The essential substrate for image representation in primary visual cortex is the spatiotemporal pattern of LGN input and the responses of cells and circuits within layer 4. The LGN input to cortex is dependent on time-varying patterns of excitation and inhibition and on the interactions of these processes with the intrinsic properties of relay cells, especially T-type calcium channels. Our preliminary evidence shows that these interactions are far more complex than previously thought. This is so because (a) there are at least three demonstrable types of inhibition within the LGN and (b) T-currents play a continuously graded role in shaping relay cell output rather than working in an either on or off mode as previously suggested. Further, we have demonstrated the distinct advantage of LGN cell bursts in driving the membrane potential (Vm) of layer 4 cells towards threshold as compared to the effects on isolated spikes. We will test three specific hypotheses.
In Aim 1, we will test the hypothesis that responses of LGN neurons to visual stimuli are shaped by at least three distinct forms of inhibition and that these inhibitory processes are critical to the establishment of the receptive fields of relay cells and to the shaping of their spike trains in time.
In Aim 2, we will test the hypothesis that the contribution of T- currents to LGN cell spike output is a continuously graded function of time and Vm rather than operating in an either-or fashion (burst-tonic), and, furthermore, that different types of inhibition studied in Aim 1 will engage different amounts of T-current.
In Aim 3, we will test hypotheses regarding the functional convergence of LGN afferents onto layer 4 simple cells in primary visual cortex. Specifically, we will test the hypothesis that individual layer 4 simple cells receive excitatory input from large numbers of geniculate afferents rather than to 10 to 20 suggested by extracellular studies. We will also test the hypothesis that low threshold bursts in individual LGN afferents to a given layer 4 simple cell play a decisive role in shaping cortical cell responses including the precision and information content of their spike trains. We will use a combination of intracellular recordings from LGN and cortical layer 4 and extracellular recordings from LGN using multiple tetrodes.

Public Health Relevance

Understanding cortical function and the interaction of thalamus and cortex are an essential first step towards developing clinical approaches to multiple types of brain disorders including alterations in excitability such as epilepsy or cognitive disorders such as schizophrenia. These studies represent the first systematic approach to understanding cellular and circuit function in the thalamic relay of visual inputs to cortex and in their impact on the input layer of the cerebral cortex.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Steinmetz, Michael A
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University of Pennsylvania
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Sedigh-Sarvestani, Madineh; Vigeland, Leif; Fernandez-Lamo, Ivan et al. (2017) Intracellular, In Vivo, Dynamics of Thalamocortical Synapses in Visual Cortex. J Neurosci 37:5250-5262
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Welle, Cristin G; Contreras, Diego (2016) Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry. J Neurophysiol 115:1821-35
Barz, Claudia S; Bessaih, Thomas; Abel, Ted et al. (2016) Altered resonance properties of somatosensory responses in mice deficient for the schizophrenia risk gene Neuregulin 1. Brain Struct Funct 221:4383-4398
Denman, Daniel J; Contreras, Diego (2016) On Parallel Streams through the Mouse Dorsal Lateral Geniculate Nucleus. Front Neural Circuits 10:20
Vanleer, Ann C; Blanco, Justin A; Wagenaar, Joost B et al. (2016) Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures. J Neural Eng 13:026015
Denman, Daniel J; Contreras, Diego (2015) Complex Effects on In Vivo Visual Responses by Specific Projections from Mouse Cortical Layer 6 to Dorsal Lateral Geniculate Nucleus. J Neurosci 35:9265-80
Denman, Daniel J; Contreras, Diego (2014) The structure of pairwise correlation in mouse primary visual cortex reveals functional organization in the absence of an orientation map. Cereb Cortex 24:2707-20
Vigeland, Leif E; Contreras, Diego; Palmer, Larry A (2013) Synaptic mechanisms of temporal diversity in the lateral geniculate nucleus of the thalamus. J Neurosci 33:1887-96
Wester, Jason C; Contreras, Diego (2013) Differential modulation of spontaneous and evoked thalamocortical network activity by acetylcholine level in vitro. J Neurosci 33:17951-66

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