Genetic Deficiency of GABA Differentially Regulates Respiratory and Non-Respiratory Motor Neuron Development

Fogarty, Matthew J.; Smallcombe, Karen L.; Yanagawa, Yuchio; Obata, Kunihiko; Bellingham, Mark C.; Noakes, Peter G.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Central nervous system GABAergic and glycinergic synaptic activity switches from postsynaptic excitation to inhibition during the stage when motor neuron numbers are being reduced, and when synaptic connections are being established onto and by motor neurons. In mice this occurs between embryonic (E) day 13 and birth (postnatal day 0). Our previous work on mice lacking glycinergic transmission suggested that altered motor neuron activity levels correspondingly regulated motor neuron survival and muscle innervation for all respiratory and non respiratory motor neuron pools, during this period of development [1]. To determine if GABAergic transmission plays a similar role, we quantified motor neuron number and the extent of muscle innervation in four distinct regions of the brain stem and spinal cord; hypoglossal, phrenic, brachial and lumbar motor pools, in mice lacking the enzyme GAD67. These mice display a 90% drop in CNS GABA levels ( [2]; this study). For respiratory-based motor neurons (hypoglossal and phrenic motor pools), we have observed significant drops in motor neuron number (17% decline for hypoglossal and 23% decline for phrenic) and muscle innervations (55% decrease). By contrast for non-respiratory motor neurons of the brachial lateral motor column, we have observed an increase in motor neuron number (43% increase) and muscle innervations (99% increase); however for more caudally located motor neurons within the lumbar lateral motor column, we observed no change in either neuron number or muscle innervation. These results show in mice lacking physiological levels of GABA, there are distinct regional changes in motor neuron number and muscle innervation, which appear to be linked to their physiological function and to their rostral-caudal position within the developing spinal cord. Our results also suggest that for more caudal (lumbar) regions of the spinal cord, the effect of GABA is less influential on motor neuron development compared to that of glycine.


Related Articles

  • Methamphetamine Induces Low Levels of Neurogenesis in Striatal Neuron Subpopulations and Differential Motor Performance. Tulloch, I.; Afanador, L.; Baker, L.; Ordonez, D.; Payne, H.; Mexhitaj, I.; Olivares, E.; Chowdhury, A.; Angulo, J. // Neurotoxicity Research;Aug2014, Vol. 26 Issue 2, p115 

    Methamphetamine (METH) causes significant loss of some striatal projection and interneurons. Recently, our group reported on the proliferation of new cells 36 h after METH and some of the new cells survive up to 12 weeks (Tulloch et al., Neuroscience 193:162-169, ). We hypothesized that some of...

  • Neural plasticity.  // Wellness Options;2005, Issue 18, p17 

    Provides information on neural plasticity, considered a household expression in neuroscience as of 2005. Role of experience in plasticity; Application of neural plasticity in the rehabilitation of stroke patients.

  • Putting plasticity in its place. Sadowski, Josef H. L. P.; Mellor, Jack R. // Frontiers in Neuroscience;Jul2012, Vol. 6, p1 

    The authors comment on the dynamics of synaptic plasticity and the encoding of spatial information with reference to the article, "Spike-timing dependent plasticity and the cognitive map," by D. Bush and colleagues. They say that only few studies attempt to investigate how the two combine to...

  • Chronic Powder Diet After Weaning Induces Sleep, Behavioral, Neuroanatomical, and Neurophysiological Changes in Mice. Anegawa, Emiko; Kotorii, Nozomu; Ishimaru, Yuji; Okuro, Masashi; Sakai, Noriaki; Nishino, Seiji // PLoS ONE;12/2/2015, Vol. 10 Issue 12, p1 

    The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD) and a group fed with powder food (PD), and sleep...

  • Synaptic Competition Sculpts the Development of GABAergic Axo-Dendritic but Not Perisomatic Synapses. Frola, Elena; Patrizi, Annarita; Goetz, Thomas; Medrihan, Lucian; Petrini, Enrica Maria; Barberis, Andrea; Wulff, Peer; Wisden, William; Sasso√®-Pognetto, Marco // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated...

  • Multiple periods of functional ocular dominance plasticity in mouse visual cortex. Tagawa, Yoshiaki; Kanold, Patrick O.; Majdan, Marta; Shatz, Carla J. // Nature Neuroscience;Mar2005, Vol. 8 Issue 3, p380 

    The precise period when experience shapes neural circuits in the mouse visual system is unknown. We used Arc induction to monitor the functional pattern of ipsilateral eye representation in cortex during normal development and after visual deprivation. After monocular deprivation during the...

  • Dapper Antagonist of Catenin-1 Cooperates with Dishevelled-1 during Postsynaptic Development in Mouse Forebrain GABAergic Interneurons. Arguello, Annie; Yang, XiaoYong; Vogt, Daniel; Stanco, Amelia; Rubenstein, John L. R.; Cheyette, Benjamin N. R. // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family...

  • Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid. Tsai-Teng Tzeng; Huey-Jen Tsay; Luping Chang; Chia-Lin Hsu; Tzu-Hsuan Lai; Fong-Lee Huang; Young-Ji Shiao // Journal of Biomedical Science;2013, Vol. 20 Issue 1, p1 

    Background The roles of caspase 3 on the kainic acid-mediated neurodegeneration, dendritic plasticity alteration, neurogenesis, microglial activation and gliosis are not fully understood. Here, we investigate hippocampal changes using a mouse model that receive a single kainic acidintracerebral...

  • Functional Analysis of Histone Demethylase Jmjd2b on Lipopolysaccharide-Treated Murine Neural Stem Cells (NSCs). Das, Nando; Choi, Mi; Jung, Kyoung; Park, Ji; Lee, Hyung; Das, Amitabh; Kim, Seung; Chai, Young // Neurotoxicity Research;Feb2013, Vol. 23 Issue 2, p154 

    Neural stem cell (NSC) neurogenesis is the formation of new neurons by which the brain maintains its lifelong plasticity in response to extrinsic and intrinsic changes. Here, we show the effect of lipopolysaccharides (LPS) as an in vitro model of inflammation on NSCs to determine whether the...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics