Medial septum differentially regulates dopamine neuron activity in the rat ventral tegmental area and substantia nigra via distinct pathways

Neuropsychopharmacology. 2018 Sep;43(10):2093-2100. doi: 10.1038/s41386-018-0048-2. Epub 2018 Mar 27.


The medial septum (MS) impacts hippocampal activity and the hippocampus, in turn, regulates midbrain dopamine (DA) neuron activity. However, it remains to be determined how MS activation impacts midbrain DA activity. This question was addressed by infusing NMDA (0.75 µg/0.2 µL) into the medial septum of anesthetized male Sprague-Dawley rats and recording dopamine neuron activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). MS activation increased (71%) the number of spontaneously active DA neurons in the VTA, and decreased (40%) the number of active DA neurons in the SNc. Effects in both the VTA and SNc required the ventral subiculum, but were differentially dependent on cholinergic and GABAergic mechanisms within the vSub and rostral and caudal subregions of the ventral pallidum, respectively. MS activation also decreased amphetamine-induced locomotor behavior, which was dependent on GABAergic inputs to the hippocampus. These findings demonstrate that the MS differentially regulates meso-striatal DA transmission via distinct pathways.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Central Nervous System Stimulants / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Globus Pallidus / drug effects
  • Globus Pallidus / physiology
  • Hippocampus / drug effects
  • Male
  • Motor Activity / drug effects
  • N-Methylaspartate / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Septum of Brain / drug effects
  • Septum of Brain / physiology*
  • Signal Transduction / drug effects*
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*


  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Amphetamine