All visual information is conveyed to the cortex via geniculocortical (GC) synapses, yet how GC inputs drive intracortical interactions is only poorly understood. The common view is that visual activation, initiated in the retina, is relayed through the lateral geniculate nucleus (LGN) to layer 4 (L4) neurons. Activity then flows through the cortex from L4 to layer 2/3 (L2/3), then layer 5 (L5) followed by layer 6 (L6). However, several lines of evidence suggest that this description is grossly simplified. First, while anatomical studies show that GC axons primarily innervate L4 and lower L3, additional GC terminals target L6 and L1. Although the innervation of L6 and L1 is relatively modest anatomically, the functional impact of these synaptic inputs may be significant. Thalamic input will drive these different layers in parallel, and its impact will depend on intracortical interactions among the thalamorecipient cells. Second, the synaptic strength and dynamics of GC synapses may play an important role in shaping the transmission of visual information to the cortex. Whether geniculocortical synapses are exceptionally efficacious and reliable is controversial. Different classes of geniculate relay neurons may exhibit distinct synaptic properties, but this has not been explored. Furthermore, GC inputs target different classes of excitatory and inhibitory neurons, and the identity of the cortical postsynaptic targets may also influence the functional properties of GC synapses. Diversity in the synaptic properties of GC synapses could change the balance of excitation and inhibition during ongoing GC activity, profoundly affecting cortical processing of visual information. To address these issues, we will selectively express a light-gated cation channel, channelrhodopsin-2 (ChR2), in GC neurons to optically stimulate GC fibers in isolation. Combined with our extensive experience in targeted recording from different classes of inhibitory and excitatory neurons in visual cortex, this novel approach will allow us to develop a comprehensive view of how different GC inputs drive cortical circuits during ongoing visual stimulation.

Public Health Relevance

The proposed experiments will uncover mechanisms that underlie the flow of visual information through the brain. Understanding these mechanisms will further our understanding of normal brain function and facilitate the diagnosis and treatment of neurological and psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012114-13
Application #
8138467
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Steinmetz, Michael A
Project Start
1998-04-01
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
13
Fiscal Year
2011
Total Cost
$383,263
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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