The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses.
Separate studies have implicated the lateral habenula (LHb) or amygdala-related regions in processing aversive stimuli, but their relationships to each other and to appetitive motivational systems are poorly understood. We show that neurons in the recently identified GABAergic rostromedial tegmental nucleus (RMTg), which receive a major LHb input, project heavily to midbrain dopamine neurons, and show phasic activations and/or Fos induction after aversive stimuli (footshocks, shock-predictive cues, food deprivation, or reward omission) and inhibitions after rewards or reward-predictive stimuli. RMTg lesions markedly reduce passive fear behaviors (freezing, open-arm avoidance) dependent on the extended amygdala, periaqueductal gray, or septum, all regions that project directly to the RMTg. In contrast, RMTg lesions spare or enhance active fear responses (treading, escape) in these same paradigms. These findings suggest that aversive inputs from widespread brain regions and stimulus modalities converge onto the RMTg, which opposes reward and motor-activating functions of midbrain dopamine neurons.
Jhou
Thomas C
TC
Behavioral Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Fields
Howard L
HL
Baxter
Mark G
MG
Saper
Clifford B
CB
Holland
Peter C
PC
D000200:Action Potentials / Q000502:physiology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D004597:Electroshock / Q000009:adverse effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016761:Oncogene Proteins v-fos; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D004298:Dopamine