Biomedical subjects

William B Kristan

Publications and source records attributed to William B Kristan.

13 recordsLinked to original sources

PubMed2006

Imaging dedicated and multifunctional neural circuits generating distinct behaviors.

Central pattern generators (CPGs) control both swimming and crawling in the medicinal leech. To investigate whether the neurons comprising these two CPGs are dedicated or multifunctional, we used voltage-sensitive dye imaging to record from approximately 80% of the approximately 400 neurons in a segmental ganglion. By eliciting swimming and crawling in the same preparation, we were able to identify neurons that participated in either of the two rhythms, or both. More than twice as many cells oscillated in-phase with crawling (188) compared with swimming (90). Surprisingly, 84 of the cells (93%) that oscillated with swimming also oscillated with crawling. We then characterized two previously unidentified interneurons, cells 255 and 257, that had interesting activity patterns based on the imaging results. Cell 255 proved to be a multifunctional interneuron that oscillates with and can perturb both rhythms, whereas cell 257 is an interneuron dedicated to crawling. These results show that the swimming and crawling networks are driven by both multifunctional and dedicated circuitry.

Animals↗

PubMed2006

Form and function in systems neuroscience.

'Form follows function' is an architectural philosophy attributed to the great American architect Louis Sullivan, and later taken up by the Bauhaus movement. It stresses that the form of a building should reflect its function. Neuroscientists have used the converse of this dictum to learn the functions of neural circuits, believing that if we study neural architecture, it will lead us to an understanding of how neural systems function. New tools for studying the structure of neural circuits are being developed, so it is important to discuss what the old techniques have taught us about how to derive function from the form of a neural circuit.

Animals↗

PubMed2006

Encoding and decoding touch location in the leech CNS.

Spike times encode stimulus values in many sensory systems, but it is generally unknown whether such temporal variations are decoded (i.e., whether they influence downstream networks that control behavior). In the present study, we directly address this decoding problem by quantifying both sensory encoding and decoding in the leech. By mechanically stimulating the leech body wall while recording from mechanoreceptors, we show that pairs of leech sensory neurons with overlapping receptive fields encode touch location by their relative latencies, number of spikes, and instantaneous firing rates, with relative latency being the most accurate indicator of touch location. We then show that the relative latency and count are decoded by manipulating these variables in sensory neuron pairs while simultaneously monitoring the resulting behavior. Although both variables are important determinants of leech behavior, the decoding mechanisms are more sensitive to changes in relative spike count than changes in relative latency.

Action Potentials↗

PubMed2006

From crawling to cognition: analyzing the dynamical interactions among populations of neurons.

By using multi-electrode arrays or optical imaging, investigators can now record from many individual neurons in various parts of nervous systems simultaneously while an animal performs sensory, motor or cognitive tasks. Given the large multidimensional datasets that are now routinely generated, it is often not obvious how to find meaningful results within the data. The analysis of neuronal-population recordings typically involves two steps: the extraction of relevant dynamics from neural data, and then use of the dynamics to classify and discriminate features of a stimulus or behavior. We focus on the application of techniques that emphasize interactions among the recorded neurons rather than using just the correlations between individual neurons and a perception or a behavior. An understanding of modern analysis techniques is crucially important for researchers interested in the co-varying activity among populations of neurons or even brain regions.

Action Potentials↗

PubMed2006

Functions of the subesophageal ganglion in the medicinal leech revealed by ablation of neuromeres in embryos.

Two general trends in the evolution of the nervous system have been toward centralization of neuronal somata and cephalization of the central nervous system (CNS). These organizational trends are apparent in the nervous system of annelid worms, including leeches. To determine if the anterior brain of the leech serves functions similar to those of the brains of more complex organisms, including vertebrates, we ablated one of the two major regions of the cephalic brain--the subesophageal ganglion (SubEG). For anatomical reasons, ablations were performed in embryos, rather than in adults. At the end of embryonic development, we observed the leeches' spontaneous behaviour and their responses to moderate touch. We observed that, although the midbody ganglia of the leech CNS display a high degree of local autonomy, the cephalic brain provides generalized excitation to the rest of the CNS, is a source of selective inhibition that modulates behaviour, integrates sensory information from the head with signals from the rest of the body, and plays an important role in organizing at least some complicated whole-body behaviours. These roles of the leech cephalic brain are common features of brain function in many organisms, and our results are consistent with the hypothesis that they arose early in evolution and have been conserved in complex nervous systems.

Animals↗

PubMed2005

Neuronal control of leech behavior.

The medicinal leech has served as an important experimental preparation for neuroscience research since the late 19th century. Initial anatomical and developmental studies dating back more than 100 years ago were followed by behavioral and electrophysiological investigations in the first half of the 20th century. More recently, intense studies of the neuronal mechanisms underlying leech movements have resulted in detailed descriptions of six behaviors described in this review; namely, heartbeat, local bending, shortening, swimming, crawling, and feeding. Neuroethological studies in leeches are particularly tractable because the CNS is distributed and metameric, with only 400 identifiable, mostly paired neurons in segmental ganglia. An interesting, yet limited, set of discrete movements allows students of leech behavior not only to describe the underlying neuronal circuits, but also interactions among circuits and behaviors. This review provides descriptions of six behaviors including their origins within neuronal circuits, their modification by feedback loops and neuromodulators, and interactions between circuits underlying with these behaviors.

Animals↗

PubMed2005

Embryonic electrical connections appear to pre-figure a behavioral circuit in the leech CNS.

During development, many embryos show electrical coupling among neurons that is spatially and temporally regulated. For example, in vertebrate embryos extensive dye coupling is seen during the period of circuit formation, suggesting that electrical connections could pre-figure circuits, but it has been difficult to identify which neuronal types are coupled. We have used the leech Hirudo medicinalis to follow the development of electrical connections within the circuit that produces local bending. This circuit consists of three layers of neurons: four mechanosensory neurons (P cells), 17 identified interneurons, and approximately 24 excitatory and inhibitory motor neurons. These neurons can be identified in embryos, and we followed the spatial and temporal dynamics as specific connections developed. Injecting Neurobiotin into identified cells of the circuit revealed that electrical connections were established within this circuit in a precise manner from the beginning. Connections first appeared between motor neurons; mechanosensory neurons and interneurons started to connect at least a day later. This timing correlates with the development of behaviors, so the pattern of emerging connectivity could explain the appearance first of spontaneous behaviors (driven by a electrically coupled motor network) and then of evoked behaviors (when sensory neurons and interneurons are added to the circuit).

Animals↗

PubMed2005

Sequential development of electrical and chemical synaptic connections generates a specific behavioral circuit in the leech.

Neuronal circuits form during embryonic life, even before synapses are completely mature. Developmental changes can be quantitative (e.g., connections become stronger and more reliable) or qualitative (e.g., synapses form, are lost, or switch from electrical to chemical or from excitatory to inhibitory). To explore how these synaptic events contribute to behavioral circuits, we have studied the formation of a circuit that produces local bending (LB) behavior in leech embryos. This circuit is composed of three layers of neurons: mechanosensory neurons, interneurons, and motor neurons. The only inhibition in this circuit is in the motor neuron layer; it allows the animal to contract on one side while relaxing the opposite side. LB develops in two stages: initially touching the body wall causes circumferential indentation (CI), an embryonic behavior in which contraction takes place around the whole perimeter of the segment touched; one or 2 d later, the same touch elicits adult-like LB. Application of bicuculline methiodide in embryos capable of LB switched the behavior back into CI, indicating that the development of GABAergic connections turns CI into LB. Using voltage-sensitive dyes and electrophysiological recordings, we found that electrical synapses were present early and produced CI. Inhibition appeared later, shaping the circuit that was already connected by electrical synapses and producing the adult behavior, LB.

Animals↗

PubMed2005

Location and intensity discrimination in the leech local bend response quantified using optic flow and principal components analysis.

In response to touches to their skin, medicinal leeches shorten their body on the side of the touch. We elicited local bends by delivering precisely controlled pressure stimuli at different locations, intensities, and durations to body-wall preparations. We video-taped the individual responses, quantifying the body-wall displacements over time using a motion-tracking algorithm based on making optic flow estimates between video frames. Using principal components analysis (PCA), we found that one to three principal components fit the behavioral data much better than did previous (cosine) measures. The amplitudes of the principal components (i.e., the principal component scores) nicely discriminated the responses to stimuli both at different locations and of different intensities. Leeches discriminated (i.e., produced distinguishable responses) between touch locations that are approximately a millimeter apart. Their ability to discriminate stimulus intensity depended on stimulus magnitude: discrimination was very acute for weak stimuli and less sensitive for stronger stimuli. In addition, increasing the stimulus duration improved the leech's ability to discriminate between stimulus intensities. Overall, the use of optic flow fields and PCA provide a powerful framework for characterizing the discrimination abilities of the leech local bend response.

Animals↗

PubMed2005

Quantifying stimulus discriminability: a comparison of information theory and ideal observer analysis.

Performance in sensory discrimination tasks is commonly quantified using either information theory or ideal observer analysis. These two quantitative frameworks are often assumed to be equivalent. For example, higher mutual information is said to correspond to improved performance of an ideal observer in a stimulus estimation task. To the contrary, drawing on and extending previous results, we show that five information-theoretic quantities (entropy, response-conditional entropy, specific information, equivocation, and mutual information) violate this assumption. More positively, we show how these information measures can be used to calculate upper and lower bounds on ideal observer performance, and vice versa. The results show that the mathematical resources of ideal observer analysis are preferable to information theory for evaluating performance in a stimulus discrimination task. We also discuss the applicability of information theory to questions that ideal observer analysis cannot address.

Algorithms↗

PubMed2003

Imaging reveals synaptic targets of a swim-terminating neuron in the leech CNS.

In the leech, the command-like neuron called cell Tr2 is known to stop swimming, but the connections from cell Tr2 to the swim central pattern generator have not been identified. We used fluorescence resonance energy transfer voltage-sensitive dyes to identify three neurons that are synaptic targets of cell Tr2. We then used electrophysiological techniques to show that these connections are monosynaptic, chemical, and excitatory. Two of the novel targets, cell 256 and cell 54, terminate swimming when stimulated. These neurons are likely to mediate swim cessation caused by cell Tr2 activity, and thus play the role of intermediate control cells in the leech CNS.

Animals↗

PubMed2002

Evidence for sequential decision making in the medicinal leech.

Decision making can be a complex task involving a sequence of subdecisions. For example, we decide to pursue a goal (e.g., get something to eat), then decide how to accomplish that goal (e.g., go to a restaurant), and then make a sequence of more specific plans (e.g., which restaurant to go to, how to get there, what to order, etc.). In characterizing the effects of stimulating individual brain neurons in the isolated nervous system of the leech Hirudo medicinalis, we have found evidence that leeches also make decisions sequentially. In this study, we describe a pair of interneurons that elicited locomotory motor programs, either swimming or crawling, in isolated nerve cords. In semi-intact animals, stimulating the same neurons also produced either swimming or crawling, and which behavior was produced could be controlled experimentally by manipulating the depth of saline around the intact part of the leech. These same neurons were excited and fired strongly when swimming or crawling occurred spontaneously or in response to mechanosensory stimulation. We conclude that these brain interneurons help to decide on locomotion (i.e., they are "locomotory command-like neurons") and that the ultimate behavior is determined downstream, in a part of the decision-making hierarchy that monitors stimuli related to the depth of fluid surrounding the leech.

Animals↗

PubMed2002

Analysis of oscillations in a reciprocally inhibitory network with synaptic depression.

We present and analyze a model of a two-cell reciprocally inhibitory network that oscillates. The principal mechanism of oscillation is short-term synaptic depression. Using a simple model of depression and analyzing the system in certain limits, we can derive analytical expressions for various features of the oscillation, including the parameter regime in which stable oscillations occur, as well as the period and amplitude of these oscillations. These expressions are functions of three parameters: the time constant of depression, the synaptic strengths, and the amount of tonic excitation the cells receive. We compare our analytical results with the output of numerical simulations and obtain good agreement between the two. Based on our analysis, we conclude that the oscillations in our network are qualitatively different from those in networks that oscillate due to postinhibitory rebound, spike-frequency adaptation, or other intrinsic (rather than synaptic) adaptational mechanisms. In particular, our network can oscillate only via the synaptic escape mode of Skinner, Kopell, and Marder (1994).

Animals↗