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The Journal of Neuroscience, February 1, 2002, 22(3):959-969
Neurotransmitter Regulation of Cellular Activation and
Neuropeptide Gene Expression in the Paraventricular Nucleus of the
Hypothalamus
Rebecca L.
Cole and
Paul E.
Sawchenko
Laboratory of Neuronal Structure and Function, The Salk Institute
for Biological Studies and Foundation for Medical Research, La Jolla,
California 92037
Norepinephrine (NE), glutamate (Glu), and GABA have been identified
as important neurotransmitters governing neuroendocrine mechanisms
represented in the paraventricular nucleus of the hypothalamus (PVH).
Microinjection studies were used to compare the efficacy of these
transmitter mechanisms in stimulating PVH output neurons. Local
administration of NE provoked an increase in plasma corticosterone levels and Fos induction in the both the parvocellular and
magnocellular divisions of the nucleus. This treatment also stimulated
a robust increase in corticotropin-releasing factor (CRF)
heteronuclear (hn) RNA in the parvocellular PVH and a more subtle,
although reliable, increase in arginine vasopressin (AVP) hnRNA
in this same compartment. Local administration of the GABAA
receptor antagonist bicuculline methiodide (BMI) resulted in increased
plasma corticosterone and, in contrast to NE treatment, Fos induction
limited primarily to the parvocellular PVH. BMI elicited marked
increases in both CRH and AVP hnRNAs within the parvocellular division
of the nucleus. Over a wide range of concentrations, Glu failed to
produce reliable increases in corticosterone secretion and induced only
weak activational responses limited primarily to non-neurosecretory
regions of the PVH. Local Glu administration did, however, provoke Fos
induction in identified GABAergic neurons immediately adjoining the
PVH, suggesting that the muted response to Glu may be a consequence of
concurrent activation of local inhibitory interneurons. These results
support a differential involvement of adrenergic, glutamatergic and
GABAergic mechanisms in regulating neurosecretory populations of the
PVH and suggest that involvement of local circuit neurons must be
carefully considered in the interpretation of microinjection studies.
Key words:
corticotropin-releasing factor; GABA; glutamate; norepinephrine; stress; vasopressin
Copyright © 2002 Society for Neuroscience 0270-6474/02/223959-11$05.00/0
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