PMC

Glutamate release activates AMPARs and NMDARs in the spine. AMPAR opening increases the potential in the spine (V_spine), enhancing current flow through NMDARs by relief of Mg²⁺ block. The local depolarization also activates a variety of VSCCs and voltage-sensitive Na⁺ channels (VSSCs) that contribute additional depolarization or Ca²⁺ entry into the spine. Ca²⁺ through Ca_V2.3 channels specifically activates SK channels that repolarize the spine and terminate NMDAR signalling. Channels whose modulation could serve as glutamate-receptor independent mechanisms of synaptic plasticity are shown in grey ().

A, image of a spiny apical dendrite filled with 5 μm Alexa Fluor-594 (red fluorescence) and the Ca²⁺ indicator 150 μm Fluo-5F (green fluorescence). B, fluorescence collected in a line scan across the spine (sp) and dendrite (den) shown in panel A during stimulation of a bAP by somatic current injection. A bAP (white trace, top) rapidly increases green fluorescence in the spine and dendrite, indicating increased [Ca²⁺] in both compartments. C, quantification of the fluorescence transients (ΔG_bAP/G_sat) in the spine head (middle) and neighbouring dendrite (bottom) evoked by a bAP (top). The continuous lines and shaded regions depict the averages ± the standard errors of the mean (s.e.m.), respectively. D, summary of the contribution of each VSCC class to the bAP-evoked Ca²⁺ transients measured in spines in response to a single bAP. The ΔG_bAP/G_sat measured in the absence (‘none’) and in the presence (‘all’) of all the VSCC antagonists is also plotted. E, as in panel D for bAP-evoked Ca²⁺ transients measured in the dendrite. # and * indicate statistically significant (P < 0.05) differences compared to control conditions (‘none’) or the condition including all VSCC blockers (‘all’), respectively.

A, 2PLSM image of a spiny region of apical dendrite of a CA1 hippocampal pyramidal neuron filled with 10 μm Alexa Fluor-594 (red fluorescence) and 300 μm of Fluo-5F (green fluorescence). B, fluorescence collected in a line that intersects the spine head (sp) and neighbouring dendrite (den) shown in panel A during glutamate uncaging onto the spine head. The arrowheads in A and B indicate the location and timing, respectively, of a 500 μs pulse of 725 nm laser light used to trigger 2-photon mediated photolysis of MNI-glutamate. The increase in green fluorescence indicates increased intracellular [Ca²⁺]. The white trace shows the uEPSP recorded simultaneously at the soma. C, uEPSP (top) and ΔG_syn/G_sat (bottom) measured in control conditions. The continuous lines and shaded regions depict the averages ± the standard errors of the mean (s.e.m.), respectively. D and E, summary of the amplitudes of the uEPSP (D) and ΔG_syn/G_sat (E) in a variety of pharmacological conditions. The effect of each antagonist was measured in absence (black bars) or in the presence of the SK antagonist apamin (red bars). *P < 0.05 for each apamin condition compared to the corresponding apamin-free condition. #P < 0.05 compared to control condition – i.e. in the absence of all antagonists.