Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation

J Cereb Blood Flow Metab. 2008 Feb;28(2):221-31. doi: 10.1038/sj.jcbfm.9600558. Epub 2007 Sep 26.


Neurovascular coupling, or the tight coupling between neuronal activity and regional cerebral blood flow (CBF), seems largely driven by the local processing of incoming afferent signals within the activated area. To test if cortical gamma-aminobutyric acid (GABA) interneurons-the local integrators of cortical activity-are involved in this coupling, we stimulated the basalocortical pathway in vivo, monitored cortical CBF, and identified the activated interneurons (c-Fos-immunopositive) and the neuromediators involved in this response. Basal forebrain (BF) stimulation induced ipsilateral increases in CBF and selective activation of layers II to VI somatostatin- and/or neuropeptide Y-containing, as well as layer I GABA interneurons. Nitric oxide synthase interneurons displayed weak bilateral activation, whereas vasoactive intestinal polypeptide- or acetylcholine (ACh)-containing GABA interneurons were not activated. Selective cholinergic deafferentation indicated that ACh released from stimulated BF afferents triggered the CBF response, but the latter was mediated, in part, by the local release of GABA from cholinoceptive cortical interneurons, and through GABA-A receptor-mediated transmission. These data show that activation of specific subsets of GABA interneurons and their GABA-A-mediated effects on neuronal, vascular, and/or astroglial targets are necessary for the full expression of the hemodynamic response to BF stimulation. Further, these findings highlight the importance of understanding the cellular networks and circuitry that underlie hemodynamic signals, as only specific subsets of neurons may be activated by a given stimulus, depending on the afferent inputs they receive and integrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / physiology
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology
  • Blood Vessels / innervation
  • Blood Vessels / physiology*
  • Capillaries / metabolism
  • Cerebral Cortex / blood supply*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Denervation
  • Electric Stimulation
  • Electrophysiology
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Immunohistochemistry
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Male
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Nitric Oxide Synthase Type III / metabolism
  • Nitric Oxide Synthase Type III / physiology
  • Parasympathetic Nervous System / physiology
  • Prosencephalon / blood supply*
  • Prosencephalon / drug effects
  • Prosencephalon / physiology*
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / physiology
  • Somatostatin / metabolism
  • gamma-Aminobutyric Acid / physiology*


  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, GABA-A
  • Somatostatin
  • gamma-Aminobutyric Acid
  • Nitric Oxide Synthase Type III
  • Acetylcholine