title: Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates.
abstract: The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum.
authors.affiliation: The Krasnow Institute for Advanced Studies, George Mason University, Fairfax, Virginia; and.
authors.forename: R C
authors.initials: RC
authors.lastname: Evans
authors.forename: Y M
authors.initials: YM
authors.lastname: Maniar
authors.forename: K T
authors.initials: KT
authors.lastname: Blackwell
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D002118:Calcium
keywords: calcium; computational model; medium spiny neuron; striatum; upstates