The long term objectives of the present proposal is to study the physiology, and plasticity of excitatory synapses in the rat visual cortex. Specifically the aims of this proposal are: 1) Analysis of the excitatory synaptic input to non-pyramidal neurons in layer IV and to pyramidal neurons in layer II/III; 2) Analysis of the unitary connection between cells in the visual cortex; 3) Quantal Analysis of the EPSC; 4) Analysis of long term synaptic potentiation in layer IV and lI/III neurons. At the present, much is known about the anatomy of the visual cortex and about the light response characteristics of visual cortical neurons. It has been observed that synaptic connections in the visual cortex can undergo long term potentiation (LTP) following high frequency stimulation. However, because of technical difficulties, relatively little is known about the specific neurons that are involved in LTP and the mechanisms underlying its induction and expression. It is proposed here to use a new method of recording which allows visualization of individual neurons in live brain slices in combination with a high-resolution whole-cell recording. Stimulation of the thalamic afferents would be achieved by extracellular stimulation in close vicinity to the main dendrites. Stimulation of local excitatory neurons would be achieved by an intracellular stimulation of paired neurons. Under these conditions, the amplitude and subtype(s) of the unitary monosynaptic EPSCs would be determined. This data would than be used to examine the role of post-synaptic and pre-synaptic activation in inducing LTP. In addition, the change which occurs with LTP would be examined. This would be achieved by determining the EPSC quantal amplitude and by morphological measurements (using intensified epifluorescence) of the pre-synaptic terminal and post-synaptic dendritic spines before and after the induction of LTP.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009120-02
Application #
3266504
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1991-05-01
Project End
1994-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kim, Juhyun; Matney, Chanel J; Blankenship, Aaron et al. (2014) Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a. J Neurosci 34:9656-64
Brown, Solange P; Hestrin, Shaul (2009) Cell-type identity: a key to unlocking the function of neocortical circuits. Curr Opin Neurobiol 19:415-21
Brown, Solange P; Hestrin, Shaul (2009) Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Nature 457:1133-6
Galarreta, Mario; Erdelyi, Ferenc; Szabo, Gabor et al. (2008) Cannabinoid sensitivity and synaptic properties of 2 GABAergic networks in the neocortex. Cereb Cortex 18:2296-305
Zsiros, Veronika; Hestrin, Shaul (2005) Background synaptic conductance and precision of EPSP-spike coupling at pyramidal cells. J Neurophysiol 93:3248-56
Hestrin, Shaul; Galarreta, Mario (2005) Electrical synapses define networks of neocortical GABAergic neurons. Trends Neurosci 28:304-9
Galarreta, Mario; Erdelyi, Ferenc; Szabo, Gabor et al. (2004) Electrical coupling among irregular-spiking GABAergic interneurons expressing cannabinoid receptors. J Neurosci 24:9770-8
Chu, Zhiguo; Galarreta, Mario; Hestrin, Shaul (2003) Synaptic interactions of late-spiking neocortical neurons in layer 1. J Neurosci 23:96-102
Galarreta, M; Hestrin, S (2001) Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292:2295-9
Galarreta, M; Hestrin, S (2000) Burst firing induces a rebound of synaptic strength at unitary neocortical synapses. J Neurophysiol 83:621-4

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