Hierarchy or Heterarchy of Mammalian Circadian Timekeepers?

Mammalian circadian biologists commonly characterize the relation between circadian clocks as hierarchical, with the clock in the suprachiasmatic nucleus at the top of the hierarchy. The lineage of research since the suprachiasmatic nucleus (SCN) was first identified as in mammals has challenged this perspective, revealing clocks in peripheral tissues, showing that they respond to their own zeitgebers, coordinate oscillations among themselves, and in some cases modify the behavior of the SCN. Increasingly circadian timekeepers appear to constitute a heterarchical network, with control distributed and operating along multiple pathways.

Minding the gap: discovering the phenomenon of chemical transmission in the nervous system.

The neuron doctrine, according to which nerves consist of discontinuous neurons, presented investigators with the challenge of determining what activities occurred between them or between them and muscles. One group of researchers, dubbed the sparks, viewed the electrical current in one neuron as inducing a current in the next neuron or in muscles. For them there was no gap between the activities of neurons or neurons and muscles that required filling with a new type of activity.

Using neurons to maintain autonomy: Learning from C. elegans.

Understanding how biological organisms are autonomous-maintain themselves far from equilibrium through their own activities-requires understanding how they regulate those activities. In multicellular animals, such control can be exercised either via endocrine signaling through the vasculature or via neurons. In C.

Discovering autoinhibition as a design principle for the control of biological mechanisms.

Autoinhibition is a design principle realized in many molecular mechanisms in biology. After explicating the notion of a design principle and showing that autoinhibition is such a principle, we focus on how researchers discovered instances of autoinhibition, using research establishing the autoinhibition of the molecular motors kinesin and dynein as our case study. Research on kinesin and dynein began in the fashion described in accounts of mechanistic explanation but, once the mechanisms had been discovered, researchers discovered that they exhibited a second phenomenon, autoinhibition.

Reductionistic Explanations of Cognitive Information Processing: Bottoming Out in Neurochemistry.

A common motivation for engaging in reductionistic research is to ground explanations in the most basic processes operative in the mechanism responsible for the phenomenon to be explained. I argue for a different motivation-directing inquiry to the level of organization at which the components of a mechanism enable the work that results in the phenomenon. In the context of reductionistic accounts of cognitive information processing I argue that this requires going down to a level that is largely overlooked in these discussions, that of chemistry.

Figuring out what is happening: the discovery of two electrophysiological phenomena.

Research devoted to characterizing phenomena is underappreciated in philosophical accounts of scientific inquiry. This paper develops a diachronic analysis of research over 100 years that led to the recognition of two related electrophysiological phenomena, the membrane potential and the action potential. A diachronic perspective allows for reconciliation of two threads in philosophical discussions of phenomena-Hacking's treatment of phenomena as manifest in laboratory settings and Bogen and Woodward's construal of phenomena as regularities in the world.

Organization needs organization: Understanding integrated control in living organisms.

Organization figures centrally in the understanding of biological systems advanced by both new mechanists and proponents of the autonomy framework. The new mechanists focus on how components of mechanisms are organized to produce a phenomenon and emphasize productive continuity between these components. The autonomy framework focuses on how the components of a biological system are organized in such a way that they contribute to the maintenance of the organisms that produce them.

Grounding cognition: heterarchical control mechanisms in biology.

We advance an account that grounds cognition, specifically decision-making, in an activity all organisms as autonomous systems must perform to keep themselves viable-controlling their production mechanisms. Production mechanisms, as we characterize them, perform activities such as procuring resources from their environment, putting these resources to use to construct and repair the organism's body and moving through the environment. Given the variable nature of the environment and the continual degradation of the organism, these production mechanisms must be regulated by control mechanisms that select when a production is required and how it should be carried out.

Hierarchy and levels: analysing networks to study mechanisms in molecular biology.

Network representations are flat while mechanisms are organized into a hierarchy of levels, suggesting that the two are fundamentally opposed. I challenge this opposition by focusing on two aspects of the ways in which large-scale networks constructed from high-throughput data are analysed in systems biology: identifying clusters of nodes that operate as modules or mechanisms and using bio-ontologies such as gene ontology (GO) to annotate nodes with information about where entities appear in cells and the biological functions in which they participate. Of particular importance, GO organizes biological knowledge about cell components and functions hierarchically.

From parts to mechanisms: research heuristics for addressing heterogeneity in cancer genetics.

A major approach to cancer research in the late twentieth century was to search for genes that, when altered, initiated the development of a cell into a cancerous state (oncogenes) or failed to stop this development (tumor suppressor genes). But as researchers acquired the capacity to sequence tumors and incorporated the resulting data into databases, it became apparent that for many tumors no genes were frequently altered and that the genes altered in different tumors in the same tissue type were often distinct. To address this heterogeneity problem, many researchers looked to a higher level of organization-to mechanisms in which gene products (proteins) participated.

Sketching Biological Phenomena and Mechanisms.

In many fields of biology, both the phenomena to be explained and the mechanisms proposed to explain them are commonly presented in diagrams. Our interest is in how scientists construct such diagrams. Researchers begin with evidence, typically developed experimentally and presented in data graphs.

Using computational models to discover and understand mechanisms.

Areas of biology such as cell and molecular biology have been dominated by research directed at constructing mechanistic explanations that identify parts and operations that when organized appropriately are responsible for the various phenomena they investigate. Increasingly the mechanisms hypothesized involve non-sequential organization of non-linear operations and so exceed the ability of researchers to mentally rehearse their behavior. Accordingly, scientists rely on tools of computational modeling and dynamical systems theory in advancing dynamic mechanistic explanations.

Mechanists Must be Holists Too! Perspectives from Circadian Biology.

The pursuit of mechanistic explanations in biology has produced a great deal of knowledge about the parts, operations, and organization of mechanisms taken to be responsible for biological phenomena. Holist critics have often raised important criticisms of proposed mechanistic explanations, but until recently holists have not had alternative research strategies through which to advance explanations. This paper argues both that the results of mechanistic strategies has forced mechanists to confront ways in which whole systems affect their components and that new representational and modeling strategies are providing tools for understanding these effects of whole systems upon components.

Circadian Rhythms and Mood Disorders: Are the Phenomena and Mechanisms Causally Related?

This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent model for mania.

Can mechanistic explanation be reconciled with scale-free constitution and dynamics?

This paper considers two objections to explanations that appeal to mechanisms to explain biological phenomena. Marom argues that the time-scale on which many phenomena occur is scale-free. There is also reason to suspect that the network of interacting entities is scale-free.

The Non-Redundant Contributions of Marr's Three Levels of Analysis for Explaining Information-Processing Mechanisms.

Are all three of Marr's levels needed? Should they be kept distinct? We argue for the distinct contributions and methodologies of each level of analysis. It is important to maintain them because they provide three different perspectives required to understand mechanisms, especially information-processing mechanisms. The computational perspective provides an understanding of how a mechanism functions in broader environments that determines the computations it needs to perform (and may fail to perform).

From molecules to behavior and the clinic: Integration in chronobiology.

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer.

Dynamic mechanistic explanation: computational modeling of circadian rhythms as an exemplar for cognitive science.

We consider computational modeling in two fields: chronobiology and cognitive science. In circadian rhythm models, variables generally correspond to properties of parts and operations of the responsible mechanism. A computational model of this complex mechanism is grounded in empirical discoveries and contributes a more refined understanding of the dynamics of its behavior.

Dynamical models: an alternative or complement to mechanistic explanations?

While agreeing that dynamical models play a major role in cognitive science, we reject Stepp, Chemero, and Turvey's contention that they constitute an alternative to mechanistic explanations. We review several problems dynamical models face as putative explanations when they are not grounded in mechanisms. Further, we argue that the opposition of dynamical models and mechanisms is a false one and that those dynamical models that characterize the operations of mechanisms overcome these problems.

The cell: locus or object of inquiry?

Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell.

How can philosophy be a true cognitive science discipline?

Although philosophy has been only a minor contributor to cognitive science to date, this paper describes two projects in naturalistic philosophy of mind and one in naturalistic philosophy of science that have been pursued during the past 30 years and that can make theoretical and methodological contributions to cognitive science. First, stances on the mind-body problem (identity theory, functionalism, and heuristic identity theory) are relevant to cognitive science as it negotiates its relation to neuroscience and cognitive neuroscience. Second, analyses of mental representations address both their vehicles and their contents; new approaches to characterizing how representations have content are particularly relevant to understanding the relation of cognitive agents to their environments.

Constructing a philosophy of science of cognitive science.

Philosophy of science is positioned to make distinctive contributions to cognitive science by providing perspective on its conceptual foundations and by advancing normative recommendations. The philosophy of science I embrace is naturalistic in that it is grounded in the study of actual science. Focusing on explanation, I describe the recent development of a mechanistic philosophy of science from which I draw three normative consequences for cognitive science.

In search of mitochondrial mechanisms: interfield excursions between cell biology and biochemistry.

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the role of the mitochondrion and its component parts in cellular respiration.