Long-Term Potentiation (LTP) is a kind of synaptic plasticity that many contemporary neuroscientists believe is a component in mechanisms of memory. This essay describes the discovery of LTP and the development of the LTP research program. The story begins in the 1950's with the discovery of synaptic plasticity in the hippocampus (a medial temporal lobe structure now associated with memory), and it ends in 1973 with the publication of three papers sketching the future course of the LTP research program. The (...) making of LTP was a protracted affair. Hippocampal synaptic plasticity was initially encountered as an experimental tool, then reported as a curiosity, and finally included in the ontic store of the neurosciences. Early researchers were not investigating the hippocampus in search of a memory mechanism; rather, they saw the hippocampus as a useful experimental model or as a structure implicated in the etiology of epilepsy. The link between hippocampal synaptic plasticity and learning or memory was a separate conceptual achievement. That link was formulated in at least three different ways at different times: reductively (claiming that plasticity is identical to learning), analogically (claiming that plasticity is an example or model of learning), and mechanistically (claiming that plasticity is a component in learning or memory mechanisms). The hypothesized link with learning or memory, coupled with developments in experimental techniques and preparations, shaped how researchers understood LTP itself. By 1973, the mechanistic formulation of the link between LTP and memory provided an abstract framework around which findings from multiple perspectives could be integrated into a multifield research program. (shrink)

To explain their role in discovery and contrast them with theory-driven research, philosophers of science have characterized exploratory experiments in terms of what they lack: namely, that they lack direction from what have been called “local theories” of the target system or object under investigation. I argue that this is incorrect: it’s not whether or not there is direction from a local theory that matters, but instead how such a theory is used to direct an experiment that matters. Appealing to (...) contemporary exploratory experiments that involve the use of experimental techniques—specifically, examples where scientists explore the interaction of neural activity and human behavior by magnetically stimulating brains—I argue that local theories of a target system can inform auxiliary hypotheses in exploratory experiments, which direct these experiments. These examples illustrate how local theories can direct the exploration of target systems where researchers do not aim to evaluate these theories. (shrink)

I introduce two new tools in experimental neurobiology, optogenetics and DREADDs. These tools permit unprecedented control over activity in specific neurons in behaving animals. In addition to their inherent scientific interest, these tools make an important contribution to philosophy of science. They illustrate the very premises of Ian Hacking’s “microscope” argument for the relative independence of experiment from theory. This new example is important for generalizing Hacking’s argument because the background sciences and the fields of engineering producing these tools differ (...) significantly. (shrink)

Many studies of the unification of science focus on the theories of different disciplines. The model for integration is the theory reduction model. This paper argues that the embodiment of theories in scientists, and the institutions in which scientists work and the instruments they employ, are critical to the sort of integration that actually occurs in science. This paper examines the integration of scientific endeavors that emerged in cell biology in the period after World War II when the development of (...) cell fractionation and electron microscopy made serious investigations of cell organelles possible. One surprising feature of such integration is that it generated further disintegration as the new institutions of cell biology separated the practitioners of the new discipline from other, closely related biological disciplines. (shrink)

Descriptive accounts of the nature of explanation in neuroscience and the global goals of such explanation have recently proliferated in the philosophy of neuroscience and with them new understandings of the experimental practices of neuroscientists have emerged. In this paper, I consider two models of such practices; one that takes them to be reductive; another that takes them to be integrative. I investigate those areas of the neuroscience of learning and memory from which the examples used to substantiate these models (...) are culled, and argue that the multiplicity of experimental protocols used in these research areas presents specific challenges for both models. In my view, these challenges have been overlooked largely because philosophers have hitherto failed to pay sufficient attention to fundamental features of experimental practice. I demonstrate that when we do pay attention to such features, evidence for reduction and integrative unity in neuroscience is simply not borne out. I end by suggesting some new directions for the philosophy of neuroscience that pertain to taking a closer look at the nature of neuroscientific experiments. (shrink)

Starting with some illustrative examples, I develop a systematic account of a specific type of experimentation--an experimentation which is not, as in the "standard view", driven by specific theories. It is typically practiced in periods in which no theory or--even more fundamentally--no conceptual framework is readily available. I call it exploratory experimentation and I explicate its systematic guidelines. From the historical examples I argue furthermore that exploratory experimentation may have an immense, but hitherto widely neglected, epistemic significance.

Optogenetics makes possible the control of neural activity with light. In this article, I explore how the development of this experimental tool has brought about methodological and theoretical advances in the neurobiological study of memory. I begin with Semon’s distinction between the engram and the ecphory, explaining how these concepts present a methodological challenge to investigating memory. Optogenetics provides a way to intervene into the engram without the ecphory that, in turn, opens up new means for testing theories of memory (...) error. I focus on a series of experiments where optogenetics is used to study false memory and forgetting. (shrink)

Neuroimaging studies of the resting state continue to gather philosophical and scientific attention. Most discussions assume an identification between resting-state activity and activity in the so-called default mode network. I argue we should resist this identification, structuring my discussion around a dilemma first posed by Morcom and Fletcher. I offer an alternative view of rest as a state dominated by long-term processes and show how interaction effects might thereby let rest shed light on short-term changes in activation.

This paper analyzes what it means for philosophy of science to be normative. It argues that normativity is a multifaceted phenomenon rather than a general feature that a philosophical theory either has or lacks. It analyzes the normativity of philosophy of science by articulating three ways in which a philosophical theory can be normative. Methodological normativity arises from normative assumptions that philosophers make when they select, interpret, evaluate, and mutually adjust relevant empirical information, on which they base their philosophical theories. (...) Object normativity emerges from the fact that the object of philosophical theorizing can itself be normative, such as when philosophers discuss epistemic norms in science. Metanormativity arises from the kind of claims that a philosophical theory contains, such as normative claims about science as it should be. Distinguishing these three kinds of normativity gives rise to a nuanced and illuminating view of how philosophy of science can be normative. (shrink)

In contemporary human brain mapping, it is commonly assumed that the “mind is what the brain does”. Based on that assumption, task-based imaging studies of the last three decades measured differences in brain activity that are thought to reflect the exercise of human mental capacities (e.g., perception, attention, memory). With the advancement of resting state studies, tractography and graph theory in the last decade, however, it became possible to study human brain connectivity without relying on cognitive tasks or constructs. It (...) therefore is currently an open question whether the assumption that “the mind is what the brain does” is an indispensable working hypothesis in human brain mapping. This paper argues that the hypothesis is, in fact, dispensable. If it is dropped, researchers can “meet the brain on its own terms” by searching for new, more adequate concepts to describe human brain organization. Neuroscientists can establish such concepts by conducting exploratory experiments that do not test particular cognitive hypotheses. The paper provides a systematic account of exploratory neuroscientific research that would allow researchers to form new concepts and formulate general principles of brain connectivity, and to combine connectivity studies with manipulation methods to identify neural entities in the brain. These research strategies would be most fruitful if applied to the mesoscopic scale of neuronal assemblies, since the organizational principles at this scale are currently largely unknown. This could help researchers to link microscopic and macroscopic evidence to provide a more comprehensive understanding of the human brain. The paper concludes by comparing this account of exploratory neuroscientific experiments to recent proposals for large-scale, discovery-based studies of human brain connectivity. (shrink)

Polysemous concepts with multiple related meanings pervade natural languages, yet some philosophers argue that we should eliminate them to avoid miscommunication and pointless debates in scientific discourse. This paper defends the legitimacy of polysemous concepts in science against this eliminativist challenge. My approach analyses such concepts as patchworks with multiple scale-dependent, technique-involving, domain-specific and property-targeting uses (patches). I demonstrate the generality of my approach by applying it to "hardness" in materials science, "homology" in evolutionary biology, "gold" in chemistry and "cortical (...) column" in neuroscience. Such patchwork concepts are legitimate if the techniques used to apply them produce reliable results, the domains to which they are applied are homogenous, and the properties they refer to are significant to describe, classify or explain the behavior of entities in the extension of the concept. By following these normative constraints, researchers can avoid miscommunication and pointless debates without having to eliminate polysemous patchwork concepts in scientific discourse. (shrink)

Philosophers of experiment have acknowledged that experiments are often more than mere hypothesis-tests, once thought to be an experiment's exclusive calling. Drawing on examples from contemporary biology, I make an additional amendment to our understanding of experiment by examining the way that `wide' instrumentation can, for reasons of efficiency, lead scientists away from traditional hypothesis-directed methods of experimentation and towards exploratory methods.

This paper provides an interpretation of Hans-Jörg Rheinberger’s notions of epistemic things and historical epistemology . I argue that Rheinberger’s approach articulates a unique contribution to current debates about integrated HPS, and I propose some modifications and extensions of this contribution. Drawing on examples from memory research, I show that Rheinberger is right to highlight a particular feature of many objects of empirical research (“epistemic things”)—especially in the contexts of exploratory experimentation—namely our lack of knowledge about them. I argue that (...) this analysis needs to be supplemented with an account of what scientists do know, and in particular, how they are able to attribute rudimentary empirical contours to objects of research. These contours are closely connected to paradigmatic research designs, which in turn are tied to basic methodological rules for the exploration of the purported phenomena. I suggest that we engage with such rules in order to develop our own normative (epistemological) categories, and I tie this proposal to the idea of a methodological naturalism in philosophy of science. (shrink)

Abstract“Sign stimuli” elicit specific patterns of behavior when an organism's motivation is appropriate. In the toad, visually released prey-catching involves orienting toward the prey, approaching, fixating, and snapping. For these action patterns to be selected and released, the prey must be recognized and localized in space. Toads discriminate prey from nonprey by certain spatiotemporal stimulus features. The stimulus-response relations are mediated by innate releasing mechanisms (RMs) with recognition properties partly modifiable by experience. Striato-pretecto-tectal connectivity determines the RM's recognition and localization (...) properties, whereas medialpallio-thalamo-tectal circuitry makes the system sensitive to changes in internal state and to prior history of exposure to stimuli. RMs encode the diverse stimulus conditions referring to the same prey object through different combinations of “specialized” tectal neurons, involving cells selectively tuned to prey features. The prey-selective neurons express the outcome of information processing in functional units consisting of interconnected cells. Excitatory and inhibitory interactions among feature-sensitive tectal and pretectal neurons specify the perceptual operations involved in distinguishing the prey from its background, selecting its features, and discriminating it from predators. Other connections indicate stimulus location. The results of these analyses are transmitted by specialized neurons projecting from the tectum to bulbar/spinal motor systems, providing a sensorimotor interface. Specific combinations of such projective neurons – mediating feature- and space-related messages – form “command releasing systems” that activate corresponding motor pattern generators for appropriate prey-catching action patterns. (shrink)

UNDERSTANDING SCIENTIFIC REASONING develops critical reasoning skills and guides students in the improvement of their scientific and technological literacy. The authors teach students how to understand and critically evaluate the scientific information they encounter in both textbooks and the popular media. With its focus on scientific pedagogy, UNDERSTANDING SCIENTIFIC REASONING helps students learn how to examine scientific reports with a reasonable degree of sophistication. The book also explains how to reason through case studies using the same informal logic skills employed (...) by scientists and to analyze a complex series of propositions and hypotheses using sound scientific reasoning. (shrink)

"Written with passionate conviction about the ethical uses of science, The Sun, the Genome, and the Internet is both a brilliant reinterpretation of the scientific process and a challenge to use new technologies to close, rather than widen, the gap between rich and poor."--BOOK JACKET.

In this powerful work of conceptual and analytical originality, the author argues for the primacy of the material arrangements of the laboratory in the dynamics of modern molecular biology. In a post-Kuhnian move away from the hegemony of theory, he develops a new epistemology of experimentation in which research is treated as a process for producing epistemic things. A central concern of the book is the basic question of how novelty is generated in the empirical sciences. In addressing this question, (...) the author brings French poststructuralist thinking—notably Jacques Derrida’s concepts of “différance” and “historiality”—to bear on the construction of epistemic things. Historiographical perspective shifts from the actors’ minds to their objects of manipulation. These epistemological and historical issues are illuminated in a detailed case study of a particular laboratory, that of the oncologist and biochemist Paul C. Zamecnik and his colleagues, located in a specific setting—the Collis P. Huntington Memorial Hospital of Harvard University at the Massachusetts General Hospital of Boston. The author traces how, between 1945 and 1965, this group developed an experimental system for synthesizing proteins in the test tube that put Zamecnik’s research team at the forefront of those who led biochemistry into the era of molecular biology. (shrink)

This book presents the concept of “complementary science” which contributes to scientific knowledge through historical and philosophical investigations. It emphasizes the fact that many simple items of knowledge that we take for granted were actually spectacular achievements obtained only after a great deal of innovative thinking, painstaking experiments, bold conjectures, and serious controversies. Each chapter in the book consists of two parts: a narrative part that states the philosophical puzzle and gives a problem-centred narrative on the historical attempts to solve (...) the puzzle; and the analysis part which provides in-depth analyses of certain scientific, historical, and philosophical aspects of the story. (shrink)

In this path-breaking work, Paul Thagard draws on history and philosophy of science, cognitive psychology, and the field of artificial intelligence to develop a ...

This 1983 book is a lively and clearly written introduction to the philosophy of natural science, organized around the central theme of scientific realism. It has two parts. 'Representing' deals with the different philosophical accounts of scientific objectivity and the reality of scientific entities. The views of Kuhn, Feyerabend, Lakatos, Putnam, van Fraassen, and others, are all considered. 'Intervening' presents the first sustained treatment of experimental science for many years and uses it to give a new direction to debates about (...) realism. Hacking illustrates how experimentation often has a life independent of theory. He argues that although the philosophical problems of scientific realism can not be resolved when put in terms of theory alone, a sound philosophy of experiment provides compelling grounds for a realistic attitude. A great many scientific examples are described in both parts of the book, which also includes lucid expositions of recent high energy physics and a remarkable chapter on the microscope in cell biology. (shrink)

Carl Craver investigates what we are doing when we sue neuroscience to explain what's going on in the brain.

There has been relatively little effort to provide a systematic overview of different forms of exploratory experimentation (EE). The present paper examines the growing subdiscipline of nanotoxicology and suggests that it illustrates at least four ways that researchers can engage in EE: searching for regularities; developing new techniques, simulation models, and instrumentation; collecting and analyzing large swaths of data using new experimental strategies (e.g., computer-based simulation and "high-throughput" instrumentation); and structuring an entire disciplinary field around exploratory research agendas. In order (...) to distinguish these and other activities more effectively, the paper proposes a taxonomy that includes three dimensions along which types of EE vary: (1) the aim of the experimental activity, (2) the role of theory in the activity, and (3) the methods or strategies employed for varying experimental parameters. (shrink)