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There is a major need to overcome therapeutic resistance and metastasis that eventually arises in many breast cancer patients. Therapy resistant and metastatic tumors are increasingly recognized to possess intra-tumoral heterogeneity (ITH), a diversity of cells within an individual tumor. First hypothesized in the 1970s, the possibility that this complex ITH may endow tumors with adaptability and evolvability to metastasize and evade therapies is now supported by multiple lines of evidence. Our understanding of ITH has been driven by recent methodological advances including next-generation sequencing, computational modeling, lineage tracing, single-cell technologies, and multiplexed in situ approaches. These have been applied across a range of specimens, including patient tumor biopsies, liquid biopsies, cultured cell lines, and mouse models. In this review, we discuss these approaches and how they have deepened our understanding of the mechanistic origins of ITH amongst tumor cells, including stem cell-like differentiation hierarchies and Darwinian evolution, and the functional role for ITH in breast cancer progression. While ITH presents a challenge for combating tumor evolution, in-depth analyses of ITH in clinical biopsies and laboratory models hold promise to elucidate therapeutic strategies that should ultimately improve outcomes for breast cancer patients.

In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (NTAIL) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of NTAIL even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

Several fictitious scenarios provide us with questions about the nature of artificial and natural feelings. It turns out that, traditionally, three features are relevant for the attribution of an emotion to humans: the functional role it typically has; the phenomenal quality that typically accompanies it; and the neurophysiological basis that brings about the phenomenal state. On the basis of these features I discuss several cases: artificially generated feelings, feelings in artificial systems, and unfelt emotional processes in psychopathology.

There is incontrovertible evidence that the MHC region is associated with type-specific odours in a number of species. Existing experimental paradigms have demonstrated that animals can discriminate between classes of MHC-associated odour with great acuity. Furthermore, experiments on mate choice and kin selection provide convincing evidence of a functional role for these odours. At the moment, evidence for genuine individual recognition or discrimination, meaning the “learned discrimination among conspecific individuals” (Halpin, 1986; p. 44), is lacking. This is partly because the four main experimental paradigms have not been used explicitly to address the question of individual recognition, but rather to test whether broader subgroups of MHC-associated odours exist and are distinguishable. These types of experiment can certainly be adapted to test individual recognition. For example Gheusi et al., (1997) found evidence for individual discrimination by rats using operant training, although this study did not examine MHC-associated odours specifically. The experimental paradigms described here have been vital in narrowing down the search for potential sources of individual odours, and testing odour discrimination abilities. Ultimately however, they can only allow an assessment of olfactory acuity, rather than whether this acuity is put to any use. In order to demonstrate that MHC-associated odours have an adaptive role in individual recognition, functional tests in a realistic behavioural context are required. Such functional tests exist (e.g. see Rich and Hurst, 1999; Hurst et al., 2001; Lai and Johnston, 2002) and now need to be applied to the unresolved issue of MHC-associated odours and individual recognition.

The optic nerve is the structure that transmits information from the retina to the brain. It is composed of ganglion cell axons, astroglial cells, oligodendrocytes, microglia, blood vessels and connective tissue. The astroglia cells perform important functions, including formation of astroglial limiting membranes and organisation of the ganglion cell axons of the retina into bundles throughout their course along the nerve. There are two morphological types of astrocytes, thick and thin, whose morphologies change according to the region of the nerve that they occupy. On the surface nerve fibre layer (SFNL) the thin-bodied astrocytes issue long processes which follow the course of the axons and make contact with the capillaries derived from the central retinal artery: in the anterior prelaminar region (PR) the thin-bodied astrocytes assume a star shape and their processes are arranged in a basket formation. In the posterior PR the astrocyte are thick bodied and make up glial tubes inside which the nerve fibres travel towards the laminar region (LR). In the LR, the thick bodied astrocytes cover the inner surface of the pores of the lamina cribosa; and finally in the retrolaminar region (RR) they separate the nerve tissue from the connective tissue. The glial limiting membranes are composed of thick-bodied astrocytes.

Numerous studies attest to the fact that low frequency oscillations are present in measurements of blood flow, volume and diameter changes in the microvasculature. The presence of these oscillations has been known and studied for nearly a century (1, 2). While several low frequency oscillations have been detected, the most frequently reported and studied has a frequency of U0.1 Hz, or 6 cycles/minute, i.e., a period of about 10 seconds. The commonly accepted explanation of the U0.1Hz oscillations is by mechanisms either myogenic (3, 4) and/or neurogenic (5, 6) in origin acting on resistance vessels (arteries and arterioles) to change their diameter with the effect that the modulation of flow rate produces oscillatory changes in saturation and volume. The mechanisms and dynamics underlying these changes in flow rate are complex, and as yet not well understood, and it is uncertain if they have a functional role.

Techniques of in vitro whole-cell recording and compartmental modeling were combined to investigate dendritic structure and calcium currents in individual thalamocortical neurons. Voltage-clamp recordings of I T obtained in intact and dissociated ventrobasal neurons were used to constrain I T conductances and passive parameters incorporated in morphorealistic models. High dendritic I T densities were found necessary to establish congruent model behavior. Several methodologies based on axial resistance conservation were developed to algorithmically reduce thalamocortical morphology into a behaviorally congruent low-order compartmental model. This type of simplified model is suitable for investigating the functional role played by distal T- current localization at the network level in sleep oscillations and epilepsy.

Computer simulation with simplified but fairly detailed model neurons can be powerful in evaluating to what extent known cellular and synaptic properties can account for the behavior seen at the system level and also allow analysis of the relative functional role of different components and mechanisms which might be difficult to address only experimentally. We have evaluated the role of low voltage-activated (LVA) calcium channels both on the single cell and network level in the lamprey locomotor circuitry. A previous computer simulation model has been extended with LVA calcium channels using the m 3h form, following a Hodgkin—Huxley paradigm. Experimental data from mainly lamprey neurons [9] was used to provide parameter values of the single cell model.

The development of in vitro preparations of the spinal cord has catalysed our understanding of locomotor network organisation in simple vertebrates (Grillner & Matsushima, 1991; Roberts & Tunstall, 1990). This is because such preparations are stable enough to allow long term single or dual intracellular penetrations of spinal neurones to establish their firing behaviour, synaptic drive and network connections. Although in vitro spinal preparations of higher vertebrates have been available for many years (Otsuka & Konishi, 1974) it is only relatively recently that they have become widely used for studies of locomotion and respiration (Landmesser & O’Donovan, 1984; Smith & Feldman 1987; Kudo & Yamada, 1987). Application of the classical electrophysiological methods will be more challenging in the these preparations because of their greater complexity and large cell complement. Furthermore, single cell methods are a laborious way of documenting the activity of neuronal populations and cannot readily provide information about the complex spatiotemporal patterns of network activation. Another limitation of this approach is that it is purely descriptive. It provides no information about the causal role of particular cell classes in the genesis of the behaviour. In invertebrate systems the functional role of a neurone in a network is often inferred after lesioning the cell or hyperpolarising its membrane potential during network behaviour. While such a strategy has limitations it can be successfully applied to identify the role of certain classes of cell in rhythm generation. One good example of this approach is the lesioning of efferent neurones in the mollusc Clione limacina to show that they are not required for rhythmogenesis (Arshavsky, Orlovsky & Panchin, 1985).

A variety of observations call attention to the potential significance of CNP in CNS myelination1–6. Although this protein is not unique to oligodendrocytes, these cells are the only ones to express it in the CNS. CNP is the earliest of all known myelination-related proteins to appear developmentally in oligodendrocytes; it accumulates in the cytoplasm-containing compartments of the myelin sheath, and is absent from compact lamellae4,7. Despite several interesting primary structural domains that are shared by other proteins, including several that are involved in signal transduction2,3,5 and an isoprenylated domain6, CNP is not assignable to any family of known proteins by virtue of overall sequence homology. This and the catalytic potential for hydrolysis of 2′-3′-cyclic nucleotides to yield 2′-nucleotides (a reaction of no known physiological significance for events in the cytosol) have left the problem of a functional role unresolved.

In recent years there has been increasing interest in the study of the mode of action of botulinum neurotoxin (BoNT) and tetanus toxin (TeTx) at the cellular level (for recent reviews see Simpson, 1986, 1989; Habermann and Dreyer, 1986; Niemann, 1991; Poulain and Molgo, 1992; Wellhoner, 1992, Dolly, 1992, and this volume). This is mainly due to the unique ability of these toxins to effectively block neurotransmitter release in all types of nerve terminals once they gain access inside the nerve endings; BoNTs and TeTx are, thus, useful research tools to study transmitter release mechanisms and tools in medicine. Deciphering their intracellular modes of action still remains a challenge for future research; however, during the last decade continuous progress has been made in the identification of the functional domains of BoNTs and TeTx implicated in the multiple facets of the intoxication. Using neuronal preparations from Aplysra, an identification of the functional role of different protein domains of BoNTs and TeTx has been made which contrasts somewhat with those proposed for vertebrates. Thus the aim of the present paper is to review data in Aplysra and, also, to stress the similarities and differences into observations made in the various models.

Different functions have been ascribed to the paraganglionic SIF cells located in sympathetic ganglia: they were considered as interneurons, neuroendocrine and/or chemoreceptive cells (Case and Matthews, 1985). In many was, they resemble glomus cells of peripheral chemoreceptors (Kondo, 1977). However, elucidation of their functional role is still difficult because SIF cells are few in number comparatively to the postganglionic neurones, because their incidence varies greatly according to the species and to the ganglia and because they contain numerous putative neurotransmitters.

Even though normally present in relatively small amounts, myocardial collagen strongly influences ventricular diastolic function. Removal of less than half of the normal amount results in a dilated ventricle with increased compliance. In contrast, an abnormal increase in collagen concentration results in a stiffer myocardium and ventricular diastolic dysfunction.

In this chapter, we will review our current work in case-based approaches to planning. Our research examines the organization and structure of episodic memory as determined by its functional role in guiding reasoning. The theoretical thrust is based upon the intuition that a large part of the reasoning process is guided by the contents and organization of events in memory. The major goal of this work is the development of functional explanations of the representational organization and conceptual vocabularies that support reasoning tasks. Our current work can be characterized in terms of three major tasks: Uncovering vocabularies for describing causal similarities between episodes in memory. Examining the use of features in the access and retrieval of cases from memory. Understanding the role of memory organization in the support of opportunistic planning and problem solving.

New techniques to study RNA have lead to a rapid accumulation of data indicating that ribosomal RNA (rRNA) is part of every functional site on the ribosome. The emphasis is now on the functional role played by rRNA (Reviewed by Noller, 1991), rather than by ribosomal proteins.

The study of the cerebellum has a long and fascinating history, spanning many centuries. As Dow describes in his detailed historical review of cerebellar investigation [1], the Greek physician Herophilus (335–200 BC), known as the “father of anatomy,” is generally credited for recognizing the human cerebellum as a distinct brain division. About two millienna later, Sir Thomas Willis (1621–1675) made comparative anatomical observations drawing attention to the characteristic morphologic appearance of the cerebellum in vertebrates. It seems that these observations stimulated interest in understanding the functional role of the cerebellum, which, until then, had remained obscure. It was, however, Luigi Rolando (1773–1831) who began a new era in cerebellar research by developing ablation experiments in an effort to understand the function of this brain area. Based on this work, he correctly suggested that the cerebellum is involved in motor control. Such ablation techniques, along with the subsequently developed stimulation methods, have served as basic experimental tools for understanding the cerebellar physiology for almost two centuries.

The issue whether acetaldehyde plays a functional role in the actions of alcohol remains a controversial area following more than two decades of investigation. The publication of several extensive reviews (Lindros, 1978; Amir et al., 1980; von Wartburg, 1980; Brien and Loomis, 1983, Amit and Smith, 1989) have left little doubt that the first metabolic product of alcohol oxidation is an important contributor to some of the consequences of exposure to ethanol. Unfortunately, despite the massive literature that accumulated during this period, there is, as yet, little consensus concerning which actions of alcohol (if any) are a function of the formation of acetaldehyde.

The snRNAs have been described in all eukaryotic cells from mushrooms and protozoa to higher plants and mammals (Busch et al., 1982). The involvement of snRNA in splicing and its role as autocatalyst has been discovered (Maniatis and Reed, 1987). However, at the present time the functional role of these macromolecules has not been investigated in detail.

There is now an increasing body of evidence to support the idea that Cns and Pns gangliosides may play an important functional role in various nervous tissues although their precise role has not yet been elucidated. There is also good biochemical evidence that gangliosides are highly concentrated in the nerve terminals, most of them associated with the nerve terminal plasma membrane (Burton, 1976; De Robertis et al. 1976; Morgan et al. 1976), nevertheless any clear relationship between the subcellular distribution of gangliosides within the different nerve terminal membranes and the normal chain of events involved in transmitter release and the overall synaptic economy has not been yet established. In spite of these uncertainties we thought that it might be useful to test the effects of gangliosides during the process of nerve regeneration and reinnervation of target tissues.

The brain ganglioside pattern of taxonomically close and distant related fishes living at different temperatures were compared with the mammalian pattern. Furthermore the goldfish brain pattern was investigated after adaption (acclimatization, acclimation)to different temperatures. The results demonstrate correlations between body temperature and brain gangliosides: the lower the body temperature of animals, the higher the relative proportion of multi-sialo-gangliosides. The results are discussed with respect to the possible functional role of Ca++ ganglioside-complexes for the process of synaptic transmission.

The superior colliculus is a phylogenetically old cortex, but determination and measurement of its function in primates has proved to be a particularly difficult and challenging task. It has been known for over a century that stimulation of the colliculus produces eye movements (Adamuk, 1870), but no experimental design has yielded an adequate answer to the question of the exact functional role of the colliculus.

We have chosen to study the chloroplast ATP synthase (CF0CF1) as a system to find out whether interactions with specific glycolipids have a functional role in the catalytic activity of this enzyme. The reasons for selecting this enzyme are: (a) CF0CF1 can be easily and reversibly delipidated, whereby it looses most of it catalytic activity. The activity is regained upon reconstitution with phospholipids. (b) CF0CF1 is specificaly activated by octylglucoside, a glycodetergent, suggesting that octylglucoside mimics specific interactions between CF0CF1 and glycolipids in thylakoid membranes (1). In this paper we summarize the results of several approaches aimed to identify interactions between CF0CF1 and chloroplast glycolipids.

Inborn errors in ganglioside metabolism produce large changes in cellular functions, but as yet the biochemical role of gangliosides has not been established. Several models have been used to elucidate their role and some encouraging data have been reported. Thus, theoretical as well as biochemical studies have implicated gangliosides in the functioning of specialized plasma membranes (1). Nevertheless, the complexity of the nervous tissue restricts the understanding of their precise functional role.

Although the central mechanisms mediating the voluntary consumption of ethanol have not as yet been determined, a number of hypotheses have been proposed based on the available evidence. The biogenic amines that have been implicated in the mediation of reward (e.g. Fibiger, 1978; German and Bowden, 1974; Stein 1968; Zigmond and Strieker, 1972) have also been shown to play a functional role in the pharmacological actions of ethanol. This notion has been supported by the numerous demonstrations that ethanol administration produces alterations in the metabolism of the central biogenic amines (e.g. Bonnycastle, Bonnycastle and Anderson, 1962; Carlsson, Magnusson, Svensson and Waldeck, 1973; Corrodi, Fuxe and Hokfelt, 1966; Hunt and Majchrowicz, 1974). While the effects of serotonin (5-HT) manipulations on ethanol consumption have been equivocal (e.g. Hill, 1974; Myers, 1968; Myers and Melchior, 1975a, b), there has been greater consistency in the reports that catecholamines (CA), and norepinephrine (NE) in particular, may mediate the reinforcing properties of ethanol(e.g. Amit, Brown, Levitan and Ogren, 1977; Amit and Stern, 1971; Brown and Amit, 1977; Davis, Smith and Werner, 1977; Myers and Melchior, 1975a).

The eosinophil is a polymorphonuclear leukocyte which is characterized by the high affinity of its cytoplasmic granules for acid analine dyes, most commonly eosin. Investigations and interest have been focused on eosinophils for approximately 100 years. Various aspects of this cell have been the topics of a recent book and several current reviews (Beeson and Bass, 1977; Lukens, 1972; Speirs et al., 1974; Zucker-Franklin, 1974; Ottesen, 1976; Butterworth, 1977; Goetzl and Austen, 1977; Kay, 1977; Gupta, 1977, and personal communication; Phillips and Colley, 1978). It would seem that their phylogenetic credentials, tracing back to all but the most primitive vertebrates, and their unique lineage, life cycle, tissue distribution, morphology, and biochemical activities might have earned the eosinophils a distinct position in the biomedical realm. However, most often, the eosinophil is still known through its associations with a variety of other situations, such as infections with certain tissue-dwelling helminths, atopic disorders, and some immune-complex-related disorders. The occurrence of eosinophils in a given environment thus remains relegated to the position of an epiphenomenon. The explanation of why the eosinophil continues to earn only this “associated with” status seems clearly to be based on an inability to assign a functional role to this cell. Most of the current information available continues to deal with the governance of eosinophils by other systems. There are, however, several different eosinophil-related activities which are now being examined as possible functional roles for eosinophils. This chapter will attempt to describe the eosinophil, discuss its various associations with immune responses, and examine the nature of its activities as an integral component of some of these systems.

The corticostriatal pathway is a massive projection system linking virtually the entire neocortex with the neostriatum. Although it is widely recognized as a vital relay between cognitive centers and the extrapyramidal motor system, the exact nature of the anatomical relationship between these major centers has remained a puzzle to neurologists and neuroscientists alike. The functional role of the neostriatum has been equally clouded. The behavioral consequences of lesions in this structure are astonishingly diverse and seem not to be consistent from one study to another or from one species to another, including man (Denny-Brown, 1962; Divac and Oberg, 1979; DeLong and Georgopoulus, 1981).

Within the coelenterates the ability to emit light is widely distributed; most of the major coelenterate taxa contain both luminescent and non-luminescent species (Harvey, 1952; Morin, 1974. Production of light within the luminescent species is biochemically, structurally, and physiologically complex (Harvey, 1952; Nicol, 1960; Herring, 1972; Buck, 1973; Morin, 1974; Morin and Reynolds, 1974; Cormier et al., 1975; Anderson and Case, 1975). The complicated mechanisms responsible for the well-controlled light emission suggest that the light serves some functional role in the life of these organisms. In this paper I discuss the characteristics of the luminescent signal in four pennatulaceans (sea pens) and then consider the ways that the light is potentially employed by these pennatulaceans, and possibly by all luminescent benthic cnidarians.

Taurine is an ubiquitous constituent of animal tissues (25); its highest levels are found in excitable organs like brain, heart and secretory glands, where it may reach concentrations as high as 20–100 mM (8,25,27). In spite of its wide distribution and of recent interest in studies on taurine, the elucidation of its functional role has been particularly difficult. Taurine is not associated to proteins and except for the formation of taurocholic acid it does not participate in metabolic reactions. Therefore, it could be thought that the presence of taurine in a tissue or organ should be related only to the specific function subserved by the amino acid. In this communication we will consider some possible roles of taurine in nervous tissue.

The role of the substantia nigra (SN) in the control of motor activity has mainly been analyzed through clinical data on Parkinson’s disease in human subjects (Marsden, 1982). This disease has been known for a long time to involve progressive degeneration of the pigmented neurons in the SN (Tretiakoff, 1919; Hassler, 1938). Identification of the nigrostriatal dopaminergic projection (Anden et al., 1964) from these pigmented neurons gave rise to studies in which striatal dopamine (DA) deficit was proved to be responsible for the onset of the symptoms of Parkinsonism, particularly akinesia and rigidity (Hornyckiewicz, 1966; Bernheimer et al., 1973). Besides these clinical observations on human patients, a body of experimental work has been published on animals (see Schultz, 1982) discussing the functional role of the SN.

Despite ample evidence of the role of T lymphocytes in rejecting tumor cells as well as allografts,(1) there are large gaps in our understanding of the effector mechanisms responsible for graft rejection. It is clearly important for both scientific and clinical reasons to define the effector mechanisms that take place within a rejecting tumor graft. The identification of an effector mechanism within a tumor graft does not necessarily imply a functional role for the mechanism in tumor destruction in vivo. Therefore, in considering the relevance of a particular mechanism, we must know whether the effector mechanism detected is subsidiary, necessary, or sufficient for tumor rejection in vivo.

This Workshop has examined the functional role of various components of the arterial wall in relation to atherogenesis. My task is now to summarise the new information which has been presented, to contrast this with existing knowledge and to consider points which are still the subject of controversy.

Amygdalar neurons respond to complex visual stimuli and activity changes at the sight of food (Ono et al., 1983; Sanghera et al., 1979). The amygdala (AM) is among the richest of the brain areas in opioid receptors and endogenous ligands, but the functional role of its opioid system in feeding behavior is not yet understood.

Adenosine and related compounds can probably play a transmitter or cotransmitter role at least in some tissues (e.g., Burnstock, 1985). However, this seems to be rare and the major functional role of adenosine not only in the periphery but also in the nervous system appears to be that of a modulator. Adenosine is released not only from nerve terminals but also from cell bodies and from glial cells or endothelial cells lining the cerebral blood vessels. Besides its role in blood-flow regulation, adenosine clearly plays a role in modulation of nervous activity, pre- and postjunctionally.

Nuclear-encoded proteins which are destined for import into mitochondria face at least two major problems during the course of transport from their site of synthesis in the cytoplasm to their site of function in the mitochondria. First, they must be sorted specifically to the mitochondrial outer membrane and must avoid being targeted to any of the other cytosol-exposed membranes. Second, they must somehow overcome the hydrophobic barrier of the mitochondrial membranes and pass one or both of the organelle’s lipid bilayers. A molecular understanding of the mechanism of these processes is the ultimate goal of current research on this topic. This paper will present ideas about how the presequence portion of a mitochondrial precursor protein may function both in the sorting and translocation stages of import.

The exact localization of a compound in normal tissue and its redistribution in neurological diseases and disease models can give important clues as to the functional role of the compound in question. In the case of taurine (2-aminoethanesulfonic acid), so far only biochemical methods have been available for its localization. Such methods will necessarily have a limited anatomical resolution and may easily fail to detect important pathological alterations in the cellular and subcellular distribution of taurine. A much better anatomical resolution is provided by the immunocytochemical technique, which has recently been adapted to amino acids (24). Antisera against conjugated amino acids have been employed to map the light- and electronmicroscopic localization of GABA, glutamate, glutamine, asparatate, and glycine in normal nerve tissue (1,2,6,9,10,17,18,19,22,24), and have also been used to study the redistribution of transmitter amino acids in experimental models of epilepsy (14).

Generally, the monolayers are considered as halves of bilayers, and their physical properties can be compared to those of the biological membranes. Moreover, these systems fit to mimic biomembranes, providing considerable insight into the structural and functional role of their constituents, such as lecithins.

The reactions which constitute the pathway for tryptophan biosynthesis exhibit an unusual degree of organizational diversity throughout the biological world. The component reactions of this pathway, including those involved in general aromatic biosynthesis, are organized in different patterns of multifunctional complexes; and this diversity is reflected in specific patterns of gene-enzyme relationships. Some of the first reported examples of multifunctional proteins and channelling of intermediates between active sites in multifunctional proteins were uncovered by the extensive biochemical and genetic studies of this pathway. To illustrate the organization of active sites in multifunctional protein complexes, I will review several well-defined examples from this pathway. In this review my emphasis will be on the current status of our understanding of the structure of multifunctional enzymes and the possible functional role of enzyme organization within this pathway.

The premise that complex carbohydrate structures have a functional role at the cellular level must be immediately followed by the admission that not a single mammalian cellular complex carbohydrate structure has yet been clearly associated with a physiological cellular function. On the other hand, there is now abundant reason to believe that such structure-function relationships will soon be demonstrated. It also seems clear that the rate of progress in this area is directly related to the rate of progress with the structural half of the relationship. At the moment, there are two general sources of structural information. First, detailed structural information on a fairly broad range of complex carbohydrates that are extracellular products of cells is now available. This information can be used to establish a conceptual framework of the kinds of structure to look for at the cellular or subcellular level. Second, there now exists detailed structural information on one or two cellular complex carbohydrates of unknown function (blood group substances).

Motor responses in which a given motor cortex cell may play a functional role can be elicited by operantly reinforcing bursts of cell activity and observing the correlated behavioural responses. Under isometric conditions, operant bursts were often repeatedly correlated with EMG bursts in specific contralateral arm muscles. These EMG bursts broadly coincided with the operant unit bursts, but their onset and peak usually followed the onset and peak of the precentral unit burst. One may refer to the set of muscles co-activated with operant bursts of a motor cortex cell as the cell’s “motor field”. Under isometric conditions the motor field of a given cell generally remained stable over many bursts, not only with respect to the set of co-activated muscles, but also with respect to the relative intensity of their activation. Different units in the same cortical region could have quite different motor fields. Many of the unit-muscle correlations observed when the unit was reinforced were replicated during other reinforced response patterns.