Synaptic Plasticity as a CAS

There are many genetic markers which help guide the brainıs wiring during its initial development and activity. Chemical gradients guide growing axons to their targets. During the early period of life, sufficient currents or potentials across a synapse cause the post-synaptic neuron to release a retrograde neurotransmitter. This neurotransmitter usually consists of a neurotrophin (such as Nerve Growth Factor, NGF). These neurotrophin helps the pre-synaptic neuron grow and also during the initial development, neurotrophins can prevent apoptosis (preprogrammed cell suicide). Thus, the neurons that are used frequently receive neurotrophins and grow and survive while those that do not receive sufficient stimulation die off. However, after maturation, an animal can continue to learn new skills, acquire memories, and continue to develop. These changes occur through changes in the synapses that therefore change the brainıs wiring. The strengthening or weakening of a synapse based on experience/input is known as synaptic plasticity.

Rules
The basic rules neurons use to process information consist of input/output rules on firing. If a neurotransmitter activates enough receptors to let in a minimum amount of calcium and sodium ions, then a depolarization will occur in the membrane. A strong enough depolarization or a combination of weaker ones will reach a threshold and trigger an excitatory post-synaptic potential (EPSP). This is equivalent to a ³fire rule² where if the neuron receives so much stimulation fire, if receives less then do not fire. Synaptic plasticity refers the ability of a synapse to change its baseline at what it defines as the threshold to fire or not. Thus, the neurons involved can become more or less sensitive to signals coming through.

Meta-Rules
The two mechanisms for synaptic plasticity thus discovered by neuroscientists are long-term potentiation (LTP) and long-term depression (LTD). LTP refers to a process where a brief but rapid series of intense stimulation causes a synapse to be more responsive to future stimuli. Long-term depression is a process where low frequency stimulation causes the synapse to become less responsive to future stimulation. Thus, a rapid series of excitatory responses changes the rules of the synapse. Instead of firing if stimulation reaches a baseline of Ĝm , the post-synaptic neuron will now fire if excited by a lower threshold of Ĝm1. This process allows the brain to rewire its connections. A pathway that is intensely activated induces LTP which focuses more attention to that stimulation by increasing the sensitivity of the synapses. LTP is believed to play a part in memory and organization of the visual cortex. A hypothetical role of LTP in memory is that a new memory is formed by sensory information and emotion that strongly excites a certain pathway in the brain. With LTP, the synapses in that pathway are now more sensitive to future stimuli. Thus, if one part of the memory is activated by some sensory experience, then that normal stimulation can activate the entire pathway and all aspects of the memory can be recalled. LTP is also seen in the formation of ocular dominance in the primary visual cortex. Competing visual information from the left and right eyes strengthens their connections through the primary visual cortex (also known as V1). A balance of information prevents encroachment by one or the other eye, and equal width ocular dominant columns appear. However, if monocular deprivation occurs early during life (where one eye receives no visual information), then the other eye can take over all the space in V1. It strengthens its synapses through the visual stimulation it receives while the deprived eye has no activation and its connections are weakened. The rules/meta-rules aspect of synaptic plasticity allows the brain to carry out complex processes that occur post-development.

Meta-meta-rules
In the case of ocular dominance, an even higher order of rules can be seen to take affect. With the development of ocular dominance (or the takeover of visual cortex by one eye) can only occur during a short period of time early in life known as the critical period. During the critical period, LTP and LTD are easily induced in the brain. They allow ocular dominant columns to develop in normal mammals. However, after the critical period, LTP and LTD can no longer significantly be established. Thus, for an animal that has had monocular deprivation during the critical period, no amount of normal, binocular vision afterwards will restore normal visual processing with ocular dominant columns. Likewise, an animal with vision in both eyes during the critical period will have ocular dominance in V1 and monocular deprivation will not change that significantly. Thus as LTP and LTD function as meta-rules changing the synapses normal rules on when to fire based on what stimulation, there is a set of meta-meta-rules that govern when LTP and LTD can occur. LTP takes place through a complex set of molecular reactions. Predominantly theories hold that there are age-dependent enzymes in this process. Through activity, these molecules interact with others in a chain reaction which eventually turns off the genes for their expression. This activity-dependent nature of the critical period can be seen in experiments where dark-rearing animals extends the critical period.

Mechanisms of LTP
The rules and meta-rules governing the firing of neurons represents an analytical, computational aspect of the brainıs processing that is related to complex adaptive systems. However, it is a relevant point to understand how the brain carries out these functions biologically. From the extensive research on synaptic plasticity in regards to ocular dominance there has emerged an elegant, complex, and widely-held theory of how LTP actually occurs in neurons and synapses. This theory is centered around the role of NMDA (N-methyl-D-aspartate) receptors in the post-synaptic membrane. A neurotransmitter used in visual cortex neurons is glutamate, and it can activate both NMDA receptors and also non-NMDA receptors. For the non-NMDA receptors, glutamate is excitatory and allows Na+ to enter the post-synaptic membrane and depolarize it. Glutamate will not excite or inhibit the post-synaptic membrane when it attaches to NMDA receptors except after rapid impulses. The reason for this is that the NMDA receptors have a magnesium ion blocking their channel. However, if enough non-NMDA receptors are activated repeatedly over a short duration, the post-synaptic membrane becomes sufficiently depolarized to repel the Mg+ ion from the NMDA receptor. Now, if glutamate comes into contact with the NMDA receptor proteins, it activates them and they allow Na+ and Ca2+ to enter the cell. Thus, when glutamate is able to massively stimulate the non-NMDA receptors, it then can stimulate the surrounding NMDA receptors as well and let calcium ions into the cell. Certain enzymes such as kinases are activated by specific ion concentrations; some of the specific ion concentration requirements are met when the Ca2+ ions enter the cell through the NMDA receptors. These proteins in turn maintain the receptor proteins in the membrane. There is another level interaction where some of the receptors stimulated are also attached to G-proteins on the interior of the cell. The G-proteins are thus activated and stimulate second-messengers such as cyclic AMP which can regulate gene expression. By selectively and temporally turning on genes, these molecules can change the receptor population.

Evolutionary aspects of synapse plasticity
The only characteristic usually associated with complex adaptive systems that is not completely evident in the process of synaptic plasticity regards the evolutionary nature of most CAS's. There is some evidence for evolutionary processes in synaptic plasticity. During early life, activity of synapses releases neurotrophins which insure cell survival. In this process, synaptic plasticity increases neurotrophins for neurons with LTP and thus a selection process is made. Even after development, one can argue that an autonomous force is selecting for the neurons. Neurons with LTP from high frequency stimulation have stronger synapses, and one could argue that they are more fit. In fact, in this sense LTP and LTD can be seen as the autonomous forces carrying out the evolutionary changes, where active synapses become stronger and inactive synapses become weaker. However, there is a danger here of tautology. Whereas survival of the fittest has the questions of how do decide the criteria (those who survive are labeled the fittest, and the fittest are the ones who survive), the same questions arise in labeling the fitness of the synapses based on strength and activity. However, the greatest lack of evolutionary characteristics in synaptic plasticity involves not adaptation nor selection but reproduction. The selection of which neurons survive (during brain development) or grow stronger does not translate into sexual recombination and reproduction which a key factor in the evolutionary process. In this light, it appears that the changes involved in synaptic plasticity are adaptive but do not have an evolutionary growth.