UNIT 4: LEARNING AND MEMORY. MOLECULAR MECHANISMS.
1. THE NATURE OF LEARNING.
Learning comprises all the processes by which experiences modify our nervous system and our behavior. Experiences aren’t
stored, they indeed change the manner we perceive, perform, think and plan. They do so by changing physically the structure of
the nervous system, modifying the neural circuits that participate in perception, thought, planning and action.
According with Hebb the weight between two neurons increases if the two neurons activate simultaneously and reduces if they
activate separately. And engrams are neuronal nets or neuronal networks.
2. EFFECTS OF EXPERIENCE IN THE STRUCTURE OF THE NERVOUS SYSTEM.
Formal training and informal experience produce neurochemical and anatomical changes in the brain.
Enriched vs. impoverished condition produces: increases in the cholinergic activity, increases in the weight of the cortex and
increases in the thickness of the cortex.
Informal experience promotes dendritic growth in the cerebral cortex. Increases in the number of dendritic branches, increases in
the size of the existing synapses and increases in the average length of the postsynaptic thickness.
Training produces new synaptic conexions. Neurons morphology changes continuously through life. The electric activity induces
increases in the number of dendritic branches and spines, and the formation of new synapses. Training correlates with increases in
the expression of different genes. Training induces the survival of new neurons in the hippocampus.
Neurogenesis occurs in the Olfactory bulbs and the Dentate gyrus of the adult brain. Rats maintained in enriched environments
have more neurogenesis. The new neurons incorporate to local circuits. The survival of the new neurons is associated to some
hippocampus-dependent types of learning.
Memory consolidation requires protein synthesis:
•Potassium chloride: inhibits the access of ions Ca++, blocks the formation of short-term memory.
•Ouabain: inhibits the Na+-K+ ATPasa blocks the formation of medium-term memory.
•Anisomycin: antibiotic that inhibits protein synthesis, block only the formation of long-term memory.
3. NEURAL MECHANISMS OF LEARNING AND MEMORY.
3.1. MECHANISMS OF SYNAPTIC PLASTICITY AND LEARNING IN INVERTEBRATES.
3.1.1. Aplysia californica.
The gill-withdrawal reflex of Aplysia californica is one of the most productive models, in terms of number and quality of data, for
our knowledge on the neurobiological mechanisms of learning and memory.
•Habituation: if a soft jet of water is squirted onto the siphon of the Aplysia, the gill will retract, but with repeated
presentations the retraction gradually attenuates. Habituation of the gill-withdrawal reflex in Aplysia requires only two
neurons. The habituation of the gill-withdrawal reflex is associated with a pre-synaptic. Repeated stimulation of a
sensory neuron causes the gradual decrease of the excitatory post-synaptic potential in a motor neuron (L7). This change
is caused by a decrease in the amount of transmitter released to the synaptic cleft, caused by a decrease in the entry of Ca
++ in the axon terminal of the sensory neuron.
•Dishabituation: if a brief and very mild electric shock is administered to the head or tail of the Aplysia previously
habituated, it results in the recovery of the pretraining gill-withdrawal in response to the stimulus in the siphon.
•Sensitization: if a brief and mild electric shock is administered to the head of the Aplysia previously habituated, it results
in a exaggerated gill-withdrawal in response to the stimulus in the siphon. Sensitization also can be produced by the
administration of an aversive IC of median to high intensity. Sensitization of the gill-withdrawal reflex in Aplysia
requires three neurons and an axo-axonic synapse. Involves also the stimulation of an interneuron (L29), which makes an
axo-axonic synapse with the sensory neuron. Short-term sensitization of the gill-withdrawal reflex is caused by
presynaptic facilitation in the axo-axonic synapse. Serotonin promotes the synthesis of cAMP, which activates the Kinase
A protein and thus the closure of K+ channels. In consequence, the voltage-gated Ca++ channels remain opened for a
longer time, leading to an increase in glutamate release. Short-term sensitization of the gill-withdrawal reflex depends on
presynaptic facilitation. The longer the voltage-gated Ca++ channels remain opened, more Ca++ enters in the axon
terminal, and more quanta of glutamate are released in the synaptic cleft.
•Classical conditioning: gill-withdrawal in response to a conditioned stimulus, which before training was ineffective to
produce that response. Classical conditioning in Aplysia requires a facilitation dependent on the activity of pre- and post-
synaptic neurons in the axo-axonic synapse. Adenylyl cyclase operates as a detector of the CS-US coincidence.
•Learning: the presynaptic Ca++ coincides with the activation of the Adenylyl cyclase by the G-protein. In
presence of Ca++, the Adenylyl cyclase activated by the G-protein simulates the synthesis of large amounts of
cAMP. Classical conditioning in Aplysia depends on the prolonged depolarization of the presynaptic terminal.
•Memory: cAMP activates PKA which maintains the K+ channels phosphorylated, maintaining enhanced the
release of glutamate. The formation of memories of different duration is based on sequential neurochemical
processes. Phosphorylation of the membrane proteins explains short-term memory, but it is not sufficient for the
formation of long-term memory. There are alternative mechanisms, the permanent activation of Kinase proteins
and protein synthesis. Long-term memory of sensitization, and classical conditioning require gene expression.
With training, PKA activated by cAMP, activates CREB. The increment of CREB increases the synthesis of
