Sensory-motor systems must be recalibrated to adapt to normally-occurring or pathologically-induced changes in the pattern of sensory inputs. For studies of this process, the key questions are pinpointing how the system is appraised of changes in its sensory inputs, and defining the mechanisms by which an adaptive response is generated. This highlights a general problem for excitable cells which is how to scale or vary their responses appropriately with changes in the quantity or pattern of their synaptic inputs. In many cases, critical changes in synaptic activity are communicated to neurons via N-methyl-D- aspartate (NMDA) or metabotropic (mGlu) type glutamate receptors. We propose to use a simple system--the electromotor system of electric fish, which controls the electric organ discharge (EOD)- -to study how alterations in sensory inflow can regulate the activity of motor output circuitry to adaptively change the circuit's and the animal's behavior. These alterations in the sensory inflow are processed in the CNS and ultimately communicated to the pacemaker neurons that control the EOD frequency via NMDA and, possibly, mGlu receptors. Activation of these receptors leads to long-term (many hours) adaptive changes in the firing frequency of these critical pacemaking neurons after the stimulus has ceased. In this proposal we wish to more fully characterize how sensory stimuli induce long-term shifts in motor output (EOD frequency) of behaving animals; identify in a slice preparation how activation of NMDA and mGlu receptors in pacemaking neurons could lead to long-term changes in their postsynaptic firing rates; and, finally, test the role of these receptors in controlling the behavior by blocking them in pacemaking neurons in a restrained behaving animal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH056535-07
Application #
6683639
Study Section
Special Emphasis Panel (ZRG1-IFCN-5 (01))
Program Officer
Asanuma, Chiiko
Project Start
1996-12-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2005-11-30
Support Year
7
Fiscal Year
2004
Total Cost
$225,000
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
George, Andrew A; Macleod, Gregory T; Zakon, Harold H (2011) Calcium-dependent phosphorylation regulates neuronal stability and plasticity in a highly precise pacemaker nucleus. J Neurophysiol 106:319-31
Dembrow, Nikolai C; Pettit, Diana L; Zakon, Harold H (2010) Calcium dynamics encode the magnitude of a graded memory underlying sensorimotor adaptation. J Neurophysiol 103:2372-81
Oestreich, Jorg; Dembrow, Nikolai C; George, Andrew A et al. (2006) A ""sample-and-hold"" pulse-counting integrator as a mechanism for graded memory underlying sensorimotor adaptation. Neuron 49:577-88
Bass, Andrew H; Zakon, Harold H (2005) Sonic and electric fish: at the crossroads of neuroethology and behavioral neuroendocrinology. Horm Behav 48:360-72
Oestreich, Jorg; Zakon, Harold H (2005) Species-specific differences in sensorimotor adaptation are correlated with differences in social structure. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 191:845-56
Dunlap, Kent D (2002) Hormonal and body size correlates of electrocommunication behavior during dyadic interactions in a weakly electric fish, Apteronotus leptorhynchus. Horm Behav 41:187-94
Tallarovic, S K; Zakon, H H (2002) Electrocommunication signals in female brown ghost electric knifefish, Apteronotus leptorhynchus. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 188:649-57
Zakon, Harold; Oestreich, Joerg; Tallarovic, Sara et al. (2002) EOD modulations of brown ghost electric fish: JARs, chirps, rises, and dips. J Physiol Paris 96:451-8
Oestreich, Jorg; Zakon, Harold H (2002) The long-term resetting of a brainstem pacemaker nucleus by synaptic input: a model for sensorimotor adaptation. J Neurosci 22:8287-96
Smith, G T; Zakon, H H (2000) Pharmacological characterization of ionic currents that regulate the pacemaker rhythm in a weakly electric fish. J Neurobiol 42:270-86

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