The place of learning theory in psychology has fluctuated dramatically over the last few decades. At the height of the behaviourist era in the 1940s and 1950s, many people would have identified learning as the single most important topic of investigation in psychology. By the 1970s, though, the picture was very different. A large number of influential psychologists had come to regard learning theory as a sterile field that made little contact with the realities of human cognition, and instead their interest switched towards such topics as knowledge representation and inference. Lately, things have come full circle, and the expanding new field of connectionism has restored learning theory to centre stage.

My aim in this book has been to have a fresh look at learning theory. I believe that the changing fortunes of the field have occurred because psychologists have often come to the topic of learning with certain deep conceptions of the mind already in place. But I suggest that rather than seeing learning as a topic to be annexed by and interpreted in terms of whatever the current fashionable theory happens to be, it is far more profitable for traffic to flow in the opposite direction. Let us commence by asking some general questions about learning, and see what sort of mind we end up with.

Someone coming to the field of learning afresh is likely to be disconcerted by the apparent incompatibility of a number of theoretical approaches and even terminologies.

In the last chapter we established that, to a first approximation, the human learning system behaves normatively. In attempting to answer the question ‘What is the system doing?’ (the first of our three questions), we have found that associative learning corresponds reasonably well to the prescriptions of contingency theories. In reaching this conclusion, we have remained agnostic about how the system actually works; all we have shown is that the behaviour it yields in associative learning tasks is roughly what a statistician utilising the notion of contingency would prescribe. In the present chapter we begin our consideration of how the system achieves this end. Here, we ask the second question, ‘What sort of information is acquired during the course of a learning experience?’. In the next chapter, we will ask exactly how at the mechanistic level this information is acquired.

We begin by considering the phenomenon of generalisation, which represents one of the principal challenges to any theory of learning. Having learned something about one stimulus, how will acquired knowledge determine responding to some further stimulus? Generalisation is of interest not just because it is something we would like our theories of learning to explain, but also because it provides data that may tell us about the way in which information is represented. Two quite different views of the form of information underlying associative learning have been embodied in prototype and instance theories, and for these theories generalisation is a central issue. They attempt to describe how learning takes place in situations where there is considerable stimulus variation from trial to trial, and where the ability to generalise to new stimuli perceptibly different from ones already encountered is essential.

Introduction

The relationships between steroid hormones and brain function have been envisioned mostly within the framework of endocrine mechanisms, as responses elicited by secretory products of steroidogenic endocrine glands, borne by the bloodstream, and exerting actions on the brain.

In fact, the brain is a target organ for steroid hormones. Intracellular receptors involved in the regulation of specific gene transcription have been identified in neuroendocrine structures, with each class of receptor having a unique distribution pattern in the complex anatomy of the brain (Fuxe et al. 1981; McEwen 1991a). Mechanisms involving nuclear receptors account for most steroid-induced feedback and many behavioral effects, for the regulation of the synthesis of several neurotransmitters, hormone-metabolizing enzymes, and hormone and neuromediator receptors, and for the organizational effects on neural circuitry that occur during development and persist into adulthood.

Local target tissue metabolism is an important factor in the mechanism of action of sex steroid hormones. Not only might such metabolism be involved in the regulation of intracellular hormone levels, but it might also provide an essential contribution to the cellular response. The brain is a site of extensive steroid metabolism. Aromatization and 5α-reduction represent major routes of androgen metabolism (Naftolin et al. 1975; Celotti et al. 1979; McLusky et al. 1984). The importance of these two pathways lies in the fact that they give rise to metabolites with considerable biological activity and thus are involved in the mechanism by which circulating androgens influence neuroendocrine function and behavior.

Introduction

It should not have been surprising that gonadal steroids exert powerful influences on cell–cell interactions in the magnocellular hypothalamoneurohypophyseal system (HNS) of the rat, but somehow it was. Since this system is responsible for the manufacture and release of oxytocin during parturition and lactation, times when the levels of circulating gonadal steroids show dramatic variations, some steroid involvement in the functioning of HNS could have been anticipated. Perhaps such anticipation was dulled by the observation that the dynamic interactions taking place among the cells of the HNS also occurred in response to manipulations of the animal's hydrational state, which have not been associated traditionally with variations in gonadal steroid output. However, gonadal steroids appear to exert some control over the cellular mechanisms that release both oxytocin and vasopressin in response to dehydration. Estrogens and androgens, under comparable conditions, often have opposite effects on the HNS. This chapter reviews the main structure–function relationships of the HNS, the dynamics of these relationships under physiological conditions of altered peptide hormone demand, and some of the roles possibly played in these functions by gonadal steroids in both males and females.

The magnocellular HNS

The magnocellular HNS is constituted chiefly by the supraoptic (SON) and paraventricular (PVN) nuclei, accessory nuclei in the anterior hypothalamus, and the neurohypophysis or neural lobe (NL) of the posterior pituitary to which the neurons of those hypothalamic nuclei send axonal projections (Fig. 18.1).

Sexual behavior of male rodents depends heavily on the actions of testosterone and its metabolites. One means by which testosterone may facilitate copulation is by altering the release and/or effectiveness of neurotransmitters. This chapter integrates information and speculation concerning the multiple roles of one such neurotransmitter, dopamine, in the regulation of male rat sexual behavior.

The three major dopamine systems that are important for male sexual behavior, including sexual motivation and genital reflexes, will be reviewed. Then, evidence suggesting that testosterone influences dopamine activity in the medial preoptic area (MPOA) and nucleus accumbens (NAc) will be discussed. Recent results suggesting that a novel messenger molecule, nitric oxide, might affect both dopamine release and sexual behavior will be presented, as will preliminary evidence suggesting that stimulation of the D1 dopamine receptor promotes copulation-induced expression of the immediate early gene c-fos in the MPOA. Finally, a model summarizing some of the events related to central dopamine release will be described.

The problem of neural coordination of behavior

The execution of a behavior as complex as copulation requires exquisite coordination of neural activity in numerous sites. Olfactory, visual, auditory, and somatosensory stimuli elicit a precisely timed and coordinated motor sequence that includes locomotor pursuit, mounting and pelvic thrusting, penile erection and insertion, and ultimately ejaculation and postejaculatory grooming and quiescence. Steroid hormones facilitate this process by biasing sensorimotor integration, so that a sexually relevant stimulus is more likely to elicit a sexual response. Most effects of steroid hormones on sexual behavior are relatively long term.

The discovery that the hypothalamus is responsible for controlling both reproductive hormones and behavior suggested various mechanisms by which hormonal and behavioral cycles are inexorably linked, and even co-regulated. While our knowledge about this process has grown dramatically, our understanding of the essential control circuits that operate during normal reproduction, or fail in abnormal functioning, is still limited. Various neurotransmitter candidates have been proposed as essential elements of the systems that regulate reproduction. However, few are involved in so many aspects of reproduction as are the opioid peptides, which play a critical or supporting role in (a) controlling hormonal cycling in females (Akabori and Barraclough 1986; Kalra 1985; Wiesner et al. 1984), (b) regulating reproductive behavior in males (Hughes et al. 1988; Matuszewich and Dornan 1992; Myers and Baum 1979) and females (Pfaus and Pfaff 1992; Sirinathsinghji 1986; Wiesner and Moss 1986a), and even (c) modulating mesolimbic dopamine release mediated by reinforcing sexually relevant olfactory stimuli (Mitchell and Gratton 1991).

Gonadal steroid regulation of hypothalamic opioids represents an important feedback system by which to control reproduction. Hypothalamic (opioid) circuits regulate hormonal releasing hormones that control pituitary secretion. This regulation in turn affects gonadal steroid hormones, which act centrally to alter opioid function and facilitate reproductive behavior. Since such feedback is vitally important for the regulation of hormonal and behavioral events during the estrous cycle, most of this discussion will be limited to opioid action in females. Many of the experiments that we will describe utilized models of hormone manipulation to investigate natural regulation of hypothalamic opioid systems in animals, primarily rodents.

The expression of sexually differentiated patterns of behavior is a characteristic of many vertebrate species and often correlates with sex differences in the relative abundance of neurons in brain regions thought to control such behaviors. In general, two fundamental processes determine the number of neurons that survive into adulthood. First, changes in the number of neuroblasts formed in the ventricular zone can occur in response to mechanisms that are intrinsic to a particular population of cells or that are controlled by extrinsic factors such as cell–cell interactions, neuronal growth factors, and circulating hormones. Second, similar extrinsic cellular and hormonal factors can determine the number of cells of a particular lineage that reach their permanent destination, establish appropriate connections, and achieve a regionally specific functional phenotype. Sex steroid hormones can affect both processes but appear to exert their most pronounced influences on neuronal development during a restricted perinatal critical period (Arnold and Gorski 1984; Breedlove 1986; Goy and McEwen 1980; Harris and Levine 1965; Rhees et al. 1990). Thus, treatment of female neonates with sex steroids during the first few postnatal days alters the number of neurons residing in certain nuclei, as well as the morphology, synaptology, and neurotransmitter expression of individual neurons (Arai et al. 1986; Arnold and Jordan 1988; De Vries 1990; Gorski 1985; Raisman and Field 1973; Simerly 1989, 1991).

Introduction

Gonadal steroid hormone receptors are ligand-activated transcription factors that are part of a complex superfamily of such factors (Evans 1988). These receptors alter the transcription of genes containing specific promoter or enhancer sequences. In this way, estrogen, acting through the estrogen receptor (ER), alters the transcription of genes in the cells where the receptors are found.

Neurons that contain gonadal steroid hormone receptors are a key to the mechanisms through which these hormones govern the behavioral and neuroendocrine processes underlying reproduction (Morrell et al. 1975; Morrell and Pfaff 1983). A complex and only partly understood cascade of events occurs subsequent to the genomic regulation initiated by these ligand-activated transcription factors (Yamamoto 1985). The presence of gonadal steroid hormone receptors in neurons has been documented by means of steroid hormone autoradiography, biochemical assays for binding, and immunocytochemistry (Blaustein and Olster 1989; DonCarlos et al. 1991; Giordano et al. 1991; Morrell et al. 1992). Now the tools of molecular biology provide a means of investigating the mRNA from which gonadal steroid hormone receptors are translated.

The differential sensitivity of brain regions to steroid hormones is based on the combination of the regional location of neurons containing these receptors, the number of neurons containing the receptors per brain region, and the number of receptors per neuron. The degree of sensitivity to steroid hormones is not a static property of the brain as there is increasing evidence that the endocrine and behavioral status of the adult mammal can govern the sensitivity of brain regions to steroid hormones by regulating either the number of neurons expressing the receptors or the amount of receptor per neuron (Hnatczuk et al. 1994; Koch and Ehret 1989; Pearson et al. 1993; Simerly and Young 1991).

Many books are subject to the fundamental questions “Why this topic?” and “Why now?” Scientific texts are perhaps most susceptible because they often present similar topics. As a partial answer to these questions, we paraphrase P. B. Medawar in his Advise to a Young Scientist: We have tried to prepare the kind of book that we ourselves would like to read and have as a reference.

In recent years, the field of reproductive neuroendocrinology has experienced a renaissance brought about by the application of cellular and molecular biological techniques. We have made significant progress in understanding the mechanisms that underlie central nervous system control of reproductive behavior. This progress has been well documented at various meetings and in individual papers. We felt it was necessary, therefore, to offer a collection of essays by some of those who have contributed to this renaissance. We hasten to add that the chapters in this volume do not necessarily reflect all of the vital issues of behavioral neuroendocrinology. Rather, they represent brief reviews by and current data from a number of productive scientists in this field.

Because of a limitation of space, several important topics are not discussed or are only briefly presented in this volume. These include the spinal nucleus of the bulbocavernosus system, cell membrane steroid receptors, interactions of steroids with γ-aminobutyric acid receptors, the songbird neural circuitry, as well as the insect and amphibian models of reproduction and metamorphosis. Each of these models has proved to be extremely useful for studying the effects of sex steroid hormones on the nervous system.

Introduction

For neuroscientists, the study of sex differences in the brain promises at least two benefits. Investigations of their development can elucidate the processes that form brain structure during ontogeny that generates specific functions and behaviors, while investigations of the functional significance of these sex differences can reveal how brain morphology and function are related. Except for the fact that sex-related differences in the number of spinal motoneurons have been linked to sex-related differences in the number of specific muscle cells (Kelley 1988; Breedlove 1992), these benefits have been difficult to achieve, however. The complexity of the neuroanatomical connections to and from the brain regions where these differences are found and technical difficulties in manipulating specific sexually dimorphic elements in these areas have delayed the desired result.

This complexity, however, can be exploited. Given that all brain areas contain heterogeneous populations of cells and inputs, focusing on the neurotransmitter content of cells and inputs could reveal whether sexual differentiation selectively affects particular cell populations. This, in turn, could facilitate our understanding of the cellular processes underlying differentiation. Focusing on the neurotransmitter content may also help to reveal the anatomical connections of sexually dimorphic areas, and therefore to assess the impact of a particular dimorphism on other brain areas. Finally, knowing the neurotransmitter systems involved would allow specific manipulation of sexually dimorphic elements by applying specific agonists and antagonists (De Vries 1990).

Steroid hormones act on the brain to influence its organization during development and its activity in adulthood, thereby regulating behavior and physiology. Achieving these effects on the brain is often the culmination of a complex set of events within the endocrine system. During development, the sequence begins with the differentiation of steroid-secreting organs and their expression of steroidsynthetic enzymes. In adulthood, it continues with the regulation of the activities of one or more of these enzymes by pituitary trophic factors. After secretion, but before the steroid reaches targets within specific brain cells, the hormone is subject to a variety of regulatory influences. These can include steps to-inactivate the molecule by peripheral catabolism and excretion. The presence of carrier proteins in blood can limit the availability of free steroid to enter tissues. Having reached a target organ, the steroid may encounter additional enzymes that catalyze changes in its structure, rendering the molecule inactive. Alternatively, the steroid may be converted to a molecule with increased biological activity or one that functions along an alternative steroid-activating pathway. When these transformations are complete, the steroid is available to influence cellular function by interacting with intracellular protein receptors. Once bound to ligand, the steroid receptor can bind to specific DNA hormone response elements to influence the transcription of specific genes. The active steroid may also influence cell function without changing gene expression by interacting directly with cell membranes or with other cellular processes.

Role of the medial preoptic area in the hormonal control of male sexual behavior

Mating behaviors of males provide excellent examples of the neurobiological effects of sex steroid hormones. In mammals (Larsson 1979; Michael and Bonsall 1979; Sachs and Meisel 1988), birds (Balthazart 1983; Silver et al. 1979), and other vertebrates (Crews 1979; Crews and Silver 1985; Kelley and Pfaff 1978), testosterone (T) promotes the sexual activity of adult males. Gonadally intact males are more likely to mount receptive females, and to copulate to ejaculation, than are castrated males, unless the castrates are given T. Although these stimulatory effects of T result largely from its action on the brain (Kelley and Pfaff 1978; Larsson 1979; Sachs and Meisel 1988), T also acts on the penis and spinal neurons to affect copulatory performance (Breedlove 1984; Hart 1978; Hart and Leedy 1985; Sachs 1983).

Within the brain, one of the most important areas mediating the effects of T on male sex behavior is the medial preoptic area (MPOA) or the MPOA–anterior hypothalamus (AH) continuum. The MPOA–AH contains many cells that accumulate T or its metabolites, estradiol (E) and dihydrotestosterone (DHT) (Kelley and Pfaff 1978; Luine and McEwen 1985; Michael and Bonsall 1990). However, the conclusion that the MPOA–AH mediates many of the effects of T on male sexual behavior is based on the behavioral changes produced by manipulations of this area (Sachs and Meisel, 1988). Implanting T or E into the MPOA–AH restores mounting in castrated males, and lesioning the MPOA–AH eliminates sexual behavior in males that are exposed to circulating T.

Acetylcholine was the first endogenous chemical to be identified as a neurotransmitter. In addition to its vital role in physiology, acetylcholine has been implicated in the regulation of mammalian behaviors that range from reflexive (Potter et al. 1990) to regulatory (Hagan et al. 1987) to cognitive (Levin et al. 1990). The control of these heterogeneous behaviors appears to be possible because of diffuse cholinergic circuits distributed throughout the mammalian brain (Mesulam et al. 1983). The organization of these systems, particularly in the forebrain and midbrain, places cholinergic neurons in regions involved in sensory, motor, and motivational processes.

Our work during the past decade has indicated that cholinergic systems also play an important role in the regulation of certain behaviors exhibited by mammalian females during mating. It is well known that the sexual behaviors of female rodents are controlled closely by steroid hormones, primarily estrogen and progesterone secreted by the ovaries. However, the sequence of neural events initiated by these hormones to cause complex behavioral responses has not been described fully. The capacity of cholinergic mechanisms to affect rodent sexual behavior suggests a key interface between endocrine activity and cholinergic function. Our primary hypothesis states that ovarian steroids regulate brain function, and consequently behavior, by altering the activity of cholinergic systems within neural target structures. According to current theories of hormone action, steroids could access nuclear genomes (O'Malley and Means 1974) and surface membranes (Schumacher 1990) to alter the nature and number of various proteins associated with cholinergic neurotransmission.