NEURAL CIRCUITS AND BEHAVIOR 
Larry W. Swanson, Ph.D., Investigator 
The long-range goal of Dr. Swanson's laboratory 
is to clarify the functional organization of neural 
circuits that underlie changes in behavioral state. 
The approach has been first to define, with axonal 
transport methods, specific pathways in the rat cen- 
tral nervous system, and to examine the regulation 
of neurotransmission within specific components 
of this circuitry, using techniques for the cellular lo- 
calization of transmitters, hormones, and receptors, 
as well as their respective mRNAs. Current studies 
are based on a comparison of circuits mediating 
three interrelated classes of behavior essential for 
survival of the individual and the species. These in- 
clude drinking behavior (thirst) with associated car- 
diovascular regulation, eating behavior (hunger) 
with associated regulation of metabolism, and re- 
productive behavior and physiology. Two parts of 
the forebrain, the hypothalamus and limbic region, 
appear to play a fundamental role in mediating 
these behavioral and physiological responses, al- 
though unifying principles underlying their devel- 
opment and mature functional organization remain 
to be elaborated. 
I. Reproductive Behavior. 
Olfactory, and in particular pheromonal, informa- 
tion plays an important role in modulating repro- 
ductive physiology and behavior. Previous work in 
the laboratory showed that three cell groups, the 
posterodorsal medial nucleus of the amygdala, the 
encapsulated part of the bed nucleus of the stria 
terminalis, and the central part of the medial pre- 
optic nucleus, appear to relay pheromonal informa- 
tion and contain many estrogen-concentrating neu- 
rons. Further work also showed that estrogen 
dramatically influences levels of the neuropeptide 
cholecystokinin (CCK) in all three cell groups in 
the female rat. 
Double-immunostaining methods have now 
shown that many CCK-expressing neurons in these 
three cell groups also synthesize substance P (SP) 
and that estrogen influences CCK but not SP levels. 
Furthermore, in situ hybridization methods have 
been used to demonstrate that these effects of es- 
trogen are accompanied by changes in levels of 
mRNA for CCK but not SP Therefore estrogen ap- 
pears to alter the ratios of CCK and SP mRNA and 
peptide within pheromonal sensory pathways to 
the hypothalamus. Since this effect was observed in 
intact cycling female animals, it appears to occur 
under physiological conditions. These results sup- 
port the hypothesis that steroid hormones may 
effect a form of "biochemical switching" in anatomi- 
cally fixed circuitry related to hypothalamic-medi- 
ated reproductive and ingestive behaviors. 
A series of detailed cyto- and chemoarchitectonic 
studies was also carried out to subdivide the bed 
nuclei of the stria terminalis. This complex region 
adjacent to the hypothalamus is known from func- 
tional studies to play a key role in motivated behav- 
ior but has never been examined thoroughly. The 
results indicated that it can be divided into some 15 
clearly distinct cell groups, whose connections 
must now be examined. 
n. Neuronal Nicotinic Receptors. 
Work during the last year has continued to char- 
acterize and localize neuronal nicotinic acetyl- 
choline receptors (NAChRs) in the mammalian 
brain. It is clear from work at The Salk Institute 
that neuronal NAChRs are distinct from muscle and 
electric organ NAChRs. Neuronal receptors appear 
to consist only of a- (agonist-binding) and (3- (non- 
agonist-binding) subunits, and these subunits 
are derived from different genes than muscle a- and 
P-subunits. In collaborative studies with Drs. Jim 
Patrick and Steve Heinemann and their colleagues, 
the neuronal and a^^-subunits were character- 
ized, and their distribution throughout the cen- 
tral nervous system was studied using in situ 
hybridization. The results indicate that the p^- 
subunit is expressed in virtually every part of the 
brain and spinal cord, although the abundance 
varies widely in different cell groups. On the other 
hand, each a-subunit displays a unique, more 
restricted pattern of expression, although some 
areas clearly express more than one a-subunit. 
Additional subunits are being characterized, along 
with cloned subunits of the neuronal a-bunga- 
rotoxin-binding protein (in collaboration with Dr. 
Jon Lindstrom). 
III. Transcription Factors. 
A major goal of the laboratory is to clarify mecha- 
nisms underlying the influence of hormones on 
neuropeptide- and neurotransmitter-related recep- 
tors in circuits underlying motivated behavior. Dur- 
Continued 
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