biol. 1971 Jun 9;231(23):187-8
references: 5281199
references: Exp Brain Res. 1970;10(1):64-80
references: 5411975
references: Exp Brain Res. 1968;5(3):235-58
references: 5721753
references: Exp Brain Res. 1984;56(2):279-92
references: 6090195
references: Exp Brain Res. 1978 Jan 18;31(1):131-41
references: 639906
references: J Neurosci. 1996 Feb 1;16(3):974-82
references: 8558266
references: J Comp Neurol. 1996 Feb 12;365(3):413-26
references: 8822179
references: Science. 1998 Jul 17;281(5375):419-24
references: 9665886