Presynaptic modulation by metabotropic glutamate receptors varies among axonal varicosities supplied by the same axon. (Modified from (Rusakov and others 2004)).
A, A low-magnification fluorescence image of an area CA1 hippocampal interneuron (fragment) held in whole-cell mode. Acute slice, two-photon excitation (λ_x = 810 nm; Alexa Fluo 594 emission channel). Dendrite and axons are clearly distinguishable, as indicated. Scale bar, 10 μm.
B, A high-magnification fluorescence image of an axon fragment from cell depicted in A. Two varicosities are shown (denoted 1 and 2; Alexa emission channel; increased brightness in the middle of varicosity 1 implies that its size in the Z direction exceeds the axon diameter 2-3-fold). Dotted arrow, line-scan positioning. Scale bar, 2 μm.
C, Line-scan images (Ca²⁺-sensitive Fluo-4 emission channel) of the axon fragment shown in B in response to a pair of evoked action potentials (escape action currents, shown in upper traces). Left panel, control recording; right panel, 20 min following application of group III mGluR agonist L-AP4 (50 μM; average of 10 line-scans).
D, Digitized traces of line-scan images in C, as indicated. Black line, control recording; red line, L-AP4 application. No effect of L-AP4 is seen in varicosity 1 whereas it is substantial in varicosity 2.

A diagram of the presynaptic terminal depicting cellular mechanisms which contribute to the dynamics of free Ca²⁺. Cellular devices are labeled by green callouts, dynamic processes are shown in yellow callouts, and block arrows indicate the direction of action.

A diagram illustrating the dynamic range - time domain relationship for major cellular mechanisms that shape the dynamics of presynaptic Ca²⁺.
The abscissa indicates relative contribution in terms of the affected concentration range of free intra-terminal Ca²⁺ in response to a single AP (A) and repetitive APs (B).