Aplysia Learning - Molecular Mechanisms

Habituation in the Gill Withdrawal reflex of Aplysia

In Aplysia siphon withdrawal is a protective reflex in response to a touch of siphon skin. Size, strength, and duration of contraction are a function of stimulus intensity.

Non-associative Learning in the Gill Withdrawal reflex

• Habituation: Repeated stimulation of the siphon produces a progressive decrease in siphon withdrawal via a progressively weakening of inputs from the sensory neurons. This effect results from changes at the presynaptic terminal where: (short-term) reduced transmitter release occurs due to inactivation of presynaptic Ca++ channels, (long term) sensory synapes driving the motor neuron are structurally rearranged and reduced in number
• Sensitization: An electric shock preceding a stimulation of the siphon produces an increased response in siphon withdrawal. Bath application of serotonin or injection of cAMP into the motor neuron mimic this effect. This effect is due to changes at the presynaptic terminal with: (short-term) increased transmitter release, (long term) structural rearrangement and an increase in the number of sensory synapes driving the motor neuron. Seretonin is released from facilitating interneurons, and binds to pre-synaptic 5-HT receptors. This activates a G protein, which in turn increases the amount of cyclic AMP by activating Adenylyl cyclase.

In short term changes in synaptic enhancement, the conductance of the votage-gated K-channels is reduced via this cascade, delaying repolarization to rest, broadening the shape of the action potential. and leading to an increased Ca conductance.

During long-term facilitation the same cAMP signalling pathways alter second messenger systems that regulating gene expression and induce protein synthesis. Genes typically consist of a regulatory and a coding region. Transcription of the coding region is regulated by the binding of regulatory proteins to the regulatory region (i.e., the response elements). For example, the cyclic AMP response element (CRE) accepts cyclic AMP response element binding (CREB) proteins. With increased cAMP, PKA is activated and translocated to the nucleus. As CREB proteins are phosphorylated by PKA they bind to the CRE regions of genes. The production of genes leads to long-term changes in synaptic response, structure and number.

Associative Learning in the Gill Withdrawal reflex

Classical Conditioning: An electric tail shock (US) produces gill withdrawal (UR) while a stimulation of the mantel surface alone (NS) does not. However, when tail shock is repeatedly preceded by a stimulation of the mantel surface (CS), the latter is able to acquire a strong gill withdrawal response (CR).

As in sensitization, tail shock triggers release of serotonin from facilitating interneurons and thereby activates presynaptic cAMP via G-protein coupled mechanisms. Activation of the motoneuron is enhanced via the inclusion of NMDA receptors if it is concurrently activated.