TY  - CHAP
M1  - Book, Section
TI  - Excitatory and Inhibitory Amino Acids
A1  - Nestler, Eric J.
A1  - Hyman, Steven E.
A1  - Holtzman, David M.
A1  - Malenka, Robert C.
PY  - 2015
T2  - Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e
AB  - The  major  excitatory  neurotransmitter  in  the  brain  is  glutamate;  the  major  inhibitory  neurotransmitter  is  γ-aminobutyric  acid  (GABA).Glutamate  receptors  comprise  two  large  families,  ligand-gated  ion  channels  called  ionotropic  receptors  and  G  protein–coupled  receptors  called  metabotropic  receptors.Ionotropic  glutamate  receptors  are  divided  into  three  classes—α-amino-3-hydroxy-5-methyl-4-isoxazole  propionic  acid  (AMPA)  receptors,  kainate  receptors,  and  N-methyl-D-aspartate  (NMDA)  receptors—which  are  named  after  synthetic  ligands  that  activate  them.  Individual  excitatory  synapses  typically  express  several  different  subtypes  of  ionotropic  glutamate  receptors  as  well  as  metabotropic  receptors.In  contrast  to  AMPA  receptors  and  kainate  receptors,  the  NMDA  receptor  has  two  important  biophysical  properties.  Because  it  is  highly  permeable  to  calcium  and  is  voltage  dependent,  it  allows  calcium  entry  only  if  the  cell  is  depolarized.AMPA  receptors  mediate  the  vast  majority  of  excitatory  synaptic  transmission  in  the  brain,  whereas  NMDA  receptors  play  an  important  role  in  triggering  synaptic  plasticity  and,  when  overactivated,  in  triggering  excitotoxicity.There  are  eight  subtypes  of  metabotropic  glutamate  receptors.  When  localized  to  the  presynaptic  terminal,  they  inhibit  neurotransmitter  release.  When  localized  to  the  postsynaptic  membrane,  they  exert  complex  modulatory  effects  through  specific  signal  transduction  cascades,  which  can  lead  to  excitatory  or  inhibitory  effects.The  most  extensively  studied  form  of  synaptic  plasticity  is  long-term  potentiation  (LTP)  in  the  hippocampus,  which  is  triggered  by  strong  activation  of  NMDA  receptors  and  the  consequent  large  rise  in  postsynaptic  calcium  concentration.  Several  other  types  of  LTP  are  widespread  in  the  nervous  system  and  are  mediated  via  distinct  mechanisms.Long-term  depression  (LTD),  a  long-lasting  decrease  in  synaptic  strength,  also  occurs  at  most  excitatory  and  some  inhibitory  synapses  in  the  brain.The  GABAA  receptor,  a  ligand-gated  chloride  channel,  and  the  GABAB  receptor,  a  G  protein–coupled  receptor,  are  the  two  major  classes  of  GABA  receptors.GABAA  receptors,  which  are  highly  heterogeneous,  mediate  the  bulk  of  inhibitory  synaptic  transmission  in  the  brain.  Many  drugs,  most  notably  benzodiazepines  and  barbiturates,  bind  to  GABAA  receptors  and  enhance  their  function.GABAB  receptors  are  localized  both  presynaptically,  where  they  inhibit  neurotransmitter  release,  and  postsynaptically,  where  they  mediate  a  slow,  inhibitory  synaptic  response.Glycine,  like  GABA,  is  an  inhibitory  neurotransmitter  that  activates  receptors  that  are  ligand-gated  chloride  channels.  It  is  critical  in  inhibitory  neurotransmission  in  the  spinal  cord  and  brainstem.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - neurology.mhmedical.com/content.aspx?aid=1105915527
ER  -