Impact of spine localization of the synapse on dendritic microdomain spread.

(A) Schematic showing a spine, made of a spine head compartment and a spine neck compartment, placed at the center of the chosen dendritic oblique (depicted in Fig 2A). A glutamatergic synapse with colocalized NMDAR and AMPAR was placed at the center of the spine-head, with the AMPAR density adjusted such that the unitary somatic response to the synaptic activation was ~0.2 mV. Inset, Simultaneously recorded voltage responses to a single burst of the TBS stimulus (100 Hz, five pulses) at the spine head (red), spike neck (blue), center of the oblique (black) where the spine is connected and at the soma (cyan). It may be noted that the local oblique response manifests a dendritic spike (amplitude of voltage response at oblique: 59 mV), which does not propagate to the cell body (amplitude of voltage response at soma: 1 mV) owing to attenuation during its somatodendritic propagation. (B) Example voltage (top 11) and calcium (bottom 11) traces from different locations of the spine-head (red), spine-neck (blue) and dendritic shaft (black) in response to theta burst stimulus, TBS. Note that different scale bars were employed to represent calcium responses at the head/neck and the shaft. (C) Maximum values of cytosolic calcium concentration, (top), minimum value of unbound calmodulin [CaM]min (middle) and phosphorylated CaMKII concentration, [pCaMKII]max (bottom) obtained in response to TBS, recorded simultaneously at various locations of the spine head (red), spine neck (blue) and dendritic shaft (black). Grey dashed lines in the dendritic graphs represent the maximal level of the same molecular species measured at the dendritic shaft in the absence of spine (from Fig 2). (D) Kymographs depicting the spatiotemporal spread of microdomains along the biochemical signaling cascade in response to TBS. The top panels depict the voltage/molecular concentrations at the 10 spine head compartments; the middle panels depict the same at the 20 spine neck compartments; the bottom panels depict kymographs for 200 dendritic compartments, plotted as spread from the location of the spine (50 μm on either side of the spine) on the dendrite. H: Spine head, N: Spine neck. All channel conductances were assigned to their baseline values as mentioned in Fig 1. Details of parametric values (of active and passive properties in the oblique dendrite shown in Fig 2A) employed for simulations presented in this figure are provided in S1 Table.