Parvalbumin-Containing Interneurons in
the Basolateral Amygdala Express High
Levels of the 1 Subunit of the
GABA
A
Receptor
ALEXANDER JOSEPH MCDONALD
*
AND FRANCO MASCAGNI
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina
School of Medicine, Columbia, South Carolina 29208
ABSTRACT
The basolateral amygdala (ABL) is essential for the amnestic effects of benzodiazepines
in aversive learning tasks. Because the 1 subunit of the -aminobutyric acid (GABA)
A
receptor is critical for these amnestic actions, knowledge of the neuronal localization of this
subunit in the ABL should contribute to an understanding of the candidate neuronal mech-
anisms involved. To examine this question, we used dual-labeling immunohistochemical
techniques to study the localization of the 1 subunit in the ABL. Our results suggest that the
1 subunit of the GABA
A
receptor is localized primarily in GABAergic interneurons in the
ABL at the somal level, although the intense neuropil staining in the lateral nucleus suggests
that distal dendrites of pyramidal projection neurons in this nucleus may also contain high
levels of the 1 subunit. The great majority of 1-immunoreactive interneurons also exhibit
immunoreactivity for the 2/3 subunits of the GABA
A
receptor. Parvalbumin-positive (PV+)
interneurons are the main interneuronal subpopulation exhibiting 1 immunoreactivity, but
some calretinin-positive interneurons also express this subunit. These data suggest that
certain subpopulations of GABAergic interneurons in the ABL, especially PV+ cells, receive
a robust GABAergic innervation. Because the most likely source of this innervation is
intrinsic, these results suggest that PV+ interneurons could constitute an important com-
ponent of interneuronal networks in the ABL. These networks may be critical for the
generation of synchronized rhythmic oscillations involved in consolidation of emotional
memories. The activation of 1-containing GABA
A
receptors in the ABL by benzodiazepines
may disrupt rhythmic oscillations critical for memory consolidation. J. Comp. Neurol. 473:
137–146, 2004. © 2004 Wiley-Liss, Inc.
Indexing terms: immunocytochemistry; calcium-binding proteins; neuropeptides; inhibition
Inhibitory neurotransmission in the central nervous
system is mediated primarily by -aminobutyric acid
(GABA)
A
receptors, most of which also contain a benzodi-
azepine binding site. Each receptor is a hetero-oligomeric
chloride channel composed of five subunits. There are at
least 19 different subunits, including 6 subunits
(Sieghart et al., 1999). The subunit composition of indi-
vidual GABA
A
receptors is an important determinant of
their biophysical and pharmacological properties. Recent
behavioral studies have demonstrated that the 1 subunit
is critical for the amnestic and sedative as well as some of
the anticonvulsant actions of benzodiazepines, whereas
the 2 subunit is important for the anxiolytic and myore-
laxation effects of benzodiazepines (Rudolph et al., 1999;
Low et al. 2000). The paradigms used to demonstrate the
1-mediated amnestic effect of benzodiazepines were
aversive learning tasks whose retention can be blocked by
activation of benzodiazepine receptors in the basolateral
amygdala (ABL) (Shibata et al., 1989; Tomaz et al., 1993).
These data suggest that the ABL may be an important site
Grant Sponsor: National Institutes of Health; Grant number: NS38998.
*Correspondence to: Alexander Joseph McDonald, Department of Phar-
macology, Physiology, and Neuroscience, University of South Carolina
School of Medicine, Columbia, SC 29208. E-mail: mcdonald@med.sc.edu
Received 25 September 2003; Revised 16 December 2003; Accepted 14
January 2004
DOI 10.1002/cne.20101
Published online the week of March 29, 2004 in Wiley InterScience
(www.interscience.wiley.com).
THE JOURNAL OF COMPARATIVE NEUROLOGY 473:137–146 (2004)
© 2004 WILEY-LISS, INC.