Source: TUFTS UNIVERSITY submitted to NRP
THE INVOLVEMENT OF THE VMH IN MATERNAL BEHAVIOR IN RATS
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0196608
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Feb 1, 2002
Project End Date
Jan 31, 2005
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
BIOMEDICAL SCIENCES
Non Technical Summary
The experiments will use behavioral, moleculr, and anatomical approaches to identify the possible mechanisms of action of the ventromedial nucleus of the hypothalamus VMH on the inhibition of maternal behavior. Together, these studies will help elucidate the rold of the VMH in maternal behavior in virgin rats and identify the neural basis of parental care.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30138401020100%
Knowledge Area
301 - Reproductive Performance of Animals;

Subject Of Investigation
3840 - Laboratory animals;

Field Of Science
1020 - Physiology;
Goals / Objectives
How does the VMH inhibit maternal behavior? The overall hypothesis is that in inexperienced femal rats, the VMH blocks the display of maternal behavior through its inhibitory actions on the medial preoptic area (MPOA, an area considered to be crucially involved in the display of maternal behavior). Removal of this inhibition stimulates the onset of maternal behavior. Specific Aim #1 (Behavioral Studies): To determine the involvement of the VMH in the regulation of maternal behavior in estrogen-primed virgin rats. Specific Aim #2 (Molecular Studies): To characterize possible key changes in hormone receptor gene expression in the VMH and MPOA after estradiol-priming and VMH-lesioning in virgin rats. Specific Aim #3 (Anatomical Studies): Using track-tracing and double-labeling techniques, this set of studies will identify efferent projections from the VMH to the MPOA that may influence maternal behavior.
Project Methods
Using a estrogen-primed virgin rat model, we will determine the importance of the timing of the VMH lesions in the stimulation of short-latency maternal behavior (experiement 1). In addition, it will be determined whether inhibition of the VMH using reversible inactivation tools, such as TTX or GABA will stimulate the onset of maternal behavior. Using an estrogen-primed virgin rat model, we will determine the changes that occur in the hypothalamus, especially the MPOA, following NMA lesions of the VMH. ISHH will be used to measure estrogen, progesterone, and prolactin receptor mRNA expression. Using wheat germ agglutinin (a retrograde tracer) and Fos immunocytochemistry (ICC), it will be determined if the VMH cells that become activated in the presence of pups project to the MPOA in virgin rats. The last experiment will use triple-labeling techniques to investigate the mechanism by which the VMH inhibits maternal behavior.

Progress 02/01/02 to 01/31/05

Outputs
In the rat brain, the ventromedial nucleus of the hypothalamus (VMH) is involved with energy metabolism, hormone release, stress and anxiety, and female reproductive behavior. Recent evidence from our laboratory indicates that the VMH also regulates maternal behavior in virgin rats as part of an inhibitory neural circuit. Our progress period indicates that the VMH also regulates maternal behavior in pregnant rats, in addition to the dorsomedial nucleus (DMH). We also found that mRNA for progesterone receptors decrease in the brain at the later stage of pregnancy, while the mRNA for estrogen receptors remain unchanged. Further results indicate that the GABAergic system may not be involved with the inhibitory circuit. These data shed light on the important modifications that occur in the female brain as she changes from being non-parental to parental at parturition. In other words, what natural neurobiological events control both female disinterest and interest in young? This unusual plasticity that underlies normal physiological development - as well as the development of maternal behavior - provides an interesting model that will contribute more broadly to an understanding of both natural and unnatural behavioral responses in rats and other mammals, including humans.

Impacts
The results of these studies have implications for how a virgin female makes the transition from nulliparous (nonmaternal) to pregnant to parous (immediately maternal). Little is known of the mechanisms that exist initially to suppress or inhibit the display of maternal behavior. Our findings have added to our understanding of the normal interplay between the areas in the brain that are involved in the regulation of maternal behavior.

Publications

  • Mann, P.E. and Babb, J.A. Neurotoxic lesions of the hypothalamus advance the onset of maternal behavior in primigravid rats. Mother and Infant: Perinatal Influences on Health, 2003, Montreal, Canada.
  • Mann, P.E. and Babb, J.A. Neurotoxic lesions of the dorsomedial and ventromedial nuclei of the hypothalamus advance the onset of maternal behavior in primigravid rats. Soc. Neuroscience Abstracts, 2003, 29, San Diego, CA.
  • Mann, P.E. and Babb, J.A. Hormone receptor mRNA expression during late pregnancy in rats. Soc. Neuroscience Abstracts, 2004, 30, New Orleans, LA.
  • Mann, P.E. and Bridges, R.S. Progesterone metabolites and the inhibition of maternal behavior in primigravid rats: a possible role for neurosteroids? Soc. Neuroscience Abstracts, 2005, 31, Washington, D.C.
  • Mann, P.E. and Babb, J.A. Disinhibition of maternal behavior following ventromedial hypothalamic lesions in virgin rats, 2004, 1025, 51-58.
  • Mann, P.E. and Babb, J.A. Neural steroid hormone expression in pregnant rats. Accepted for publication with minor revisions, Molecular Brain Research, 2005.


Progress 01/01/03 to 12/31/03

Outputs
As of now, the following experiments were performed: 1) The objective of the first experiment was to determine whether the timing of VMH neurotoxic lesions is crucial for the display of fast latency maternal behavior in estrogen-primed, ovariectomized, virgin rats. The results indicate that only a 7-day interval between lesion and maternal behavior testing stimulated fast-latency maternal behavior. Determining the timing between neural insult and the change in subsequent behavior has significant impact on future experimental planning and helps in understanding the underlying neural mechanism involved. 2) The objective of this experiment was to determine if chronic infusions of the neurotransmitter gamma amino-butyric acid (GABA) would stimulate fast latency maternal behavior in ovariectomized, estrogen-primed, virgin rats. GABA infusions failed to stimulate a rapid onset maternal behavior, although there was a trend at the highest dose. In addition, GABA infusions did not affect the percentage of females responding maternally on each test day, although, again, there was trend for a higher percentage of females to display maternal behavior on test day 5. These results indicate that GABAergic neurons in the VMH may not be involved in the inhibition of maternal behavior in virgin rats. 3) The objective of this study was to determine if either DMH or VMH lesions would advance the onset of maternal behavior in first-time pregnant rats. The results indicate that lesioning the DMH stimulates rapid onset maternal behavior. In addition, there were significant differences in the median latencies to display maternal behavior following VMH lesions. These results demonstrate, for the first time, that both the DMH and VMH are involved in the inhibition of maternal behavior in first-time pregnant rats.

Impacts
The results of these studies have implications for how a virgin female makes the transition from nulliparous (nonmaternal) to pregnant to parous (immediately maternal). Little is known of the mechanisms that exist initially to suppress or inhibit the display of maternal behavior. Our findings have added to our understanding of the normal interplay between the areas in the brain that are involved in the regulation of maternal behavior.

Publications

  • Mann, P.E. and Babb, J.A. Neurotoxic lesions of the hypothalamus advance the onset of maternal behavior in primigravid rats. Mother and Infant: Perinatal Influences on Health, 2003, Montreal, Canada.
  • Mann, P.E. and Babb, J.A. Neurotoxic lesions of the dorsomedial and ventromedial nuclei of the hypothalamus advance the onset of maternal behavior in primigravid rats. Soc. Neuroscience Abstracts, 2003, 29, 728.7.
  • Mann, P.E. and Babb, J.A. Disinhibition of maternal behavior following neurotoxic lesions of the hypothalamus in primigravid rats. Brain Research, in press, 2004.