The main goal of this dissertation was to identify eyeblink projection neurons of the anterior interpositus nucleus (AIN) and to examine learning-specific changes in excitatory and inhibitory somatic synapses after eyeblink conditioning (EBC). In order to identify the specific subset of AIN neurons involved in EBC, a retrograde transneuronal viral tracer was injected into the eyelid (orbicularis oculi muscle) of the rabbit to reveal hierarchical chains of synaptically connected neurons involved in the eyeblink response. Experiment 1 was designed to provide a complete delineation of the rabbit eyeblink premotor pathway and to characterize the multiple neuronal types in the AIN that are involved in EBC and their possible interactions. Relevant structures involved in the generation or modulation of the rabbit eyeblink response were identified and possible sites of plasticity were revealed. First-order eyeblink motoneurons were found ipsilaterally in the dorsolateral facial nucleus. Second-order premotor neurons were found in the contralateral red nucleus and in different reticular, trigeminal, auditory, and vestibular nuclei. Third-order eyeblink premotor neurons were found in the pons, midbrain, and in the cerebellum, including dorsolateral AIN and rostral fastigial nucleus. Fourth-order neurons were found in Purkinje cells of the cerebellar cortex in lobule HVI and in lobule I. Eyeblink premotor neurons of the AIN were further characterized based on their neurotransmitter immunoreactivity which showed that glutamatergic eyeblink projection neurons are modulated by three different types of inhibitory interneurons that form a functional eyeblink microcomplex. Experiment 2 was designed to examine the effect of EBC on the number of excitatory and inhibitory somatic synapses in eyeblink projection neurons of the AIN. A coordinated increase in the number of excitatory and inhibitory Purkinje cell somatic synapses was observed in subjects in the experimental group that received paired delay EBC. These results support a parallel and correlated mechanism of cerebellar learning mediated by excitatory inputs presumably from mossy fibers and inhibitory inputs from Purkinje cells. In contrast, control subjects that received unpaired stimulus presentations showed an increase in the number of inhibitory somatic synapses originating from local interneurons, suggesting a possible role of feedback inhibition that may also explain the detrimental effect of unpaired exposure on subsequent learning. Another important finding was an increase in the somatic surface area of eyeblink projection neurons as a function of learning that was highly correlated with the number of somatic synapses; suggesting that synaptic remodeling is a bidirectional process that entails proportional structural alterations on the postsynaptic neuron. To our knowledge, this is the first time that the identity and function of specific nuclear neurons and their associated synaptic changes during learning can be linked to a behavior.
|Advisor:||Schreurs, Bernard G.|
|Commitee:||Berrebi, Albert S., Salm, Adrienne K., Sokolov, Maxim, Spirou, George A.|
|School:||West Virginia University|
|School Location:||United States -- West Virginia|
|Source:||DAI-B 76/02(E), Dissertation Abstracts International|
|Keywords:||Cerebellar learning, Cerebellum, Eyeblink conditioning, Interpositus, Synaptic plasticity|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be