PT - JOURNAL ARTICLE AU - Robyn St. Laurent AU - Julie Kauer TI - Synaptic Plasticity at Inhibitory Synapses in the Ventral Tegmental Area Depends upon Stimulation Site AID - 10.1523/ENEURO.0137-19.2019 DP - 2019 Nov 01 TA - eneuro PG - ENEURO.0137-19.2019 VI - 6 IP - 6 4099 - http://www.eneuro.org/content/6/6/ENEURO.0137-19.2019.short 4100 - http://www.eneuro.org/content/6/6/ENEURO.0137-19.2019.full SO - eNeuro2019 Nov 01; 6 AB - Drug exposure induces cell and synaptic plasticity within the brain reward pathway that could be a catalyst for progression to addiction. Several cellular adaptations have been described in the ventral tegmental area (VTA), a central component of the reward pathway that is the major source of dopamine release. For example, administration of morphine induces long-term potentiation (LTP) of excitatory synapses on VTA dopamine cells and blocks LTP at inhibitory synapses. Drug-induced synaptic changes have a common endpoint of increasing dopamine cell firing and dopamine release. However, gaining a complete picture of synaptic plasticity in the VTA is hindered by its complex circuitry of efferents and afferents. Most studies of synaptic plasticity in the VTA activated a mixed population of afferents, potentially yielding an incomplete and perhaps misleading view of how drugs of abuse modify VTA synapses. Here, we use midbrain slices from mice and find that electrical stimulation in two different regions induces different forms of plasticity, including two new forms of LTP at inhibitory synapses. High-frequency stimulation (HFS) induces LTP independently of NMDA receptor (NMDAR) activation, and surprisingly, some inhibitory inputs to the VTA also undergo NMDAR-independent LTP after a low-frequency stimulation (LFS) pairing protocol.