TY - JOUR
T1 - Activation of pedunculopontine glutamate neurons is reinforcing
AU - Yoo, Ji Hoon
AU - Zell, Vivien
AU - Wu, Johnathan
AU - Punta, Cindy
AU - Ramajayam, Nivedita
AU - Shen, Xinyi
AU - Faget, Lauren
AU - Lilascharoen, Varoth
AU - Lim, Byung Kook
AU - Hnasko, Thomas S.
N1 - Publisher Copyright:
© 2017 the authors.
PY - 2017/1/4
Y1 - 2017/1/4
N2 - Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial selfphotostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders.
AB - Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial selfphotostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders.
KW - Dopamine
KW - Glutamate
KW - Optogenetics
KW - Pedunculopontine
KW - Reward
KW - Ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=85008925680&partnerID=8YFLogxK
UR - https://doi.org/10.1523/JNEUROSCI.3082-16.2016
U2 - 10.1523/JNEUROSCI.3082-16.2016
DO - 10.1523/JNEUROSCI.3082-16.2016
M3 - Article
C2 - 28053028
AN - SCOPUS:85008925680
SN - 0270-6474
VL - 37
SP - 38
EP - 46
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 1
ER -