State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons.
Striatal medium spiny neurons (MSNs) in vivo undergo large membrane depolarizations known as state transitions. Calcium (Ca) entry into MSNs triggers diverse downstream cellular processes. However, little is known about Ca signals in MSN dendrites and spines and how state transitions influence these signals. Here, we develop a novel approach, combining 2-photon Ca imaging and 2-photon glutamate uncaging, to examine how voltage-sensitive Ca channels (VSCCs) and ionotropic glutamate receptors contribute to Ca signals in MSNs. We find that upstate transitions switch the VSCCs available in dendrites and spines, decreasing T-type while enhancing L-type channels. Moreover, these transitions change the dominant synaptic Ca source from Ca-permeable AMPA receptors to NMDA receptors. Finally, pairing bAPs with synaptic inputs generates additional synaptic Ca signals due to enhanced Ca influx through NMDA receptors. By altering the sources, amplitude, and kinetics of spine Ca signals, state transitions may gate synaptic plasticity and gene expression in MSNs.
Carter
Adam G
AG
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Sabatini
Bernardo L
BL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D020013:Calcium Signaling / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology*; D049229:Dendritic Spines / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; C082764:alpha-(4,5-dimethoxy-2-nitrobenzyl) glutamate; D013779:Tetrodotoxin; D008274:Magnesium; D002118:Calcium