Molluscan Nervous Systems


Neural circuits underlying reflex and rhythmic behaviours in molluscs can be understood at the level of single identified neurons. Using these systems, the most important advances have been made in the understanding of the cellular and molecular basis of learning and memory.

Keywords: molluscs; nervous systems; neurons; behaviour; learning

Figure 1.

Ganglia and neurons of the molluscan CNS. (a) Central ganglia of Aplysia, Lymnaea, Helix and Octopus. Green, buccal ganglia; yellow, cerebral ganglia; pink, pleural ganglia; blue, pedal ganglia; red, abdominal ganglion/viscero‐parietal complex; purple, lobes of the Octopus brain that are involved in visual learning; light brown, lobes of the Octopus brain that are involved in tactile learning. (b) The central ganglia in snails are concentrated around the oesophagus (gut) in the anterior part (‘head’) of the animal's body. (c) Some of the best‐known identified neurons in the abdominal ganglion of Aplysia. L7, gill and siphon motor neuron; yellow, sensory neurons; green, R18 interneuron; purple, other neurons of particular interest. (d) Some of the best‐known identified neurons in the buccal ganglia in the Lymnaea feeding system. The ganglia are shown with the right buccal ganglion twisted to expose the ventral side. B4, B7, B10, motor neurons; black, N1–3 CPG interneurons (d, dorsal; v, ventral; M, medial; L, lateral; t, tonic; p, phasic); green, SO modulatory interneuron. Insert shows an N2v type CPG interneuron filled with carboxyfluorescein.

Figure 2.

Molluscan neural circuits underlying reflexes and rhythmic motor behaviour. (a) Simplified diagram of the overlapping neural networks involved in the defensive inking and gill‐withdrawal reflexes of Aplysia. Yellow box, sensory neurons (SNs); green circles, modulatory interneurons; boxes with red or blue outline, motor neurons (MNs) for inking and gill‐withdrawal, respectively. Solid lines, monosynaptic connections; dashed line, polysynaptic connection. Vertical bars, chemical excitatory synapses; horizontal bar, peripheral sensory endings. (b) The more complex neuronal network underlying rhythmic feeding behaviour in Lymnaea. The degree of simplification is the same as for the Aplysia gill withdrawal/inking circuitry. Yellow box, sensory neurons; green circles, modulatory interneurons; circles and boxes with red, blue or green outline, CPG interneurons and motor neurons active in the three different phases of feeding (protraction, rasp, swallow). Filled circles, chemical inhibitory synapses; vertical bars, chemical excitatory synapses; horizontal bar, peripheral sensory endings; zigzag lines, electrotonic connections.

Figure 3.

Cellular models of classical conditioning in molluscs. (a) In vitro analogue of differential aversive classical conditioning in Aplysia. Conditioning consists of pairing spike activity in a sensory neuron (SN1) with a shock to the tail (aversive training) in reduced preparations. Spike activity in another SN (SN2) was explicitly unpaired in the same preparations. After training, the spikes evoked in the paired SNs are longer in duration and evoke larger EPSPs in motor neurons compared to spikes triggered in unpaired SNs (cellular correlate). The simplified cellular mechanism (model) is based on activity‐dependent amplification of heterosynaptic facilitation of the sensory to motor neuron excitatory chemical synapse (large black triangle) by inputs from a facilitator modulatory neuron activated by tail shock. (b) Appetitive classical conditioning in intact Lymnaea followed by an electrophysiological analysis of the memory trace in a reduced preparation. Touch to the lip was paired with application of sucrose, a food stimulus (appetitive training). After training, touch to the lip evokes more fictive feeding cycles (indicated by dots at the beginning of each cycle) on the B3 motor neurons in preparations made from animals that received paired stimuli compared to those that received unpaired stimuli (cellular correlate). The circuit (model) is based on the observation that cellular traces of learning were recorded at several sites in the brain and indicate that there might be multiple sites of plasticity (large black triangle) in this more complex system. Small black triangles are nonfacilitating synaptic inputs.

Figure 4.

A comparison of the main presynaptic molecular events underlying short‐ and long‐term memory formation during sensitization in Aplysia. Serotonin (5‐hydroxytryptamines, 5‐HT), released from facilitator interneurons activated by tail shock, activates AC, which in turn leads to the elevation of cAMP levels in the sensory neuron terminal presynaptic to the motor neuron. A cAMP‐activated protein kinase enzyme (protein kinase A, PKA) phosphorylates a K+ channel, which closes, and this leads to action potential broadening and, consequently, to increased Ca2+ influx, resulting in increased transmitter release. Repeated tail shocks or repeated applications of 5‐HT cause a greater elevation of cAMP levels and this results in the translocation of PKA and MAPK into the nucleus. Here, through the activation of the transcription factor CREB protein, a cascade of early‐immediate and late genes are activated and this leads to the production of a persistently active PKA and long‐term changes in neuronal morphology underlying long‐term memory formation. Adapted and reproduced from Figure 7 of Milner et al. with permission from Cell Press.

Figure 5.

Interacting pre‐ and postsynaptic mechanisms contributing to classical conditioning in Aplysia. Paired CS‐US stimulation activates postsynaptic NMDA receptors due to the coincidental presynaptic activation and resulting release of glutamate (Glu) and postsynaptic depolarization by US‐activated excitatory interneurons (Int). The US, through the activation of the serotonergic (5‐HT) facilitatory interneurons, also probably activates phospholipase C (PLC) in the motor neuron via a G protein‐coupled 5‐HT receptor, which in turn contributes to inositol‐1,4,5‐triphosphate (IP3) mediated Ca2+ release from internal Ca2+ stores. This, together with the Ca2+ influx through the activated NMDA receptors leads to protein kinase C (PKC) mediated upregulation of AMPA receptor function and stimulation of a retrograde signal. The former increases postsynaptic sensitivity to Glu, while the latter triggers the persistent presynaptic cellular changes that accompany classical conditioning, possibly through the transsynaptic activation of PKA in the sensory neuron. This model, which is based on work in the Glanzman laboratory, only indicates an indirect persistent effect of the 5‐HT‐ergic facilitatory interneurons on the sensory neurons, but this notion is still controversial (see Antonov et al., ). Adapted and reproduced from Figure of Roberts and Glanzman with permission from Elsevier).



Angers A, Fioravante D and Chin J et al. (2002) Serotonin stimulates phosphorylation of Aplysia synapsin and alters its subcellular distribution in sensory neurons. Journal of Neuroscience 22: 5412–5422.

Antonov I, Antonova I, Kandel ER and Hawkins RD (2003) Activity‐dependent presynaptic facilitation and Hebbian LTP are both required and interact during classical conditioning in Aplysia. Neuron 37: 135–147.

Benjamin PR and Elliott CJH (1989) Snail feeding oscillator: the central pattern generator and its control by modulatory interneurons. In: Jacklet J (ed.) Neuronal and Cellular Oscillators New York: Marcel Dekker.

Benjamin PR, Staras K and Kemenes G (2000) A systems approach to the cellular analysis of associative learning in the pond snail Lymnaea. Learning and Memory 7: 124–131.

Brembs B (2003) Operant conditioning in invertebrates. Current Opinion in Neurobiology 13: 710–717.

Brierley MJ, Yeoman MS and Benjamin PR (1997) Glutamatergic N2v cells are central pattern generator interneurons of the Lymnaea feeding system: a new model for rhythm generation. Journal of Neurophysiology 78: 3396–3407.

Byrne JH (1982) Cellular and biophysical mechanisms contributing to regulation of reflex excitability of inking behavior in Aplysia. Federation Proceedings 41: 2147–2152.

Carew TJ and Sahley CL (1986) Invertebrate learning and memory: from behavior to molecules. Annual Review of Neuroscience 9: 435–487.

Fiorito G and Scotto P (1992) Observational learning in Octopus vulgaris. Science 256: 545–547.

Hanlon RT and Messenger JB (1996) Cephalopod Behaviour. Cambridge, UK: Cambridge University Press.

Hawkins RD, Abrams TW, Carew TJ and Kandel ER (1983) A cellular mechanism of classical conditioning in Aplysia: activity‐dependent amplification of presynaptic facilitation. Science 219: 400–405.

Hochner B, Brown ER, Langella M, Shomrat T and Fiorito G (2003) A learning and memory area in the octopus brain manifests a vertebrate‐like long‐term potentiation. Journal of Neurophysiology 90: 3547–3554.

Jones NG, Kemenes I, Kemenes G and Benjamin PR (2003) A persistent cellular change in a single modulatory neuron contributes to associative long‐term memory. Current Biology 13: 1064–1069.

Kandel ER (1976) Cellular Basis of Behavior: An Introduction to Behavioral Neurobiology. San Francisco: WH Freeman.

Kemenes G and Benjamin PR (1989) Appetitive learning in snails shows characteristics of conditioning in vertebrates. Brain Research 489: 163–166.

Kemenes G, Staras K and Benjamin PR (1997) In vitro appetitive classical conditioning of the feeding response in the pond snail Lymnaea stagnalis. Journal of Neurophysiology 78: 2351–2362.

Kemenes I, Kemenes G, Andrew RJ, Benjamin PR and O'Shea M (2002) Critical time‐window for NO‐cGMP dependent long‐term memory formation after one‐trial appetitive conditioning. Journal of Neuroscience 22: 1414–1425.

Milner B, Squire LR and Kandel ER (1998) Cognitive neuroscience and the study of memory. Neuron 20: 445–468.

Ribeiro MJ, Serfõzõ Z and Papp A et al. (2003) Cyclic AMP response element binding (CREB)‐like proteins in a molluscan brain: cellular localisation and learning‐induced phosphorylation. European Journal of Neuroscience 18: 1223–1234.

Roberts AC and Glanzman DL (2003) Learning in Aplysia: looking at synaptic plasticity from both sides. Trends in Neuroscience 26(12): 662–670.

Robertson JD (1994) Cytochalasin D blocks touch learning in Octopus vulgaris. Proceedings of the Royal Society of London B 258: 61–66.

Robertson JD, Bonaventura J and Kohn AP (1994) Nitric oxide is required for tactile learning in Octopus vulgaris. Proceedings of the Royal Society of London B 256: 269–273.

Staras K, Kemenes G and Benjamin PR (1998) Pattern‐generating role for motoneurons in a rhythmically active neuronal network. Journal of Neuroscience 18: 3669–3688.

Staras K, Kemenes G and Benjamin PR (1999) Cellular traces of behavioral classical conditioning can be recorded at several specific sites in a simple nervous system. Journal of Neuroscience 19: 347–357.

Staras K, Kemenes I, Benjamin PR and Kemenes G (2003) Loss of self‐inhibition is a cellular mechanism for episodic rhythmic behaviour. Current Biology 13: 116–124.

Straub VA, Staras K, Kemenes G and Benjamin PR (2002) Endogenous and network properties of Lymnaea feeding central pattern generator interneurons. Journal of Neurophysiology 88: 1569–1583.

Wells MJ (1978) Octopus. Physiology and Behavior of an Advanced Invertebrate. London: Chapman and Hall.

Further Reading

Bullock TH and Horridge GA (1965) Structure and Function in the Nervous Systems of Invertebrates. San Francisco: WH Freeman.

Byrne JH (1987) Cellular analysis of associative learning. Physiological Reviews 67: 329–439.

Glanzman DL (1995) The cellular basis of classical conditioning in Aplysia californica – it's less simple than you think. Trends in Neuroscience 18: 30–36.

Kandel ER (1979) Behavioral Biology of Aplysia. San Francisco: WH Freeman.

Krasne FB and Glanzman DL (1995) What we can learn from invertebrate learning. Annual Review of Psychology 46: 585–624.

Squire LR and Kandel ER (1999) Memory. From Mind to Molecules. New York: Scientific American Library.

Wilbur KM (ed. in chief) and Willows AOD (ed.) (1985, 1986) The Mollusca, vols 8 and 9, Neurobiology and Behavior, parts 1 and 2. Orlando, FL: Academic Press.

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Benjamin, Paul R, Kemenes, György, and Staras, Kevin(Sep 2005) Molluscan Nervous Systems. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0004073]