The cerebellum and its connections with other parts of the brain act as functional loops that underlie various aspects of motor control, learning, attention, language, working memory, and emotion. Disruption of these functional loops may be the basis for symptoms of schizophrenia, bipolar disorder, autism, fragile X syndrome, and other disorders. The current proposal is designed to examine sensory inputs to the cerebellum that are necessary for learning and to determine whether the cerebellum sends feedback to these sensory inputs during learning. Pavlovian eyeblink conditioning will be used as the method for assessing cerebellar learning. Previous findings from this project identified the neural pathway necessary for auditory eyeblink conditioning, which includes the medial auditory thalamus (MAT) and its projections to the pontine nuclei. MAT neurons exhibit learning-related changes in activity during eyeblink conditioning that are hypothesized to be driven by feedback from the cerebellum.
The first aim of the current proposal is to identify the neural pathway(s) necessary for visual eyeblink conditioning and to determine whether the visual thalamus also shows learning-related activity using reversible inactivation and high-density neuronal recording methods.
Aim 2 is to determine whether learning-related activity in the thalamus is driven by the cerebellum or its downstream target nuclei by recording neuronal activity in the thalamus while inactivating the cerebellum and its target nuclei.
Aim 3 will investigate the mechanisms underlying cross-modal facilitation of cerebellar learning using high- density neuronal recording methods.
Aim 4 is to determine the roles of auditory and visual areas of the cerebral cortex in cerebellar learning using reversible inactivation. The proposed project will significantly increase knowledge about the nature of cerebellar interactions with sensory areas of the brain that underlie associative learning. Findings from this project could be used to develop methods for treating various symptoms caused by pathology in cerebellar interactions with other brain areas.

Public Health Relevance

The cerebellum and its connections with other brain areas act as functional loops that contribute to movement, attention, working memory, learning, timing perception, language, and executive control. Pathology in the cerebellum or its connections with other brain areas may be the basis for the symptoms of schizophrenia, bipolar disorder, fragile X syndrome, autism, and other disorders. The proposed research will examine the mechanisms of cerebellar interactions with sensory systems. The findings of this project could be used to develop methods for treating various symptoms caused by pathology in cerebellar interactions with other brain areas.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01MH080005-08
Application #
8659492
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Iowa
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Freeman, John H (2015) Cerebellar learning mechanisms. Brain Res 1621:260-9
Steinmetz, Adam B; Harmon, Thomas C; Freeman, John H (2013) Visual cortical contributions to associative cerebellar learning. Neurobiol Learn Mem 104:103-9
Steinmetz, Adam B; Freeman, John H (2013) Differential effects of the cannabinoid agonist WIN55,212-2 on delay and trace eyeblink conditioning. Behav Neurosci 127:694-702
Campolattaro, Matthew M; Kashef, Alireza; Lee, Inah et al. (2011) Neuronal correlates of cross-modal transfer in the cerebellum and pontine nuclei. J Neurosci 31:4051-62
Halverson, Hunter E; Freeman, John H (2010) Medial auditory thalamic input to the lateral pontine nuclei is necessary for auditory eyeblink conditioning. Neurobiol Learn Mem 93:92-8
Halverson, Hunter E; Lee, Inah; Freeman, John H (2010) Associative plasticity in the medial auditory thalamus and cerebellar interpositus nucleus during eyeblink conditioning. J Neurosci 30:8787-96
Campolattaro, Matthew M; Freeman, John H (2009) Cerebellar inactivation impairs cross modal savings of eyeblink conditioning. Behav Neurosci 123:292-302
Campolattaro, Matthew M; Freeman, John H (2009) Examination of bilateral eyeblink conditioning in rats. Behav Neurosci 123:1346-52
Plakke, Bethany; Freeman, John H; Poremba, Amy (2009) Metabolic mapping of rat forebrain and midbrain during delay and trace eyeblink conditioning. Neurobiol Learn Mem 92:335-44
Halverson, Hunter E; Poremba, Amy; Freeman, John H (2008) Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning. Learn Mem 15:532-8

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