10 Unsolved Science Mysteries (part 4) : How Does the Brain Think and Form Memories?

     The brain is a chemical computer. Interactions between the neurons that form its circuitry are mediated by molecules: specifically, neurotransmitters that pass across the synapses, the contact points where one neural cell wires up to another.
      This chemistry of the mind is perhaps at its most impressive in the operation of memory, in which abstract principles and concepts—a telephone number, say, or an emotional association—are imprinted in states of the neural network by sustained chemical signals. How does chemistry create a memory that is both persistent and dynamic, as well as able to recall, revise and forget?
    We now know parts of the answer. A cascade of biochemical processes, leading to a change in the amounts of neurotransmitter molecules in the synapse, triggers learning for habitual reflexes. But even this simple aspect of learning has shortand long-term stages. Meanwhile more complex so-called declarative memory (of people, places, and so on) has a different mechanism and location in the brain, involving the activation of a protein called the NMDA receptor on certain neurons.
    Blocking this receptor with drugs prevents the retention of many types of declarative memory. Our everyday declarative memories are often encoded through a process called long-term potentiation, which involves NMDA receptors and is accompanied by an enlargement of the neuronal region that forms a synapse. As the synapse grows, so does the “strength” of its connection with neighbors—the voltage induced
at the synaptic junction by arriving nerve impulses. 

      The biochemistry of this process has been clarified in the past several years. It involves the formation of
filaments within the neuron made from the protein actin—part of the basic scaffolding of the cell and the material that determines its size and shape. But that process can be undone during a short period before the change is consolidated if biochemical agents prevent the newly formed filaments from stabilizing.
      Once encoded, long-term memory for both simple and complex learning is actively maintained by switching on genes that give rise to particular proteins. It now appears that this process can involve a type of molecule called a prion. Prions are proteins that can switch between two different conformations. One of the conformations is soluble, whereas the other is insoluble and acts as a catalyst to switch other molecules like it to the insoluble state, leading these molecules to aggregate. Prions were first discovered for their role in neurodegenerative conditions such as mad cow disease, but prion mechanisms have now been found to have beneficial functions, too: the formation of a prion aggregate marks a particular synapse to retain a memory.
     There are still big gaps in the story of how memory works, many of which await  filling with the chemical details. How, for example, is memory recalled once it has been stored? “This is a deep problem whose analysis is just beginning,” says neuroscientist and Nobel laureate Eric Kandel of Columbia University. Coming to grips with the chemistry of memory offers the enticing and controversial prospect of pharmacological enhancement.
     Some memory-boosting substances are already known, including sex hormones and synthetic chemicals that  act on receptors for nicotine, glutamate, serotonin and other neurotransmitters. In fact, according to neurobiologist Gary Lynch of the University of California, Irvine, the complex sequence of steps leading to long-term learning and memory means that there are many potential targets for such memory drugs.

SOURCE : SCIENTIFIC AMERICAN OCTOBER 2011