The goal of the proposed project is to determine the basic mechanisms of synaptic plasticity and functional circuitry in the electrosensory lobe (ELL) of mormyrid electric fish. The ELL is a cerebellum-like structure where the primary afferent fibers from electroreceptors terminate. The ELL of the mormyrid electric fish and similar cerebellumlike structures in other fish are adaptive sensory processors in which memory-like predictions about sensory input are generated and subtracted from current sensory input, allowing neural responses to unexpected or novel input to stand out. The predictions are based on prior associations between sensory input and various central signals conveyed by parallel fibers such as corollary discharge signals linked to motor commands. Plasticity at the excitatory synapse between parallel fibers and ELL cells has been established in in vitro slices. This synaptic plasticity is probably at least partly responsible for the systems-level generation of memory-like predictions. The plasticity is observed after a few minutes of pairing a presynaptic parallel fiber input with a postsynaptic spike. The plasticity includes an associative depression that depends on the relative timing of pre- and postsynaptic spikes and a non-associative potentiation. The potentiation can reverse the depression and vice versa, indicating that both processes affect a common cellular site. Recent findings suggest that this common site of action is in the presynaptic terminal of parallel fibers.
The Specific Aims of the proposed project are: 1) to determine the basic mechanisms of the plasticity established at parallel fiber synapses in ELL; 2) to determine whether plasticity also occurs at inhibitory synapses in ELL; and 3) to determine basic features of ELL circuitry. The results of this research will enhance our understanding of synaptic plasticity at the cellular level and the role of such plasticity in memory-like functions. The results may also be a source of insight into other cerebellum-like structures, such as the dorsal cochlear nucleus of mammals or the cerebellum itself.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049792-13
Application #
7112432
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Glanzman, Dennis L
Project Start
1994-09-30
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
13
Fiscal Year
2006
Total Cost
$257,543
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Meek, Johannes; Yang, Jianji Y; Han, Victor Z et al. (2008) Morphological analysis of the mormyrid cerebellum using immunohistochemistry, with emphasis on the unusual neuronal organization of the valvula. J Comp Neurol 510:396-421
Bell, Curtis C; Han, Victor; Sawtell, Nathaniel B (2008) Cerebellum-like structures and their implications for cerebellar function. Annu Rev Neurosci 31:1-24
Han, Victor Z; Zhang, Yueping; Bell, Curtis C et al. (2007) Synaptic plasticity and calcium signaling in Purkinje cells of the central cerebellar lobes of mormyrid fish. J Neurosci 27:13499-512
Zhang, Jianmei; Han, Victor Z; Meek, Johannes et al. (2007) Granular cells of the mormyrid electrosensory lobe and postsynaptic control over presynaptic spike occurrence and amplitude through an electrical synapse. J Neurophysiol 97:2191-203
Campbell, Holly R; Meek, Johannes; Zhang, Jianmei et al. (2007) Anatomy of the posterior caudal lobe of the cerebellum and the eminentia granularis posterior in a mormyrid fish. J Comp Neurol 502:714-35
Han, Victor Z; Meek, Johannes; Campbell, Holly R et al. (2006) Cell morphology and circuitry in the central lobes of the mormyrid cerebellum. J Comp Neurol 497:309-25
Sawtell, Nathaniel B; Williams, Alan; Roberts, Patrick D et al. (2006) Effects of sensing behavior on a latency code. J Neurosci 26:8221-34
Bell, Curtis C; Meek, Johannes; Yang, Jianji Y (2005) Immunocytochemical identification of cell types in the mormyrid electrosensory lobe. J Comp Neurol 483:124-42
Sawtell, Nathaniel B; Williams, Alan; Bell, Curtis C (2005) From sparks to spikes: information processing in the electrosensory systems of fish. Curr Opin Neurobiol 15:437-43
Han, Victor Z; Bell, Curtis C (2003) Physiology of cells in the central lobes of the mormyrid cerebellum. J Neurosci 23:11147-57

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