The long-term objective of the proposed work is to characterize the plasticity at cerebellar synapses that is involved in the adaptation or learning of movements. This information will provide i) a more detailed understanding of the cerebellum and its role in the control of movements, ii) a more detailed understanding of how the mechanisms of synaptic plasticity are engaged by the behavioral events of learning, and iii) a deeper understanding of the neural building blocks of learning which may generalize to other forms of learning and other regions of the brain. Thus, this information will contribute to a better understanding of the normal, healthy mechanisms of learning, and a better understanding of pathologies of memory. Moreover, since evidence indicates that the human cerebellum also mediates certain cognitive functions, such information may be useful in identifying the neural basis of cognition and its malfunction in mental illness. Many factors combine to facilitate analysis of the cerebellum and its contribution to motor learning; these include the extensive characterization of cerebellar synaptic organization and the specific and fortuitous ways in which it is engaged by several well characterized forms of motor learning. These advantages will be exploited in the proposed studies to undertake a detailed analysis of the sites of cerebellar plasticity that mediate motor learning and the rules that govern plasticity at these sites. This analysis will also emphasize the functional significance of the interactions between these sites/rules for plasticity and the network dynamics of the cerebellum. The primary method employed will be the induction of reversible lesions through micro-infusion of various substances through cannulae implanted in critical regions. These substances will include local anesthetics that prevent all activity in the region, as well as specific agonists and antagonists of critical neurotransmitters.
The specific aims will test a series of detailed hypotheses regarding the sites and rules for synaptic plasticity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH046904-06
Application #
2033818
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Heetderks, William J
Project Start
1992-05-01
Project End
2001-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Halverson, Hunter E; Khilkevich, Andrei; Mauk, Michael D (2018) Cerebellar Processing Common to Delay and Trace Eyelid Conditioning. J Neurosci 38:7221-7236
Khilkevich, Andrei; Zambrano, Juan; Richards, Molly-Marie et al. (2018) Cerebellar implementation of movement sequences through feedback. Elife 7:
Khilkevich, Andrei; Canton-Josh, Jose; DeLord, Evan et al. (2018) A cerebellar adaptation to uncertain inputs. Sci Adv 4:eaap9660
Hoffmann, Loren C; Zara, S James; DeLord, Evan D et al. (2018) Medial Auditory Thalamus Is Necessary for Expression of Auditory Trace Eyelid Conditioning. J Neurosci 38:8831-8844
Hausknecht, Matthew; Li, Wen-Ke; Mauk, Michael et al. (2017) Machine Learning Capabilities of a Simulated Cerebellum. IEEE Trans Neural Netw Learn Syst 28:510-522
Khilkevich, Andrei; Halverson, Hunter E; Canton-Josh, Jose Ernesto et al. (2016) Links Between Single-Trial Changes and Learning Rate in Eyelid Conditioning. Cerebellum 15:112-21
Halverson, Hunter E; Hoffmann, Loren C; Kim, Yujin et al. (2016) Systematic variation of acquisition rate in delay eyelid conditioning. Behav Neurosci 130:553-62
Halverson, Hunter E; Khilkevich, Andrei; Mauk, Michael D (2015) Relating cerebellar purkinje cell activity to the timing and amplitude of conditioned eyelid responses. J Neurosci 35:7813-32
Siegel, Jennifer J (2014) Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning. J Neurophysiol 112:2123-37
Moya, Maria V; Siegel, Jennifer J; McCord, Eedann D et al. (2014) Species-specific differences in the medial prefrontal projections to the pons between rat and rabbit. J Comp Neurol 522:3052-74

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