At excitatory synapses onto CA1 pyramidal cells, short-term plasticity causes synaptic strength to be modulated over a wide range in response to irregular stimulus patterns such as these synapses receive in vivo. This frequency-dependence of synaptic transmission enables computation at synapses, and determines the content of information transmitted between the pre- and post-synaptic cells. Very little is known, however, about short-term plasticity and frequency-dependence of synaptic transmission at excitatory synapses onto CA1 interneurons. Like CA1 pyramidal cells, interneurons in CA1 receive inputs from CA3 pyramidal cells via Schaffer collateral axons. However, the role of interneurons in the hippocampal circuit is quite different. Since these cells provide critical feed forward inhibition to the CA1 pyramidal cells, the frequency-dependence of their excitatory inputs will be crucial in determining the balance of excitation and inhibition in the circuit. The balance between inhibition and excitation is critical to the hippocampus, a brain region that is highly susceptible to epilepsy. Experiments in this proposal use electrophysiology to compare short-term plasticity and the frequency dependence of synaptic transmission at excitatory synapses onto CA1 interneurons vs. pyramidal cells, using traditional stimulus paradigms and temporally complex stimulus patterns based on in vivo recordings of action potential timing. These experiments will provide information about the role of the postsynaptic target cell in determining presynaptic properties, and how the frequency dependence of synaptic transmission is related to neural coding.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH065328-05
Application #
7149983
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Asanuma, Chiiko
Project Start
2002-12-01
Project End
2008-11-30
Budget Start
2006-12-06
Budget End
2008-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$240,601
Indirect Cost
Name
University of Alabama Birmingham
Department
Neurosciences
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Bartley, Aundrea F; Dobrunz, Lynn E (2015) Short-term plasticity regulates the excitation/inhibition ratio and the temporal window for spike integration in CA1 pyramidal cells. Eur J Neurosci 41:1402-15
Walters, Brandon J; Hallengren, Jada J; Theile, Christopher S et al. (2014) A catalytic independent function of the deubiquitinating enzyme USP14 regulates hippocampal synaptic short-term plasticity and vesicle number. J Physiol 592:571-86
Sun, H Y; Bartley, A F; Dobrunz, L E (2009) Calcium-permeable presynaptic kainate receptors involved in excitatory short-term facilitation onto somatostatin interneurons during natural stimulus patterns. J Neurophysiol 101:1043-55
Speed, Haley E; Dobrunz, Lynn E (2009) Developmental changes in short-term facilitation are opposite at temporoammonic synapses compared to Schaffer collateral synapses onto CA1 pyramidal cells. Hippocampus 19:187-204
Speed, Haley E; Dobrunz, Lynn E (2008) Developmental decrease in short-term facilitation at Schaffer collateral synapses in hippocampus is mGluR1 sensitive. J Neurophysiol 99:799-813
Dekay, James G T; Chang, Tony C; Mills, Nadia et al. (2006) Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development. Hippocampus 16:66-79
Sun, Hua Yu; Dobrunz, Lynn E (2006) Presynaptic kainate receptor activation is a novel mechanism for target cell-specific short-term facilitation at Schaffer collateral synapses. J Neurosci 26:10796-807
Sun, Hua Yu; Lyons, Susan A; Dobrunz, Lynn E (2005) Mechanisms of target-cell specific short-term plasticity at Schaffer collateral synapses onto interneurones versus pyramidal cells in juvenile rats. J Physiol 568:815-40