Dendritic Calcium Nonlinearities Switch the Direction of Synaptic Plasticity in Fast-Spiking Interneurons

Abstract

Postsynaptic calcium (Ca²⁺) nonlinearities allow neuronal coincidence detection and site-specific plasticity. Whether such events exist in dendrites of interneurons and play a role in regulation of synaptic efficacy remains unknown. Here, we used a combination of whole-cell patch-clamp recordings and two-photon Ca²⁺ imaging to reveal Ca²⁺ nonlinearities associated with synaptic integration in dendrites of mouse hippocampal CA1 fast-spiking interneurons. Local stimulation of distal dendritic branches within stratum oriens/alveus elicited fast Ca²⁺ transients, which showed a steep sigmoidal relationship to stimulus intensity. Supralinear Ca²⁺ events required Ca²⁺ entry through AMPA receptors with a subsequent Ca²⁺ release from internal stores. To investigate the functional significance of supralinear Ca²⁺ signals, we examined activity-dependent fluctuations in transmission efficacy triggered by Ca²⁺ signals of different amplitudes at excitatory synapses of interneurons. Subthreshold theta-burst stimulation (TBS) produced small amplitude postsynaptic Ca²⁺ transients and triggered long-term potentiation. In contrast, the suprathreshold TBS, which was associated with the generation of supralinear Ca²⁺ events, triggered long-term depression. Blocking group I/II metabotropic glutamate receptors (mGluRs) during suprathreshold TBS resulted in a slight reduction of supralinear Ca²⁺ events and induction of short-term depression. In contrast, blocking internal stores and supralinear Ca²⁺ signals during suprathreshold TBS switched the direction of plasticity from depression back to potentiation. These data reveal a novel type of supralinear Ca²⁺ events at synapses lacking the GluA2 AMPA subtype of glutamate receptors and demonstrate a general mechanism by which Ca²⁺-permeable AMPA receptors, together with internal stores and mGluRs, control the direction of plasticity at interneuron excitatory synapses.