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The GABA System of the Mammalian CNS

  • Eugene Roberts

Abstract

My current working models of nervous system function are based partly on many experimental observations, often supported by extensive immunocytochemical findings, and partly on their extrapolation into reasonable potentialities. Particular emphasis is placed on consideration of the roles of inhibitory GABAergic neurons in normal and abnormal information processing in the CNS. The point of view taken is that the nervous system is highly restrained, with inhibitory neurons acting like reins that serve to keep the neuronal “horses” from running away. It is proposed that in behavioral sequences, innate or learned, preprogrammed circuits are released to function at varying rates and in various combinations. This is accomplished largely by the disinhibition of pacemaker neurons whose activities are under the control of tonically active inhibitory command neurons, many of which use GABA as a transmitter. According to this view, disinhibition is permissive, and excitatory input to pacemaker neurons has mainly a modulatory role. In addition to the above restraining function, local circuit GABAergic neurons participate in processes that result in producing feedforward, feedback, surround, and presynaptic inhibition and presynaptic facilitation. Information arriving from several sources is integrated in specialized command centers such as the cerebellar cortex, the basal ganglia, and the reticular nucleus of the thalamus which, through inhibitory GABAergic neurons, exert high frequency monosynaptic tonic inhibition in various brain regions. The analysis of the inputs to the command regions is reflected, with variable time delays, in decreased frequencies of firing of appropriate combinations of their inhibitory output neurons, releasing neural activity in the direct channels to which they project, so that it becomes optimally compatible temporally and spatially with activity elsewhere in the CNS.

Keywords

Variable Time Delay Excitatory Input Presynaptic Inhibition Nervous System Function Initial Axon Segment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    E. Roberts, Epilepsy and antiepileptic drugs: A speculative synthesis, in “Antiepileptic Drugs: Mechanisms of Action,” G. H. Glaser, J. K. Penry, and D. M. Woodbury, eds., Raven Press, New York (1980).Google Scholar
  2. 2.
    E. Roberts, A speculative consideration on the neurobiology and treatment of senile dementia, in “Strategies for the Development of an Effective Treatment for Senile Dementia,” T. Crook and S. Gerson, eds., Mark Powley Associates, Inc., New Canaan, Ct., (1981).Google Scholar
  3. 3.
    E. Roberts, GABA-related phenomena, models of nervous system function, and seizures, in: “Basic Mechanisms of Epilepsy,” Ann. Neurol., (in press).Google Scholar
  4. 4.
    E. Roberts, T. N. Chase, and D. B. Tower, eds., “GABA in Nervous System Function,” Raven Press, New York, (1976).Google Scholar
  5. 5.
    J. J. Sloper, An electron microscope study of the termination of afferent connections to the primate motor cortex, J. Neurocytol., 2: 361 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    Y. Grossman, M. E. Spira, and I. Parnas, Differential flow of information into branches of a single neuron, Brain Res, 64: 379 (1973).PubMedCrossRefGoogle Scholar
  7. 7.
    E. R. Kandel and D. Gardner, The synaptic actions mediated by the different branches of a single neuron, in: “Neurotransmitters, Res. Publications Assoc. Res. in Nervous and Mental Disease,” Vol. 50, I. J. Kapin, ed., Williams and Wilkins, Baltimore, Md. (1972).Google Scholar
  8. 8.
    R. Barber, J. E. Vaughn, K. Saito, B. J. McLaughlin, and E. Roberts, GABAergic terminals are presynaptic to primary afferent terminals in the substantia gelatinosa of the rat spinal cord, Brain Res, 141: 35 (1978).PubMedCrossRefGoogle Scholar
  9. 9.
    B. E. Alger and R. A. Nicoll, Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro, J.Physiol., 328: 105 (1982).PubMedGoogle Scholar
  10. 10.
    F. E. Dudek, R. D. Andrew, B. A. MacVicar, R. W. Snow, and C. P. Taylor, Recent evidence for and possible significance of gap junctions and electrotonic synapses in the mammalian brain, in “Basic Mechanisms of Neuronal Hyper- excitability,” H. H. Jasper and N. M. van Gelder, eds., New York, Alan R. Liss (in press).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Eugene Roberts
    • 1
  1. 1.Division of NeurosciencesBeckman Research Institute of the City of HopeDuarteUSA

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