Nonlinear regulation of unitary synaptic signals by CaV(2.3) voltage-sensitive calcium channels located in dendritic spines.
The roles of voltage-sensitive sodium (Na) and calcium (Ca) channels located on dendrites and spines in regulating synaptic signals are largely unknown. Here we use 2-photon glutamate uncaging to stimulate individual spines while monitoring uncaging-evoked excitatory postsynaptic potentials (uEPSPs) and Ca transients. We find that, in CA1 pyramidal neurons in acute mouse hippocampal slices, CaV(2.3) voltage-sensitive Ca channels (VSCCs) are found selectively on spines and act locally to dampen uncaging-evoked Ca transients and somatic potentials. These effects are mediated by a regulatory loop that requires opening of CaV(2.3) channels, voltage-gated Na channels, small conductance Ca-activated potassium (SK) channels, and NMDA receptors. Ca influx through CaV(2.3) VSCCs selectively activates SK channels, revealing the presence of functional Ca microdomains within the spine. Our results suggest that synaptic strength can be modulated by mechanisms that regulate voltage-gated conductances within the spine but do not alter the properties or numbers of synaptic glutamate receptors.
Bloodgood
Brenda L
BL
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Sabatini
Bernardo L
BL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000502:physiology*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000502:physiology*; D049229:Dendritic Spines / Q000378:metabolism*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013696:Temperature
C498916:Cacna1e protein, mouse; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D051640:Small-Conductance Calcium-Activated Potassium Channels; D015222:Sodium Channels; D002118:Calcium