Inhibitory (GABAergic) neurons constitute about 15-30 percent of cells in the neocortex and are classified into distinct groups according to their morphology and histochemistry. However, the functional significance of this diversity and the characteristics of inhibitory interactions of specific types of GABAergic neurons in terms of local circuit organization and the processing of information in the neocortex are only poorly understood. We have developed methods allowing us to identify and study interactions of specific types of inhibitory neurons. Using these methods we have shown that a prominent class of inhibitory neurons, the fast-spiking (FS) cells, is specifically and extensively interconnected via electrical synapses. Furthermore, we have found that the FS cell network can produce synchronous spiking and can be sensitive to coincident activity. In preliminary studies we have found extensive electrical synapses among another class of cells located in layer 1 termed late-spiking (LS) cells. Together, these data lead us to hypothesize that specific synaptic connections of different classes of inhibitory neurons form GABAergic networks that coordinate activity in the neocortex. The long-term goals of this proposal are to study how different classes of inhibitory interneurons are organized in terms of their specific synaptic interactions and to study the functional implications of these interactions for the processing of information in the visual cortex. We propose to address the following three specific aims: 1. Physiological properties of GABAergic synapses made by FS cells and LS cells. 2. Properties of electrical synapses among FS cells and among LS cells. 3. Emergent properties of networks formed by FS cells and LS cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012114-09
Application #
6872847
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Oberdorfer, Michael
Project Start
1998-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
9
Fiscal Year
2005
Total Cost
$395,013
Indirect Cost
Name
Stanford University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Huh, Carey Y L; Peach, John P; Bennett, Corbett et al. (2018) Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex. Curr Biol 28:114-120.e5
Arroyo, Sergio; Bennett, Corbett; Hestrin, Shaul (2018) Correlation of Synaptic Inputs in the Visual Cortex of Awake, Behaving Mice. Neuron 99:1289-1301.e2
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
Bennett, Corbett; Arroyo, Sergio; Hestrin, Shaul (2014) Controlling brain states. Neuron 83:260-261
Bennett, Corbett; Arroyo, Sergio; Hestrin, Shaul (2013) Subthreshold mechanisms underlying state-dependent modulation of visual responses. Neuron 80:350-7
DeFelipe, Javier; López-Cruz, Pedro L; Benavides-Piccione, Ruth et al. (2013) New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat Rev Neurosci 14:202-16
Arroyo, Sergio; Bennett, Corbett; Aziz, David et al. (2012) Prolonged disynaptic inhibition in the cortex mediated by slow, non-ýý7 nicotinic excitation of a specific subset of cortical interneurons. J Neurosci 32:3859-64
Bennett, Corbett; Arroyo, Sergio; Berns, Dominic et al. (2012) Mechanisms generating dual-component nicotinic EPSCs in cortical interneurons. J Neurosci 32:17287-96
Hestrin, Shaul (2011) Noradrenaline enhances signal-to-noise ratio of inhibitory inputs in the dorsal cochlear nucleus. Neuron 71:197-8
Hestrin, Shaul (2011) Neuroscience. The strength of electrical synapses. Science 334:315-6

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