Excitation



Searching Google for "nerve excitation glutamate" uncovered 590,000 references. 



    "It is by a wide margin the most abundant neurotransmitter in the vertebrate nervous system.[1] It is used by every major excitatory function in the vertebrate brain, accounting in total for well over 90% of the synaptic connections in the human brain. It also serves as the primary neurotransmitter for some localized brain regions, such as cerebellum granule cells.  
     Biochemical receptors for glutamate fall into three major classes, known as AMPA receptors, NMDA receptors, and metabotropic glutamate receptors."  

L-Glutamate Structural Formula


    "Contents
Glutamate receptors in the mammal brain

       Family                 Type         Mechanism
AMPA Ionotropic Increase membrane permeability for sodium and potassium
kainate Ionotropic Increase membrane permeability for sodium and potassium
NMDA Ionotropic, voltage gated Increase membrane permeability for calcium
metabotropic
Group I
Gq-coupled Increase IP3 and diacyl glycerol by activating phospholipase C
metabotropic
Group II
Gi/G0-coupled Decrease intracellular levels of cAMP by inhibiting adenylate cyclase
metabotropic
Group III
Gi/G0-coupled Decrease intracellular levels of cAMP by inhibiting adenylate cyclase

Glutamate exerts its effects by binding to and activating cell surface receptors.

In mammals, four families of glutamate receptors have been identified, known as AMPA receptors, kainate receptors, NMDA receptors, and metabotropic glutamate receptors.

The first three families are ionotropic, meaning that when activated they open membrane channels that allow ions to pass through.

The metabotropic family are G protein-coupled receptors, meaning that they exert their effects via a complex second messenger system.



Comparative biology and evolution 
    Glutamate functions as a neurotransmitter in every type of animal that has a nervous system, including ctenophores (comb jellies), which branched off from other phyla at an early stage in evolution and lack the other neurotransmitters found ubiquitously among animals, including serotonin and acetylcholine.[14] Rather, ctenophores have functionally distinct types of ionotropic glutamate receptors,[14] such that activation of these receptors may trigger muscle contraction and other responses.[14]

    Sponges do not have a nervous system, but also make use of glutamate for cell-to-cell signalling. Sponges possess metabotropic glutamate receptors, and application of glutamate to a sponge can trigger a whole-body response that sponges use to rid themselves of contaminants.[15]

   The genome of Trichoplax, a primitive organism that also lacks a nervous system, contains numerous metabotropic glutamate receptors, but their function is not yet known.[16]

    In arthropods and nematodes, glutamate stimulates glutamate-gated chloride channels.[citation needed] The β subunits of the receptor respond with very high affinity to glutamate and glycine.[17] Targeting these receptors has been the therapeutic goal of anthelmintic therapy using avermectins. Avermectins target the alpha subunit of glutamate-gated chloride channels with high affinity.[18] These receptors have also been described in arthropods, such as Drosophila melanogaster[19] and Lepeophtheirus salmonis.[20] Irreversible activation of these receptors with avermectins results in hyperpolarization at synapses and neuromuscular junctions resulting in flaccid paralysis and death of nematodes and arthropods.


History

    The presence of glutamate in every part of the body as a building-block for protein made its special role in the nervous system difficult to recognize: its function as a neurotransmitter was not generally accepted until the 1970s, decades after the identification of acetylcholine, norepinephrine, and serotonin as neurotransmitters.[21] The first suggestion that glutamate might function as a transmitter came from T. Hayoshi in 1952, who was motivated by the finding that injections of glutamate into the cerebral ventricles of dogs could cause them to have seizures.[21][22] Other support for this idea soon appeared, but the majority of physiologists were skeptical, for a variety of theoretical and empirical reasons.

    One of the most common reasons for skepticism was the universality of glutamate's excitatory effects in the central nervous system, which seemed inconsistent with the specificity expected of a neurotransmitter.[21] Other reasons for skepticism included a lack of known antagonists and the absence of a known mechanism for inactivation. A series of discoveries during the 1970s resolved most of these doubts, and by 1980 the compelling nature of the evidence was almost universally recognized.[21]



Searching PubMed for "nerve excitation glutamate" uncovered 479 references: 



     The Evolution of Locomotion
  
        Pre-Bilateria Locomotion  
A summary of locomotion from the Prokaryotes  through the  Porifera  .  No mention of hormones or neurotransmitters in the summaries, but a closer reading might reveal them. 

        Bilateria Locomotion 
A summary of locomotion from the Protostomes  through  Chordate Locomotion .   No mention of hormones or neurotransmitters in the summaries, but a closer reading might reveal them.

        Amphioxus     
A summary of locomotion from  Amphioxus Motor Nerves  to Amphioxus Behavior .    No mention of hormones or neurotransmitters in the summaries, but a closer reading might reveal them. 

        Lamprey    
A summary of locomotion from   Lamprey Locomotion  to  Salamander Locomotion  .     





Quick over-views of excitation pages

        Behavioral Disinhibition  
9 references focused mostly on GABA.   


        GABA Testosterone 
10 references.  Considerable variation in foci.  No mention that the "reward" is physiologically a reduction of 
GABA/Glycine Inhibition  or  Tonic Inhibition  or an increase in  Behavioral Disinhibition .  


        Ghrelin     
10 references focused mainly on appetite.  "induces feeding and locomotor activity" 


        Cerebellar Efferent Pathways  
44 references.  "... cerebellar fibers are glutamatergic ..."  

21 references.  "sensory stimulation, shows that the putative excitatory amino acid neurotransmitter directly or indirectly acts at the pattern generating circuitry within the spinal cord."  
    Neurotransmitters: L-glutamate.  
    1989
Monosynaptic excitatory amino acid transmission from the posterior rhombencephalic reticular nucleus to spinal neurons involved in the control of locomotion in Lamprey
    1994  
Role of excitatory amino acids in brainstem activation of spinal locomotor networks in larval lamprey.


    Reticulospinal Transmission
42 references.    "The results would be explained if the noradrenergic reticulospinal system was activated from the mesencephalic locomotor region."   
    "Olfactory nerve stimulation produced excitation."
    "Application of glutamate evoked depolarizations associated with a decrease in input resistance."  
    "lamprey reticulospinal neurons utilize excitatory amino acid transmission."   
    "Intracellular stimulation of single PRRN neurons produced monosynaptic excitatory postsynaptic potentials" 
    "noradrenergic reticulospinal system"  

    Diencephaloreticular Transmission   
22 references.    Mentions:   
    "glutamate ionotropic receptor antagonists", seretonin, GABA,  "GABA(A) antagonist bicuculline".   
    Otherwise, just electrical stimulation.  
    "The lamprey DLR coincides with a region referred to as the ventral thalamus"  


        Lamprey Neurotransmitters   
66 references.  
     Glutamate, aspartate, DL-homocysteate, NMDA, N-methyl-DL-aspartate (NMDLA), quisqualate, kainate, tachykinin-like peptides, excitatory amino acid (EAA) 
    "lamprey reticulospinal neurons utilize excitatory amino acid transmission."     


       Lamprey Neuromodulators    
2 references.  5-HT and nitric oxide. 


      Lamprey Neuropeptides
9 references.  Arginine vasotocin (AVT),  Substance P    
    "lamprey reticulospinal neurons utilize excitatory amino acid transmission."
    (? glutamate ?) 

        Thalamic Neurotransmitters    
23 references.  Glutamate, Aspartate, NMDA, AMPA


        Sensory Input    
6 references.   "sensory inputs initiate and modulate locomotion by activation of reticulospinal (RS) neurones"  
Nothing about neurotransmitters. 


        Predatory Behavior  
13 references.  Nothing about the endocrine system.  


        Motor Neuron Evolution   
3 references.
    "The exact mode of transmission of monosynaptic excitation 1a and supraspinal actions in mammals remains to be elucidated."  
     "a hypothesis is advanced that neurons of similar type may communicate through pure electrical junctions, whereas successive synaptic articulations between different functional groups of neurons are formed by mixed or chemical synapses."  


    Central Pattern Generators    
96 references. 
    "Metabotropic glutamate receptors enhance the production of plateaus and produce a wind-up effect whereby repeated constant depolarizing current pulses evoke progressively more spikes per pulse.  
    N-methyl-D-aspartate (NMDA) induces oscillatory properties in spinal interneurons in several species, including lamprey, frog tadpoles , and neonatal rats."  
    "... D-glutamate initiated motor output ..." This may be the answer to my long-standing question.       


    Early Behavior  
       


1991    
Primary afferents evoke excitatory amino acid receptor-mediated EPSPs
(Excitatory postsynaptic potential - Wikipedia) that are modulated by presynaptic GABAB receptors in lamprey.      
http://www.ncbi.nlm.nih.gov/pubmed/1687474  
    1.  "
The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 
    2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did.  
    3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 
     4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level.  
    5.  In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey."  
My comments:   
1.  
"It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation."   
    Although not stated explicitly, this makes it sound as though the "
presynaptic GABAB receptors" which modulate the "EEA transmission" are on the same neurons that transmit the EEAs.  
2.  I think that the term "presynaptic" probably always indicates neuromodulators rather than neurotransmitters. 
    
Please see:    Neuromodulators vs Neurotransmitters  .
3.  The distinction between "fast (touch) and slowly adapting (pressure)" primary afferent neurons echos the distinction between fast twitch and slow twitch muscles.  Is this just a coincidence, or do fast primary afferent neurons contact fast twitch muscles and slow primary afferent neurons contact slow twitch muscles?  
    
See: 
Lamprey Fast-Slow Twitch
    1180 Related citations
     Since this is the first reference I've found that discusses both excitation and inhibition, I may skim the 1180 Related citations.   But first, the next step might be to list references for the two types. 


See: 
  1975
J Physiol.    Oct;251(2):395-407.  Ringham GL
    Localization and electrical characteristics of a giant synapse in the spinal cord of the lamprey.  
   in:   Lamprey Nervous System  . 

 



Excitation   
180826 - 1039       











Comments