ABSTRACT
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 induces LTP independently of NMDA receptor activation, and surprisingly, some inhibitory inputs to the VTA also undergo NMDAR-independent LTP after a low frequency stimulation (LFS) pairing protocol.
SIGNIFICANCE STATEMENT Synaptic plasticity of inhibitory inputs onto dopamine cells in the ventral tegmental area has a major influence on the circuits implicated in addictive behaviors. The location of electrical stimulation in an acute midbrain slice dictatedthe response of inhibitory inputs to plasticity induction protocols. We describe a new form of synaptic strengthening that occurs at an opioid-sensitive input to the ventral tegmental area.
Footnotes
HHS | NIH | National Institute on Drug Abuse (NIDA) [011289]; HHS | NIH | National Institute on Drug Abuse (NIDA) [045419]
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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