Klaudiusz R. Weiss
- PROFESSOR Neuroscience
- PROFESSOR Structural and Chemical Biology
Ph.D., State University of New York
Cellular Mechanisms of Behavioral PlasticityWe use a multidisciplinary approach that combines behavioral, morphological, electrophysiological, cell biological and molecular-biological techniques to explain the neural basis of those forms of behavioral plasticity that are due to changes in the motivational state of animals.
In view of the complexity of these questions, we have chosen to ask them in a preparation that has a relatively simple nervous system - the marine mollusc Aplysia californica. The central nervous system of this animal is distributed into several ganglia, each of which consists of a limited number of neurons, many of which are large and easily identifiable as unique individuals. The ability to recognize the same neurons from animal to animal has greatly facilitated the functional characterization of individual cells as sensory neurons, motor neurons and interneurons. This in turn has allowed the reconstruction of neuronal circuits that mediate a variety of behaviors.
Our laboratory has been using the feeding behavior of Aplysia to determine the cellular mechanisms that are responsible for those forms of behavioral plasticity that result from changes in the level of hunger and arousal of the animal. Circuit-level analysis has provided new insights into the organization of neuronal networks into mediating and modulatory systems and led to a new conceptualization of command neurons. Studies of transmitters and modulators involved in the regulation of behavior have resulted in purification and sequencing of several novel neuropeptides and to molecular cloning of the mRNA of these molecules. These neuropeptides have now been localized to specific neurons, and shown to act as cotransmitters. To a large extent our research is now focused on the role that these peptidergic cotransmitters play in optimizing the efficiency of behavior in response to changes in the motivational state of the animal. We are particularly interested in determining:
We expect that this approach will yield a unified picture in which our understanding of behavioral plasticity will extend all the way from behavior to the molecules involved.
Chang DJ, Li XC, Lee YS, Kim HK, Kim US, Cho NJ, Lo X, Weiss K, Kandel ER, Kaang BK. Activation of a heterologously expressed octopamine receptor coupled only to adenylyl cyclase produces all the features of presynaptic facilitation in aplysia sensory neurons. Proc Natl Acad Sci U S A 2000 Feb 15; 97(4): 1829-34.
Brezina V, Church P, Weiss K. Temporal pattern dependence of neuronal peptide transmitter release: models and experiments. J Neurosci 2000 Sep 15; 20(18): 6760-72.In this paper we construct, on the basis of existing experimental data, a mathematical model of firing-elicited release of peptide transmitters from motor neuron B15 in the accessory radula closer neuromuscular system of Aplysia. The model consists of a slow "mobilizing" reaction and the fast release reaction itself. Experimentally, however, it was possible to measure only the mean, heavily averaged release, lacking fast kinetic information. Considered in the conventional way, the data were insufficient to completely specify the details of the model, in particular the relative properties of the slow and the unobservable fast reaction. We illustrate here, with our model and with additional experiments, how to approach such a problem by considering another dimension of release, namely its pattern dependence. The mean release is sensitive to the temporal pattern of firing, even to pattern on time scales much faster than the time scale on which the release is averaged. The mean release varies with the time scale and magnitude of the pattern, relative to the time scale and nonlinearity of the release reactions with which the pattern interacts. The type and magnitude of pattern dependence, especially when correlated systematically over a range of patterns, can therefore yield information about the properties of the release reactions. Thus, temporal pattern can be used as a probe of the release process, even of its fast, directly unobservable components. More generally, the analysis provides insights into the possible ways in which such pattern dependence, widespread especially in neuropeptide- and hormone-releasing systems, might arise from the properties of the underlying cellular reactions.
Klein AN, Weiss K, Cropper E. Glutamate is the fast excitatory neurotransmitter of small cardioactive peptide-containing Aplysia radula mechanoafferent neuron B21. Neurosci Lett 2000 Jul 28; 289(1): 37-40.
Vilim F, Cropper E, Price DA, Kupfermann I, Weiss K. Peptide cotransmitter release from motorneuron B16 in aplysia californica: costorage, corelease, and functional implications. J Neurosci 2000 Mar 1; 20(5): 2036-42.
Morgan PT, Perrins R, Looyd PE, Weiss K. Intrinsic and extrinsic modulation of a single central pattern generating circuit. J Neurophysiol 2000 Sep; 84(3): 1186-93.
Orekhova IV, Weiss K. Optimization of rhythmic behaviors by modulation of the neuromuscular transform. J Neurophysiol 2000 Jan; 83(1): 260-79.We conclude our study of the properties and the functional role of the neuromuscular transform (NMT). The NMT is an input-output relation that formalizes the processes by which patterns of motor neuron firing are transformed to muscle contractions. Because the NMT acts as a dynamic, nonlinear, and modifiable filter, the transformation is complex. In the two preceding papers we developed a framework for analysis of the NMT and identified with it principles by which the NMT transforms different firing patterns to contractions. We then saw that, with fixed properties, the NMT significantly constrains the production of functional behavior. Many desirable behaviors are not possible with any firing pattern. Here we examine, theoretically as well as experimentally in the accessory radula closer (ARC) neuromuscular system of Aplysia, how this constraint is alleviated by making the properties of the NMT variable by neuromuscular plasticity and modulation. These processes dynamically tune the properties of the NMT to match the desired behavior, expanding the range of behaviors that can be produced. For specific illustration, we continue to focus on the relation between the speed of the NMT and the speed of cyclical, rhythmic behavior. Our analytic framework emphasizes the functional distinction between intrinsic plasticity or modulation of the NMT, dependent, like the contraction itself, on the motor neuron firing pattern, and extrinsic modulation, independent of it. The former is well suited to automatically optimizing the performance of a single behavior; the latter, to multiplying contraction shapes for multiple behaviors. In any case, to alleviate the constraint of the NMT, the plasticity and modulation must be peripheral. Such processes are likely to play a critical role wherever the nervous system must command, through the constraint of the NMT, a broad range of functional behaviors.
Weiss K. The neuromuscular transform constrains the production of functional rhythmic behaviors. J Neurophysiol 2000 Jan; 83(1): 232-59.We continue our study of the properties and the functional role of the neuromuscular transform (NMT). The NMT is an input-output relation that formalizes the processes by which patterns of motor neuron firing are transformed to muscle contractions. Because the NMT acts as a dynamic, nonlinear, and modifiable filter, the transformation is complex. In the preceding paper we developed a framework for analysis of the NMT and identified with it principles by which the NMT transforms different firing patterns to contractions. The ultimate question is functional, however. In sending different firing patterns through the NMT, the nervous system is seeking to command different functional behaviors, with specific contraction requirements. To what extent do the contractions that emerge from the NMT actually satisfy those requirements? In this paper we extend our analysis to address this issue. We define representative behavioral tasks and corresponding measures of performance, for a single neuromuscular unit, for two antagonistic units, and, in a real illustration, for the accessory radula closer (ARC)-opener neuromuscular system of Aplysia. We focus on cyclical, rhythmic behaviors which reveal the underlying principles particularly clearly. We find that, although every pattern of motor neuron firing produces some state of muscle contraction, only a few patterns produce functional behavior, and even fewer produce efficient functional behavior. The functional requirements thus dictate certain patterns to the nervous system. But many desirable functional behaviors are not possible with any pattern. We examine, in particular, how rhythmic behaviors degrade and disintegrate as the nervous system attempts to speed up their cycle frequency. This happens because, with fixed properties, the NMT produces only a limited range of contraction shapes that are kinetically well matched to the firing pattern only on certain time scales. Thus the properties of the NMT constrain and restrict the production of functional behaviors. In the following paper, we see how the constraint may be alleviated and the range of functional behaviors expanded by appropriately tuning the properties of the NMT through neuromuscular plasticity and modulation.
Brezina V, Orekhova IV, Weiss K. The neuromuscular transform: the dynamic, nonlinear link between motor neuron firing patterns and muscle contraction in rhythmic behaviors. J Neurophysiol 2000 Jan; 83(1): 207-31.The nervous system issues motor commands to muscles to generate behavior. All such commands must, however, pass through a filter that we call here the neuromuscular transform (NMT). The NMT transforms patterns of motor neuron firing to muscle contractions. This work is motivated by the fact that the NMT is far from being a straightforward, transparent link between motor neuron and muscle. The NMT is a dynamic, nonlinear, and modifiable filter. Consequently motor neuron firing translates to muscle contraction in a complex way. This complexity must be taken into account by the nervous system when issuing its motor commands, as well as by us when assessing their significance. This is the first of three papers in which we consider the properties and the functional role of the NMT. Physiologically, the motor neuron-muscle link comprises multiple steps of presynaptic and postsynaptic Ca(2+) elevation, transmitter release, and activation of the contractile machinery. The NMT formalizes all these into an overall input-output relation between patterns of motor neuron firing and shapes of muscle contractions. We develop here an analytic framework, essentially an elementary dynamical systems approach, with which we can study the global properties of the transformation. We analyze the principles that determine how different firing patterns are transformed to contractions, and different parameters of the former to parameters of the latter. The key properties of the NMT are its nonlinearity and its time dependence, relative to the time scale of the firing pattern. We then discuss issues of neuromuscular prediction, control, and coding. Does the firing pattern contain a code by means of which particular parameters of motor neuron firing control particular parameters of muscle contraction? What information must the motor neuron, and the nervous system generally, have about the periphery to be able to control it effectively? We focus here particularly on cyclical, rhythmic contractions which reveal the principles particularly clearly. Where possible, we illustrate the principles in an experimentally advantageous model system, the accessory radula closer (ARC)-opener neuromuscular system of Aplysia. In the following papers, we use the framework developed here to examine how the properties of the NMT govern functional performance in different rhythmic behaviors that the nervous system may command.
Orekhova IV, Jing J, Brezina V, Dicaprio RA, Weiss K, Cropper EC. Sonometric measurements of motor-neuron-evoked movements of an internal feeding structure (the radula) in Aplysia. J Neurophysiol 2001 Aug; 86(2): 1057-1061.
Dembrow N, Jing J, Proekt A, Romero A, Vilim F, Cropper E, Weiss K. A newly identified buccal interneuron initiates and modulates feeding motor programs in aplysia. J Neurophysiol. 2003 Oct; 90(4): 2190-240.
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Dr. Weiss did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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