Huntingtin (HTT) occurs in the neuronal cytoplasm and can interact with structural elements of synapses. Huntington's disease (HD) results from pathological expansion of a polyglutamine stretch in the HTT molecule, being probably associated with aberrant protein-protein interactions. The pathogenetic mechanism is still incompletely understood. Alterations of the synaptic structure and plasticity in the hippocampus are observed in early HD. The objective of the study was to theoretically evaluate the HTT contribution to changes in synaptic plasticity by integrating the available experimental data. HTT protein complexes are involved in maintaining the efficiency of synaptic transmission. A pathogenic HTT form (polyQ-HTT) probably disrupts the protein-protein interactions in distorts the dynamics of molecular processes in the synapsis. It was assumed that polyQ-HTT may compete with postsynaptic density proteins and proteins regulating cytoskeleton remodeling.
Traditionally, studies of the neurobiology of learning and memory focus on the circuitry that interfaces between sensory inputs and behavioral outputs, such as the amygdala and cerebellum. However, evidence is accumulating that some forms of learning can in fact drive stimulusspecifc changes very early in sensory systems, including not only primary sensory cortices but also precortical structures and even the peripheral sensory organs themselves. In this study, we investigated the effect of olfactory associative training on the functional activity of olfactory epithelium neurons in response to an indifferent stimulus (orange oil). It was found that such a peripheral structure of the olfactory system of adult mice as the olfactory epithelium (OE) demonstrates experiencedependent plasticity. In our experiment, associative learning led to changes in the patterns of OE cell activation in response to orange oil in comparison with the control group and animals that were given odor without reinforcement. To interpret the results obtained, we compared the distribution of MRI contrast across the zones of OE in response to a conditioned odor in trained animals and in control animals that were given orange oil at three concentrations: original (used for conditioning), 4fold higher and 4fold lower. Since the OE activation patterns obtained coincided in the group of trained animals and controls, which were stimulated with orange oil at the 4fold higher concentration, it can be concluded that associative conditioning increased the sensitivity of the OE to the conditioned stimulus. The observed increase in OE response to orange oil may be the result of neurogenesis, i. e. the maturation of new olfactory neurons responsive to this stimulus, or the consequence of an increase in individual sensitivity of each OE neuron. Based on data of MRI contrast accumulation in mouse OE, the sensory plasticity way in learninginduced increase in sensitivity of OE to conditioned stimulus is more possible. Thus, the sensory plasticity of the OE plays a signifcant role in the formation of the neuronal response to the provision of an initially indifferent odor and is part of the adaptive responses to the environmental changing.
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