Separate classes of inhibitory neurons target proximal and distal regions at pyramidal cells and thus impact differentially the processing of visual information in the cortex. However, the mechanisms that allow selective activation of specific classes of inhibitory neurons are unknown. In this proposal we will study the pre- and postsynaptic mechanisms activating specific classes of inhibitory neurons. We will test the hypothesis that inhibitory neurons targeting proximal vs. distal pyramidal cell regions differ in the temporal integration of their excitatory inputs. More specifically, we will test the proposal that spike timing is important at proximally targeting fast-spiking (FS) cells, whereas late-spiking (LS) and low threshold spiking (LTS) cells, inhibiting distal dendrites, integrate their excitatory inputs over a prolonged period of time.
The specific aims are:
Specific Aim 1 : We will compare the functional properties of AMPA and NMDA receptors mediating EPSPs at FS inhibitory neurons, targeting the soma and proximal dendrites of pyramidal cells, and at LS and LTS cells, targeting distal dendrites.
Specific Aim 2 : We will compare how postsynaptic voltage-dependent mechanisms determine the way different patterns of EPSPs are integrated and produce action potentials at proximally targeting FS cell and at distally targeting LS and LTS GABAergic interneuron.
Specific Aim 3 : We will study the developmental and experience-dependent regulation of excitatory synapses in proximally and distally targeting GABAergic interneurons.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009120-16
Application #
6888114
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Oberdorfer, Michael
Project Start
1993-08-01
Project End
2008-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
16
Fiscal Year
2005
Total Cost
$399,693
Indirect Cost
Name
Stanford University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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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