Multiple changes in connectivity between buccal ganglia mechanoafferents and motor neurons with different functions after learning that food is inedible in .

Changes caused by learning that a food is inedible in were examined for fast and slow synaptic connections from the buccal ganglia S1 cluster of mechanoafferents to five followers, in response to repeated stimulus trains. Learning affected only fast connections. For these, unique patterns of change were present in each follower, indicating that learning differentially affects the different branches of the mechanoafferents to their followers.

Repeated stimulation of feeding mechanoafferents in generates responses consistent with the release of food.

How does repeated stimulation of mechanoafferents affect feeding motor neurons? Monosynaptic connections from a mechanoafferent population in the buccal ganglia to five motor followers with different functions were examined during repeated stimulus trains. The mechanoafferents produced both fast and slow synaptic outputs, which could be excitatory or inhibitory. In contrast, other mechanoafferents produce only fast excitation on their followers.

An in vitro analog of learning that food is inedible in : decreased responses to a transmitter signaling food after pairing with transmitters signaling failed swallowing.

An in vitro analog of learning that a food is inedible provided insight into mechanisms underlying the learning. learn to stop responding to a food when they attempt but fail to swallow it. Pairing a cholinergic agonist with an NO donor or histamine in the cerebral ganglion produced significant decreases in fictive feeding in response to the cholinergic agonist alone.

Identification of an allatostatin C signaling system in mollusc Aplysia.

Neuropeptides, as pervasive intercellular signaling molecules in the CNS, modulate a variety of behavioral systems in both protostomes and deuterostomes. Allatostatins are neuropeptides in arthropods that inhibit the biosynthesis of juvenile hormones. Based on amino acid sequences, they are divided into three different types in arthropods: allatostatin A, allatostatin B, allatostatin C.

Nitric oxide and l-arginine have mixed effects on mammalian feeding in condition of a high motivation to feed.

Feeding inhibition caused by satiation in rats is partially mediated by the unconventional neurotransmitter nitric oxide (NO). Thus, in satiated rats blocking NO production increases feeding, and treatment with the NO precursor l-arginine or with an NO donor reduces feeding beyond that caused by satiation. Do NO and l-arginine also inhibit feeding when feeding motivation is high? When feeding motivation in satiated animals was hedonically increased by offering a highly attractive food, blocking NO production reduced the quantity eaten, rather than increasing it, indicating that hedonic aspects of food are partially mediated by NO.

Multiple Local Synaptic Modifications at Specific Sensorimotor Connections after Learning Are Associated with Behavioral Adaptations That Are Components of a Global Response Change.

Learning causes local changes in synaptic connectivity and coordinated, global changes affecting many aspects of behavior. How do local synaptic changes produce global behavioral changes? In the hermaphroditic mollusc , after learning that food is inedible, memory is expressed as bias to reject a food and to reduce responses to that food. We now show that memory is also expressed as an increased bias to reject even a nonfood object.

Successful and unsuccessful attempts to swallow in a reduced preparation regulate feeding responses and produce memory at different neural sites.

Sensory feedback shapes ongoing behavior and may produce learning and memory. Motor responses to edible or inedible food in a reduced preparation were examined to test how sensory feedback affects behavior and memory. Feeding patterns were initiated by applying a cholinomimetic onto the cerebral ganglion.

Nitric oxide and l-arginine regulate feeding in satiated rats.

Nitric Oxide (NO) and its precursor l-arginine were found to inhibit feeding in rats with a low motivation to eat, as they do in Aplysia. In rats that are relatively satiated, treatment with an NO blocker increased feeding, and treatment with an NO donor or with either of 2 doses of l-arginine inhibited feeding. NO and l-arginine modulated several parameters of feeding, such as the total duration of appetitive behaviors, the time spent feeding, the quantity of food eaten and the number of feeding bouts.

NO is required for memory formation and expression of memory, and for minor behavioral changes during training with inedible food in .

A learning experience may lead to changes in behavior during the experience, and also to memory expressed at a later time. Are signals causing changes in behavior during the learning experience related to the formation and expression of memory? We examined this question, using learning that food is inedible in Treatment of an isolated buccal ganglia preparation with an NO donor elicited rejection-like motor programs. Rejection initiated by NO production is consistent with aspects of behavioral changes seen while animals learn, and with memory formation.

Molecular correlates of separate components of training that contribute to long-term memory formation after learning that food is inedible in .

Training with inedible food for a period that is too brief to produce long-term memory becomes effective in producing memory when training is paired with a nitric oxide (NO) donor. Lip stimulation for the same period of time paired with an NO donor is ineffective. Using qPCR, we examined molecular correlates of brief training versus lip stimulation, of treatment with an NO donor versus saline, and of the combined stimuli producing long-term memory.

New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences.

Localization of molecular correlates of memory consolidation to buccal ganglia mechanoafferent neurons after learning that food is inedible in Aplysia.

Training paradigms affecting Aplysia withdrawal reflexes cause changes in gene expression leading to long-term memory formation in primary mechanoafferents that initiate withdrawal. Similar mechanoafferents are also found in the buccal ganglia that control feeding behavior, raising the possibility that these mechanoafferents are a locus of memory formation after a training paradigm affecting feeding. Buccal ganglia mechanoafferent neurons expressed increases in mRNA expression for the transcription factor ApC/EBP, and for the growth factor sensorin-A, within the first 2 h after training with an inedible food.

Variables controlling entry into and exit from the steady-state, one of two modes of feeding in Aplysia.

Background: Aplysia feeding is a model system for examining the neural mechanisms by which changes in motivational state control behavior. When food is intermittently present, Aplysia eat large meals controlled by a balance between food stimuli exciting feeding and gut stimuli inhibiting feeding. However, when food is continuously present animals are in a state in which feeding is relatively inhibited and animals eat little.

Nitric oxide as a regulator of behavior: new ideas from Aplysia feeding.

Nitric oxide (NO) regulates Aplysia feeding by novel mechanisms, suggesting new roles for NO in controlling the behavior of higher animals. In Aplysia, (1) NO helps maintain arousal when produced by neurons responding to attempts to swallow food; (2) NO biases the motor system to reject and reposition food that resists swallowing; (3) if mechanically resistant food is not successfully swallowed, NO mediates the formation and expression of memories of food inedibility; (4) NO production at rest inhibits feeding, countering the effects of food stimuli exciting feeding. At a cellular level, NO-dependent channels contribute to the resting potential of neurons controlling food finding and food consumption.

Autaptic muscarinic self-excitation and nitrergic self-inhibition in neurons initiating Aplysia feeding are revealed when the neurons are cultured in isolation.

Properties of a neuron may arise via endogenous mechanisms, or via interactions with other neurons. Culturing a neuron in isolation is a useful tool to distinguish between endogenous and circuit-derived properties. We identified two remarkable functional features of pattern initiator neurons B31/B32 in Aplysia when these neurons were cultured in isolation.

Neurons controlling Aplysia feeding inhibit themselves by continuous NO production.

Background: Neural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking?

Methodology/principal Findings: Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption.

L-arginine via nitric oxide is an inhibitory feedback modulator of Aplysia feeding.

An increase in L-arginine hemolymph concentration acts as a postingestion signal inhibiting Aplysia feeding. At physiological concentrations (a 10-μM increase over background), the inhibitory effect of L-arginine is too weak to block feeding in hungry animals. However, a 10-μM increase in L-arginine concentration acts along with another inhibitory stimulus, the sustained presence of food odor, to inhibit feeding after a period of access to food.

A brief retraining regulates the persistence and lability of a long-term memory.

An experience extending the persistence of a memory after training Aplysia californica with inedible food also allows a consolidated memory to become sensitive to consolidation blockers. Long-term (24 h) memory is initiated by 5 min of training and is dependent on protein synthesis during the first few hours after training. By contrast, a more persistent (48 h) memory is dependent on a longer training session and on a later round of protein synthesis.

Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible in Aplysia.

Memory that food is inedible in Aplysia arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that NO functions during training as a signal of attempts to swallow.

Autaptic excitation elicits persistent activity and a plateau potential in a neuron of known behavioral function.

Synaptic connections from a neuron onto itself (autapses) are not uncommon, but their contributions to information processing and behavior are not fully understood. Positive feedback mediated by autapses could in principle give rise to persistent activity, a property of some neurons in which a brief stimulus causes a long-lasting response. We have identified an autapse that underlies a plateau potential causing persistent activity in the B31/B32 neurons of Aplysia.

Training with inedible food in Aplysia causes expression of C/EBP in the buccal but not cerebral ganglion.

Training with inedible food in Aplysia increased expression of the transcription factor C/EBP in the buccal ganglia, which primarily have a motor function, but not in the cerebral or pleural ganglia. C/EBP mRNA increased immediately after training, as well as 1-2 h later. The increased expression of C/EBP protein lagged the increase in mRNA.

Currents contributing to decision making in neurons B31/B32 of Aplysia.

Biophysical properties of neurons contributing to the ability of an animal to decide whether or not to respond were examined. B31/B32, two pairs of bilaterally symmetrical Aplysia neurons, are major participants in deciding to initiate a buccal motor program, the neural correlate of a consummatory feeding response. B31/B32 respond to an adequate stimulus after a delay, during which time additional stimuli influence the decision to respond.

Nitric oxide signals that aplysia have attempted to eat, a necessary component of memory formation after learning that food is inedible.

Inhibiting nitric oxide (NO) synthesis during learning that food is inedible in Aplysia blocks subsequent memory formation. To gain insight into the function of NO transmission during learning we tested whether blocking NO synthesis affects aspects of feeding that are expressed both in a nonlearning context and during learning. Inhibiting NO synthesis with L-NAME and blocking guanylyl cyclase with methylene blue decreased the efficacy of ad libitum feeding.