Sensory information, such as a visual scene, is broken down (encoded) in the early visual pathway into features which increase in complexity before being tied together (decoded) in higher brain areas. The thalamocortical projection of the visual pathway is involved in encoding, such that neurons in the thalamic population transform the visual input very differently than neurons one synapse away in the input layers of visual cortex. We do not understand the underlying circuits that contribute to this transformation of visual input at the thalamocortical synapse. One complication is that cortical cells which receive direct thalamic input also receive input from other nearby cortical cells, so it is difficult to understand the role of the thalamic input. The goal of this proposal is to tease apart the thalamocortical circuit by simultaneous observation and manipulation of the pre and post-synaptic population, in the thalamus and cortex respectively. We propose two novel techniques to study single thalamocortical synapses and to isolate the contribution of the thalamic projection to response properties of cortical cells.
In Aim 1, we will use simultaneous extracellular recordings of many LGN (lateral geniculate nucleus of the thalamus) cells with intracellular recording of a cortical cell to study synaptic connections. This will allow us to directly study the LGN population that converges onto a cortical cell.
In Aim 2 we take advantage of this prep by adding dynamic clamp, which we use to create monosynaptic connections in vivo. Dynamic clamp is a method similar to current clamp, which allows the 'injection' of fixed conductances into a cell. We will generate the conductance that will be injected to the cortical cell by by triggering synaptic conductance injections based on the spike time of a population of LGN cells. We can select this population and manipulate their spiking output in desired ways. We will also ensure that the cortical cell only receives visual input from the conductance injections. This allows us to study the response properties of the cortical cell as a function of the properties of the input thalamic population. Collectively, these studies will define several important but unknown properties of thalamocortical synapses and will test several existing hypotheses regarding visual encoding, leading to improved understanding of visual processing.

Public Health Relevance

Understanding cortical function is an essential first step towards developing clinical approaches to addressing multiple types of brain disorders including epilepsy or schizophrenia. These studies represent a systematic approach to understanding cellular and circuit function in the thalamocortical circuit of the visual cortex, and have relevane to all other sensory cortices.

National Institute of Health (NIH)
National Eye Institute (NEI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Agarwal, Neeraj
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Max Planck Florida Corporation
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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