GABAergic basal forebrain neurons that express receptor for neurokinin B and send axons to the cerebral cortex

J Comp Neurol. 2004 May 17;473(1):43-58. doi: 10.1002/cne.20087.


Neurons expressing neurokinin B (NK3) receptor in the basal forebrain region of rats were characterized histochemically by combining immunocytochemistry, in situ hybridization and retrograde labeling, and electrophysiologically by whole-cell clamp recording. NK3 receptor-immunoreactive neurons were found in the basal forebrain region including the substantia innominata, where axon terminals immunoreactive for preprotachykinin B, the precursor peptide of neurokinin B (NKB), were densely distributed. More than 90% of NK3 receptor-expressing neurons in the basal forebrain region showed signals for glutamate decarboxylase mRNA, indicating that almost all NK3 receptor-expressing neurons were gamma-aminobutyric acid (GABA)ergic neurons. On the other hand, only a few NK3 receptor-immunoreactive neurons showed immunoreactivity for choline acetyltransferase or parvalbumin in the substantia innominata, ventral pallidum, and globus pallidus, although the distribution of NK3 receptor-expressing neurons overlapped with those of cholinergic neurons and parvalbumin-positive neurons. After injection of wheat germ agglutinin into the cerebral cortex, NK3 receptor immunoreactivity was detected in about 25% of retrogradely labeled basal forebrain neurons, indicating that NK3 receptor-expressing neurons send projection fibers to the cerebral cortex. In the whole-cell clamp recording study, a selective NK3 receptor agonist evoked membrane depolarization or inward currents with decrease of input impedance in 10 of 100 cortically projecting neurons recorded in the basal forebrain region. Because NKB-producing striatal neurons send axons selectively to the basal forebrain region, the present results suggest that the release of NKB by those striatal neurons induces an inhibitory effect on cortical neurons via facilitation of GABAergic basal forebrain neurons expressing NK3 receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / physiology*
  • Calbindin 2
  • Calbindins
  • Cell Count / methods
  • Cerebral Cortex / metabolism*
  • Cholera Toxin / metabolism
  • Choline O-Acetyltransferase / metabolism
  • Glutamate Decarboxylase / metabolism
  • Immunoenzyme Techniques / methods
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Male
  • Membrane Potentials / physiology
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptide Y / metabolism
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques / methods
  • Peptide Fragments / pharmacology
  • Polypyrimidine Tract-Binding Protein / metabolism
  • Prosencephalon / cytology*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-3 / metabolism*
  • S100 Calcium Binding Protein G / metabolism
  • Somatostatin / metabolism
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology
  • Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Calbindin 2
  • Calbindins
  • Isoenzymes
  • Neuropeptide Y
  • Parvalbumins
  • Peptide Fragments
  • Receptors, Neurokinin-3
  • S100 Calcium Binding Protein G
  • Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
  • senktide
  • Polypyrimidine Tract-Binding Protein
  • Substance P
  • Somatostatin
  • gamma-Aminobutyric Acid
  • septide
  • Cholera Toxin
  • Choline O-Acetyltransferase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Pyrrolidonecarboxylic Acid