Miranda J. Cullins

The significance of dynamical architecture for adaptive responses to mechanical loads during rhythmic behavior

Many behaviors require reliably generating sequences of motor activity while adapting the activity to incoming sensory information. This process has often been conceptually explained as either fully dependent on sensory input (a chain reflex) or fully independent of sensory input (an idealized central pattern generator, or CPG), although the consensus of the field is that most neural pattern generators lie somewhere between these two extremes. Many mathematical models of neural pattern generators use limit cycles to generate the sequence of behaviors, but other models, such as a heteroclinic channel (an attracting chain of saddle points), have been suggested. To explore the range of intermediate behaviors between CPGs and chain reflexes, in this paper we describe a nominal model of swallowing in Aplysia californica. Depending upon the value of a single parameter, the model can transition from a generic limit cycle regime to a heteroclinic regime (where the trajectory slows as it passes near saddle points). We then study the behavior of the system in these two regimes and compare the behavior of the models with behavior recorded in the animal in vivo and in vitro. We show that while both pattern generators can generate similar behavior, the stable heteroclinic channel can better respond to changes in sensory input induced by load, and that the response matches the changes seen when a load is added in vivo. We then show that the underlying stable heteroclinic channel architecture exhibits dramatic slowing of activity when sensory and endogenous input is reduced, and show that similar slowing with removal of proprioception is seen in vitro. Finally, we show that the distributions of burst lengths seen in vivo are better matched by the distribution expected from a system operating in the heteroclinic regime than that expected from a generic limit cycle. These observations suggest that generic limit cycle models may fail to capture key aspects of Aplysia feeding behavior, and that alternative architectures such as heteroclinic channels may provide better descriptions.

Motor neuronal activity varies least among individuals when it matters most for behavior

How does motor neuronal variability affect behavior? To explore this question, we quantified activity of multiple individual identified motor neurons mediating biting and swallowing in intact, behaving Aplysia californica by recording from the protractor muscle and the three nerves containing the majority of motor neurons controlling the feeding musculature. We measured multiple motor components: duration of the activity of identified motor neurons as well as their relative timing. At the same time, we measured behavioral efficacy: amplitude of grasping movement during biting and amplitude of net inward food movement during swallowing. We observed that the total duration of the behaviors varied: Within animals, biting duration shortened from the first to the second and third bites; between animals, biting and swallowing durations varied. To study other sources of variation, motor components were divided by behavior duration (i.e., normalized). Even after normalization, distributions of motor component durations could distinguish animals as unique individuals. However, the degree to which a motor component varied among individuals depended on the role of that motor component in a behavior. Motor neuronal activity that was essential for the expression of biting or swallowing was similar among animals, whereas motor neuronal activity that was not essential for that behavior varied more from individual to individual. These results suggest that motor neuronal activity that matters most for the expression of a particular behavior may vary least from individual to individual. Shaping individual variability to ensure behavioral efficacy may be a general principle for the operation of motor systems.

Electrode fabrication and implantation in Aplysia californica for multi-channel neural and muscular recordings in intact, freely behaving animals.

Recording from key nerves and muscles of Aplysia during feeding behavior allows us to study the patterns of neural control in an intact animal. Simultaneously recording from multiple nerves and muscles gives us precise information about the timing of neural activity. Previous recording methods have worked for two electrodes, but the study of additional nerves or muscles required combining and averaging the recordings of multiple animals, which made it difficult to determine fine details of timing and phasing, because of variability from response to response, and from animal to animal. Implanting four individual electrodes has a very low success rate due to the formation of adhesions that prevent animals from performing normal feeding movements. We developed a new method of electrode fabrication that reduces the bulk of the electrodes inside the animal allowing for normal feeding movements. Using a combination of glues to attach the electrodes results in a more reliable insulation of the electrode which lasts longer, making it possible to record for periods as long as a week. The fabrication technique that we describe could be extended to incorporate several additional electrodes, and would be applicable to vertebrate animals.

Preparing the Periphery for a Subsequent Behavior: Motor Neuronal Activity during Biting Generates Little Force but Prepares a Retractor Muscle to Generate Larger Forces during Swallowing in Aplysia

Some behaviors occur in obligatory sequence, such as reaching before grasping an object. Can the earlier behavior serve to prepare the musculature for the later behavior? If it does, what is the underlying neural mechanism of the preparation? To address this question, we examined two feeding behaviors in the marine mollusk Aplysia californica, one of which must precede the second: biting and swallowing. Biting is an attempt to grasp food. When that attempt is successful, the animal immediately switches to swallowing to ingest food. The main muscle responsible for pulling food into the buccal cavity during swallowing is the I3 muscle, whose motor neurons B6, B9, and B3 have been previously identified. By performing recordings from these neurons in vivo in intact, behaving animals or in vitro in a suspended buccal mass preparation, we demonstrated that the frequencies and durations of these motor neurons increased from biting to swallowing. Using the physiological patterns of activation to drive these neurons intracellularly, we further demonstrated that activating them using biting-like frequencies and durations, either alone or in combination, generated little or no force in the I3 muscle. When biting-like patterns preceded swallowing-like patterns, however, the forces during the subsequent swallowing-like patterns were significantly enhanced. Sequences of swallowing-like patterns, either with these neurons alone or in combination, further enhanced forces in the I3 muscle. These results suggest a novel mechanism for enhancing force production in a muscle, and may be relevant to understanding motor control in vertebrates.

Wavelet-based neural pattern analyzer for behaviorally significant burst pattern recognition

Closed-loop neural prosthesis systems rely on accurately recording neural data from multiple neurons and detecting behaviorally meaningful patterns before representing them in a highly compressed form for wireless transmission over a limited-bandwidth link. We present a novel wavelet-based approach for detecting spikes, grouping them as bursts and building a dynamic vocabulary of meaningful burst patterns. Simulation results on pre-recorded in vivo multi-channel extracellular neural data from the buccal ganglion of Aplysia demonstrate the feasibility of behavior recognition as well as data compression (> 500X) by the proposed approach.

Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function

To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californicas feeding system. This muscle mediates retraction of Aplysias food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38s activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38s typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysias generation of multifunctionality.

Sensory Feedback Reduces Individuality by Increasing Variability within Subjects

Behavioral variability is ubiquitous [1-6], yet variability is more than just noise. Indeed, humans exploit their individual motor variability to improve tracing and reaching tasks [7]. What controls motor variability? Increasing the variability of sensory input, or applying force perturbations during a task, increases task variability [8, 9]. Sensory feedback may also increase task-irrelevant variability [9, 10]. In contrast, sensory feedback during locust flight or to multiple cortical areas just prior to task performance decreases variability during task-relevant motor behavior [11, 12]. Thus, how sensory feedback affects both task-relevant and task-irrelevant motor outputs must be understood. Furthermore, since motor control is studied in populations, the effects of sensory feedback on variability must also be understood within and across subjects. For example, during locomotion, each step may vary within and across individuals, even when behavior is normalized by step cycle duration [13]. Our previous work demonstrated that motor components that matter for effective behavior show less individuality [14]. Is sensory feedback the mechanism for reducing individuality? We analyzed durations and relative timings of motor pools within swallowing motor patterns in the presence and absence of sensory feedback and related these motor program components to behavior. Here, at the level of identified motor neurons, we show that sensory feedback to motor program components highly correlated with behavioral efficacy reduces variability across subjects but-surprisingly-increases variability within subjects. By controlling intrinsic, individual differences in motor neuronal activity, sensory feedback provides each subject access to a common solution space.