Dr. J. David Robertson and his colleagues are investigating the physiological processes underlying learning and memory, using the common octopus as an experimental subject. This animal is an ideal choice for a simple model system, since it has the most highly developed brain of all known invertebrates. It is likely that the basic principles found to operate here will also be applicable to higher (vertebrate) species as well. The basic approach is to study the morphological effects of tactile learning on the octopus brain by the use of electron microscopy (EM), comparing brains of trained and untrained animals. Naive animals are taught a touch learning paradigm, e.g., to accept a grooved and reject a smooth rod. It is assumed that small cellular changes occur with learning, and that these changes can be detected by EM techniques. In particular, Dr. Robertson believes that new synapses are formed with learning, and that the first step in this synapse-formation process is an extension of minute finger-like projections (filopodia) of neurons, resembling those extended by neurons in tissue culture. The extension of growth cone filopodia depends on the polymerization of the protein molecule, actin (rather than upon protein synthesis). The drugs cytochalasin-B and -D can both reversibly interfere with actin polymerization. If Dr. Robertson's theory is correct, these drugs should also cause a reversible loss of learning ability without altering previously established memories. The three main goals of the present project are: 1) to demonstrate that this treatment does indeed cause a reversible block of learning without interfering with previously-established memories, 2) to show that the numbers of filopodia increase during learning and decrease during periods of quiescence, and 3) most importantly, to reveal that the numbers of filopodia are significantly decreased in brains that have been injected with the cytochalasin drugs. Ultimatedly Dr. Robertson will attempt experiments with other drugs, such as nerve growth factors (that are known to promote filopodial extension in growth cones), and be able to show that this treatment increases learning ability. The general principles discovered should help in understanding ways to improve learning and memory ability in humans, and perhaps have implications for the alleviation of memory impairments such as those seen in afflictions such as Alzheimer's disease.
