Learning

Changes in excitability from learning that act as part of the memory trace do so as primers to initiate further changes in the neurons or by a short term storage mechanism for short term memory. Nonsynaptic plasticity can emerge in during learning as a result of cellular processes, although the timing and persistence is not well understood, nor is the relationship between nonsynaptic plasticity and synaptic output. Studies have shown that nonsynaptic plasticity plays an indirect but important role in the formation of memories. Learning-induced nonsynaptic plasticity is associated with soma depolarization.^[5]

Classical conditioning Evidence of learning-dependent nonsynaptic plasticity in vertebrates

Woody et al^[7] showed that classical conditioning of cat eyeblink reflex is associated with increased excitability and input in the neurons in sensorymotor cortical areas and in facial nucleus. It was observed that increasing excitability from classical conditioning continued after the response stopped. This could indicate that increased excitability functions as a mechanism for memory storage. This was supported by the observation that retraining after suppression of conditioned response produced a much faster rate of learning.^[5]

Experiments of trace conditioning

Experiments have revealed nonsynaptic changes take place during conditional learning. In eyelid conditioning in rabbits, nonsynaptic changes occurred throughout the dorsal hippocampus. This indicates that although excitability changes alone are not enough to explain memory storage processes, nonsynaptic plasticity might be a storage mechanism for phases of memory limited by time. Nonsynaptic changes influence other types of plasticity involved with memory. For example, a nonsynaptic change like depolarization of the resting membrane potential resulting from conditional learning could cause synaptic plasticity in additional conditional learning.^[5]

Nonsynaptic vs synaptic plasticity

Neuroplasticity is the ability of a particular part or region of a neuron to change in strength over time. There are two largely recognized categories of plasticity, synaptic and nonsynaptic. Synaptic plasticity deals directly with the strength of the connection between two neurons, including amount of neurotransmitter released from the presynaptic neuron, and the response generated in the postsynaptic neuron. Nonsynaptic plasticity involves modification of neuronal excitability in the axon, dendritic, and somatic areas of an individual neuron, remote from the synapse.

Synaptic plasticity is the ability of a synapse between two neurons to change in strength over time. Synaptic plasticity is caused by changes in use of the synaptic pathway, namely, the frequency of synaptic potentials and the receptors used to relay chemical signals. Synaptic plasticity plays a large role in learning and memory in the brain. Synaptic plasticity can occur through intrinsic mechanisms, in which changes in synapse strength occur because of its own activity, or through extrinsic mechanisms, in which the changes in synapse strength occur via other neural pathways. Short-term inhibitory synaptic plasticity often occurs because of limited neurotransmitter supply at the synapse, and long term inhibition can occur through decreased receptor expression in the postsynaptic cell. Short term complementary synaptic plasticity often occurs because of residual or increased ion flow in either the presynaptic or postsynaptic terminal , and long term synaptic plasticity can occur through the increased production of AMPA andNMDA glutamate receptors, among others, in the postsynaptic cell. ^[8]

In comparison, nonsynaptic plasticity is manifested through changes in the characteristics of nonsynaptic structures such as the soma, the axon, or the dendrites. Non-synaptic can have short-term or long-term effects. One way these changes occur is through modification of voltage-gated channels in the dendrites and axon, which changes the interpretation of excitatory or inhibitory potentials propagated to the cell. For example, axonal nonsynaptic plasticity can be observed when a potential fails to reach the presynaptic terminal due to low conduction or buildup of ions. ^[6]

Although synaptic plasticity was discovered and researched far before nonsynaptic plasticity, both are essential in the brain, especially to memory and learning. In fact, there is much evidence that the two mechanisms both work to achieve the observed effects, but by different mechanisms. A key example of this is in memory formation. Whereas synaptic plasticity uses the modification of presynaptic release mechanisms and postsynaptic receptors to achieve either long-term potentiation or depression, nonsynaptic plasticity has been shown to use continuous somal depolarization as a method for learned behavior and memory. In addition, nonsynaptic plasticity can add to the effects of synaptic plasticity, as in the case of voltage-gated ion channels. Nonsynaptic plasticity is the mechanism responsible for modifications of these channels in the axon, leading to a change in strength of the neuronal action potential. However, this action potential or excitability change will invariably affect the strength of synaptic mechanisms, and thus axonal plasticity aids in synaptic plasticity. ^[5] [9]