Dendritic NMDA Receptors Activate Axonal Calcium Channels

NMDA receptor (NMDAR) activation can alter synaptic strength by regulating transmitter release from a variety of neurons in the CNS. As NMDARs are permeable to Ca²⁺ and monovalent cations, they could alter release directly by increasing presynaptic Ca²⁺ or indirectly by axonal depolarization sufficient to activate voltage-sensitive Ca²⁺ channels (VSCCs). Using two-photon microscopy to measure Ca²⁺ excursions, we found that somatic depolarization or focal activation of dendritic NMDARs elicited small Ca²⁺ transients in axon varicosities of cerebellar stellate cell interneurons. These axonal transients resulted from Ca²⁺ entry through VSCCs that were opened by the electrotonic spread of the NMDAR-mediated depolarization elicited in the dendrites. In contrast, we were unable to detect direct activation of NMDARs on axons, indicating an exclusive somatodendritic expression of functional NMDARs. In cerebellar stellate cells, dendritic NMDAR activation masquerades as a presynaptic phenomenon and may influence Ca²⁺-dependent forms of presynaptic plasticity and release.