title: Neuromodulation at single presynaptic boutons of cerebellar parallel fibers is determined by bouton size and basal action potential-evoked Ca transient amplitude.
abstract: Most presynaptic terminals in the brain contain G-protein-coupled receptors that function to reduce action potential-evoked neurotransmitter release. These neuromodulatory receptors, including those for glutamate, GABA, endocannabinoids, and adenosine, exert a substantial portion of their effect by reducing evoked presynaptic Ca(2+) transients. Many axons form synapses with multiple postsynaptic neurons, but it is unclear whether presynaptic attenuation in these synapses is homogeneous, as suggested by population-level Ca(2+) imaging. We loaded Ca(2+)-sensitive dyes into cerebellar parallel fiber axons and imaged action potential-evoked Ca(2+) transients in individual presynaptic boutons with application of three different neuromodulators and found that adjacent boutons on the same axon showed striking heterogeneity in their strength of attenuation. Moreover, attenuation was predicted by bouton size or basal Ca(2+) response: smaller boutons were more sensitive to adenosine A1 agonist but less sensitive to CB1 agonist, while boutons with high basal action potential-evoked Ca(2+) transient amplitude were more sensitive to mGluR4 agonist. These results suggest that boutons within brief segment of a single parallel fiber axon can have different sensitivities toward neuromodulators and may have different capacities for both short-term and long-term plasticities.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: David J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium; C108823:metabotropic glutamate receptor 4