Aplysia Feeding Network Research Articles

A computational neural model that incorporates both intrinsic dynamics and sensory feedback in the Aplysia feeding network

Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding.

Variable task switching in the feeding network of Aplysia is a function of differential command input.

Command systems integrate sensory information and then activate the interneurons and motor neurons that mediate behavior. Much research has established that the higher-order projection neurons that constitute these systems can play a key role in specifying the nature of the motor activity induced, or determining its parametric features. To a large extent, these insights have been obtained by contrasting activity induced by stimulating one neuron (or set of neurons) to activity induced by stimulating a different neuron (or set of neurons). The focus of our work differs. We study one type of motor program, ingestive feeding in the mollusc Aplysia californica, which can either be triggered when a single projection neuron (CBI-2) is repeatedly stimulated or can be triggered by projection neuron coactivation (e.g., activation of CBI-2 and CBI-3). We ask why this might be an advantageous arrangement. The cellular/molecular mechanisms that configure motor activity are different in the two situations because the released neurotransmitters differ. We focus on an important consequence of this arrangement, the fact that a persistent state can be induced with repeated CBI-2 stimulation that is not necessarily induced by CBI-2/3 coactivation. We show that this difference can have consequences for the ability of the system to switch from one type of activity to another.NEW & NOTEWORTHY We study a type of motor program that can be induced either by stimulating a higher-order projection neuron that induces a persistent state, or by coactivating projection neurons that configure activity but do not produce a state change. We show that when an activity is configured without a state change, it is possible to immediately return to an intermediate state that subsequently can be converted to any type of motor program.

Repetition priming of motor activity mediated by a central pattern generator: the importance of extrinsic vs. intrinsic program initiators.

Repetition priming is characterized by increased performance as a behavior is repeated. Although this phenomenon is ubiquitous, mediating mechanisms are poorly understood. We address this issue in a model system, the feeding network of Aplysia This network generates both ingestive and egestive motor programs. Previous data suggest a chemical coding model: ingestive and egestive inputs to the feeding central pattern generator (CPG) release different modulators, which act via different second messengers to prime motor activity in different ways. The ingestive input to the CPG (neuron CBI-2) releases the peptides feeding circuit activating peptide and cerebral peptide 2, which produce an ingestive pattern of activity. The egestive input to the CPG (the esophageal nerve) releases the peptide small cardioactive peptide. This model is based on research that focused on a single aspect of motor control (radula opening). Here we ask whether repetition priming is observed if activity is triggered with a neuron within the core CPG itself and demonstrate that it is not. Moreover, previous studies demonstrated that effects of modulatory neurotransmitters that induce repetition priming persist. This suggests that it should be possible to "prime" motor programs triggered from within the CPG by first stimulating extrinsic modulatory inputs. We demonstrate that programs triggered after ingestive input activation are ingestive and programs triggered after egestive input activation are egestive. We ask where this priming occurs and demonstrate modifications within the CPG itself. This arrangement is likely to have important consequences for "task" switching, i.e., the cessation of one type of motor activity and the initiation of another.

Repetition priming-induced changes in sensorimotor transmission.

When a behavior is repeated performance often improves, i.e., repetition priming occurs. Although repetition priming is ubiquitous, mediating mechanisms are poorly understood. We address this issue in the feeding network ofAplysia Similar to the priming observed elsewhere, priming inAplysiais stimulus specific, i.e., it can be either "ingestive" or "egestive." Previous studies demonstrated that priming alters motor and premotor activity. Here we sought to determine whether sensorimotor transmission is also modified. We report that changes in sensorimotor transmission do occur. We ask how they are mediated and obtain data that strongly suggest a presynaptic mechanism that involves changes in the "background" intracellular Ca(2+)concentration ([Ca(2+)]i) in primary afferents themselves. This form of plasticity has previously been described and generated interest due to its potentially graded nature. Manipulations that alter the magnitude of the [Ca(2+)]iimpact the efficacy of synaptic transmission. It is, however, unclear how graded control is exerted under physiologically relevant conditions. In the feeding system changes in the background [Ca(2+)]iare mediated by the induction of a nifedipine-sensitive current. We demonstrate that the extent to which this current is induced is altered by peptides (i.e., increased by a peptide released during the repetition priming of ingestive activity and decreased by a peptide released during the repetition priming of egestive activity). We suggest that this constitutes a behaviorally relevant mechanism for the graded control of synaptic transmission via the regulation of the [Ca(2+)]iin a neuron.

Specificity of repetition priming: the role of chemical coding.

We investigate stimulus specificity of repetition priming in a tractable model system; the feeding network of Aplysia. Previous studies primarily focused on an aspect of behavior that is altered during ingestive priming, radula opening. Priming of radula opening occurs when two modulatory peptides [feeding circuit activating peptide (FCAP) and cerebral peptide-2 (CP-2)] are released from the cholinergic command-like neuron cerebral buccal interneuron 2. Effects of FCAP/CP-2 on radula opening motor neurons are cAMP mediated. The present experiments sought to determine whether FCAP/CP-2 and cAMP are also involved in the priming of radula opening during an incompatible activity, i.e., during egestive motor programs. Egestive priming is induced when motor programs are triggered by afferents with processes in the esophageal nerve. We demonstrate that egestive priming is not FCAP/CP-2 mediated. Instead, it is induced by an unrelated peptide (small cardioactive peptide), which exerts PKC-mediated effects. Our data, therefore, suggest that different feeding motor programs are primed via actions of different sets of intercellular and intracellular substances. We suggest that this accounts for the stimulus specificity that can be characteristic of repetition priming. Different stimuli activate different central pattern generator inputs. These inputs release different modulators, which induce functionally distinct motor programs.

PKC-mediated GABAergic enhancement of dopaminergic responses: implication for short-term potentiation at a dual-transmitter synapse

Transmitter-mediated homosynaptic potentiation is generally implemented by the same transmitter that mediates the excitatory postsynaptic potentials (EPSPs), e.g., glutamate. When a presynaptic neuron contains more than one transmitter, however, potentiation can in principle be implemented by a transmitter different from that which elicits the EPSPs. Neuron B20 in Aplysia contains both dopamine and GABA. Although only dopamine acts as the fast excitatory transmitter at the B20-to-B8 synapse, GABA increases the size of these dopaminergic EPSPs. We now provide evidence that repeated stimulation of B20 potentiates B20-evoked dopaminergic EPSPs in B8 apparently via a postsynaptic mechanism, and short-term potentiation of this synapse is critical for the establishment and maintenance of an egestive network state. We show that GABA can act postsynaptically to increase dopamine currents that are elicited by direct applications of dopamine to B8 and that dopamine is acting on a 5-HT3-like receptor. This potentiation is mediated by GABAB-like receptors as GABAB-receptor agonists and antagonists, respectively, mimicked and blocked the potentiating actions of GABA. The postsynaptic actions of GABA rely on a G protein-mediated activation of PKC. Our results suggest that the postsynaptic action of cotransmitter-mediated potentiation may contribute to the maintenance of the egestive state of Aplysia feeding network and, in more general terms, may participate in the plasticity of networks that mediate complex behaviors.

Motor Outputs in a Multitasking Network: Relative Contributions of Inputs and Experience-Dependent Network States

Network outputs elicited by a specific stimulus may differ radically depending on the momentary network state. One class of networks states-experience-dependent states-is known to operate in numerous networks, yet the fundamental question concerning the relative role that inputs and states play in determining the network outputs remains to be investigated in a behaviorally relevant manner. Because previous work indicated that in the isolated nervous system the motor outputs of the Aplysia feeding network are affected by experience-dependent states, we sought to establish the behavioral relevance of these outputs. We analyzed the phasing of firing of radula opening motoneurons (B44 and B48) relative to other previously characterized motoneurons. We found that the overall pattern of motoneuronal firing corresponds to the phasing of movements during feeding behavior, thus indicating a behavioral relevance of network outputs. Previous studies suggested that network inputs act to trigger a response rather than to shape its characteristics, with the latter function being fulfilled by network states. We show this is an oversimplification. In a rested state, different inputs elicited distinct responses, indicating that inputs not only trigger but also shape the responses. However, depending on the combination of inputs and states, responses were either dramatically altered by the network state or were indistinguishable from those observed in the rested state. We suggest that the relative contributions of inputs and states are dynamically regulated and, rather than being fixed, depend on the specifics of states and inputs.

A memoryless, stochastic mechanism of timing of phases of behavior by a neural network controller

AbstractFor a sensorimotor network to generate adaptive behavior in the environment, the phases of the behavior must be appropriately timed. When the behavior is driven simply by the sensory stimuli from the environment, these can supply the timing. But when the behavior is driven by an internal "goal" that ignores and perhaps even opposes the immediate sensory stimuli, the timing must be generated internally by the network. We have modeled a realistic behavioral scenario that requires such internal timing.When the sea slug Aplysia feeds, it incrementally ingests long strips of seaweed, driven by ingestive stimuli emanating from the seaweed. But if, having ingested a strip, the animal fails to break the strip off the substrate, it must incrementally egest the entire strip again. To do this, it must ignore the inherent ingestiveness of the seaweed and generate the opposite, egestive behavior, driven by an internal egestive goal, for a length of time that is appropriate for the length of the strip to be egested.In previous work, we found that a differential-equation model of the Aplysia feeding network, with dynamics like those experimentally observed, performed this task extremely well. In this model, the goal-driven egestion was appropriately timed by a slowly decaying dynamical transient that "remembered" the time elapsed since the beginning of the egestion.We have now used genetic algorithms to evolve very simple artificial neural network controllers that perform the task equally well. But these networks time the egestion by a completely different mechanism. Their dynamics are characterized by discrete ingestive and egestive attractors, to which they switch in response to ingestive and egestive stimuli. However, the switch in behavior follows the switch in stimulus only with a considerable delay, during which the network continues to generate the old behavior. Existing always near an attractor, the network has no long-term memory. Instead, the switch in behavior finally occurs when a sufficiently high local stimulus density appears in the stochastic stimulus input stream. This complex event occurs rarely. To perform the task, the evolution of the network tunes its connection weights so that the switch requires a density that occurs, on average, about as often as the time that is required to egest the typical length of seaweed strip with which the network is evolved. Thus a simple memoryless network, aware of only the local stimulus, is nevertheless able to organize behavior over arbitrarily long time scales.

Dynamical basis of intentions and expectations in a simple neuronal network.

Selection of behavioral responses to external stimuli is strongly influenced by internal states, such as intentions and expectations. These internal states are often attributed to higher-order brain functions. Yet here we show that even in the simple feeding network of Aplysia, external stimuli do not directly specify which motor output is expressed; instead, the motor output is specified by the state of the network at the moment of stimulation. The history-dependence of this network state manifests itself in the same way as do intentions and expectations in the behavior of higher animals. Remarkably, we find that activity-dependent plasticity of a synapse within the network itself, rather than some higher-order network, mediates one important aspect of the change in the network state. Through this mechanism, changes in the network state become an automatic consequence of the generation of behavior. Altogether, our findings suggest that intentions and expectations may emerge within behavior-generating networks themselves from the plasticity of the very processes that generate the behavior.

Motor control of buccal muscles in Aplysia

Motor control of buccal muscles in Aplysia