Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

J Comp Neurol. 2013 Apr 15;521(6):1225-50. doi: 10.1002/cne.23290.

Abstract

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium-sized (15-20 μm) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold "spikelets," suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • GABAergic Neurons / chemistry
  • GABAergic Neurons / metabolism*
  • Gene Knock-In Techniques
  • Glutamate Decarboxylase / analysis
  • Glutamate Decarboxylase / biosynthesis
  • Male
  • Mice
  • Parvalbumins / analysis
  • Parvalbumins / metabolism*
  • Prosencephalon / chemistry
  • Prosencephalon / metabolism*

Substances

  • Parvalbumins
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1