In Search of Memory

In Search of Memory: The Emergence of a New Science of Mind by Eric Kandel, W. W. Norton & Company, 2007. 

Synapse

An early Spanish neuroscientist, Santiago Ramón y Cajal, suggested that memories may be stored in the synapses between nerve cells, rather than within individual cells. The ends of the axons usually have multiple terminals. A terminal is a protrusion that forms a contact (synapse) with a dendrite of the receiving neuron. The terminals release neurotransmitter molecules that travel across the synapse to receptor proteins in the membrane of the dendrite of the receiving neuron.

Aplysia

Kandel chose a sea snail called Aplysia as his experimental animal. At first, he studied neurons that had been removed from Aplysia. Later, he studied a ganglion in the intact animal. In particular, he studied the ganglion involved in the gill withdrawal reflex. 

Short Term and Long Term Memory

There are two different kinds of memory, short term and long term. Short term memory lasts for a few minutes. Long-term memory lasts for days to years. Kandel discovered how short-term memory works at the molecular level. Short-term memory is implemented by an increase the amount and duration of the release of neurotransmitter by an axon terminal. Long-term memory works by building more axon terminals, which requires turning on the genes for the particular proteins used to build the axon terminal. The activator proteins and repressor proteins that regulate this gene expression are themselves regulated by cyclic AMP (adenosine monophosphate) and kinase enzymes.

Messenger RNA

The messenger RNA (mRNA) transcribed from the genes in the neuron’s nucleus goes out to the end of the axon, where ribosomes translate the mRNA into protein. These proteins create new axon terminals and synapses. The cell has an interesting way of controlling whether an mRNA molecule in the axon terminal is translated into protein. The mRNA has a tail of multiple adenine nucleotides called a polyadenine tail. The binding of a regulatory protein molecule to this polyadenine tail converts this mRNA into an active form, which is then translated by the ribosome. This polyadenine tail binding protein is called cytoplasmic polyadenylation element binding protein (CPEB).

Prions and Kausik Si

In 2003 a postdoc in Kandel’s lab named Kausik Si, a graduate of Calcutta University, discovered a new form of CPEB that had a prion-like domain at its N-terminus. Prions are proteins that exist in two different conformation (shapes), and the existence of one protein in a particular conformation can act as a seed crystal, causing neighboring prions to change their conformation to that of the seed prion molecule. The bound CPEB holds the mRNA in the active form, so that the ribosome repeatedly translates the mRNA into axon-terminal proteins. This was the first discovery of a physiological role for a prion.