Michael Numan, PhD - US grants

The long-term objectives of the proposed research are to work out the neural circuitry by which the medial preoptic area (MPOA) of the rostral hypothalamus influences maternal behavior in the rat and to understand the functon of the MPOA with respect to maternal behavior. Our specific aims can be divided into three categories: To identify specific brainstem termination sites for MPOA efferents important for maternal behavior; to identify significant sources of afferent input to the MPOA important for maternal behavior; to identify the neurotransmitters used in the neural pathways important for maternal behavior. By accomplishiung these aims we take a major step toward circuitry analysis and by understanding the functions of the structures with which the MPOA interacts we gain information on the mechanism by which the MPOA influences maternal behavior. The methodology to be employed will include: examining the effects of destroying particular neural structures and pathways on the maternal behavior of rats; the use of horseradish peroxidase histochemistry to trace neural pathways that might be important for maternal behavior; examining the effects of drugs, which influence particular neurotransmitter systems, on maternal behavior; the use of immunocytochemical techniques to identify possible peptide neurotransmitters in the neural circuitry of maternal behavior. The MPOA is involved in the reproductive behavior of all vertebrates, including primates. We view our work on the rat, a typical mammal, particularly with respect to hypothalamic neural organization, as providing basic and generalizable information on the role of the MPOA in the control of the motivational aspects of maternal behavior.

WPCc 2 B Z R ! #| x HP LaserJet III HPLASEII.PRS x @ , t 0 OpX @ Courier 10cpi Courier 10cpi Bold 2 X a ? x x x , ?w x 6 X @ 8 ; X @ l ? x x x , x ` w ; X X . E . E PSQRV G t<9 % t6 <> t, Q | } r 9 ^ZY X C~ S~ P C~ X PSQVW t S s r< t6W 9319315 Numan For survival of the species, the young must be cared for until they can subsist on their own. Until recently, little research has been directed towards the elucidation of the neural mechanisms underlying parental behavior. It is now known that the preoptic area is involved in the regulation of maternal responsiveness. Destruction of this brain region prevents the display of maternal behavior, and direct local application of hormones to this region can stimulate maternal behavior. Although it is recognized that the preoptic area is important, the way in which it produces its influence over the behavior is still not known. Dr. Numan's research is directed at providing this answer. Using neuroanatomical and neurochemical techniques, he will examine the larger neural circuitry within which the preoptic area operates to mediate maternal behavior. Dr. Numan will determine the areas in the brain that project to the preoptic region, and where the preoptic area, in turn, projects to influence maternal behavior. Moreover, he will determine the neurochemicals used in the identified neural circuits. This basic research forms the beginning of our understanding of the neural substrates of maternal responsiveness. Once the biological underpinnings of normal behavior are defined, it will be possible to identify what might go wrong in the brain during abnormal parenting. It is this typ e of basic research that will eventually lead to uncovering of some of the biological causes of poor mothering such as child abuse and neglect, and disorders such as postpartum depression. ***

The proposed research explores the interaction between specific and nonspecific motivational systems in the control of maternal behavior in animals. It will explore the interactions between the medial preoptic area (MPOA) of the hypothalamus and the nucleus accumbens-ventral pallidal circuit [NA-VP circuit] in maternal behavior. Previous research has shown the specific involvement of MPOA neural circuits in the regulation of maternal behavior. In contrast, other research has indicated that the NA-VP circuit is part of a nonspecific motivational system: activity across this circuit appears to regulate an organism's responsiveness to a wide variety of biologically significant stimuli. It is proposed that when the output of the NA-VP is driven by MPOA neurons, the organism's maternal motivation is increased [if output of the NA-VP circuit were to be driven by another specific motivational system (hunger, for example), then the type of behavioral reactivity would change accordingly]. The methods that will be employed in the proposed study include: (a) intracranial injections of drugs to alter activity within the NA-VP circuit; (b) the effects of disrupting communication between MPOA and NA-VP on maternal behavior will be examined; (c) neuroanatomical procedures to define the chemical makeup of the critical neural circuits will be performed. It is predicted that connections from the MPOA to NA-VP allow infant stimuli to activate VP neurons, and that those treatments which increase VP activity will facilitate, and those that depress VP activity will disrupt, maternal behavior. This type of basic research is important because it takes a systems level approach to the neurobiology of motivation, explaning how the brain operates to control a core social motivation - maternal responsiveness. Importantly, recent fMRI work indicates that many of the brain regions we emphasize that are important in lower animals are also active in human mothers attending to infant cues.