Carsten Klein

Investigation of thalamo-cortical connectivity in the primate brain with cell-targeted optogenetics and electrical micro-stimulation

The primate brain consists of various types and classes of cells that form anatomically segregated structures generally referred to as nuclei or areas which are highly interconnected within and between each other. Disentangling these connections on a functional and anatomical level is a major challenge in neuroscience. While anatomical tract tracing studies reveal the physical basis of neuronal connectivity within the brain, conclusions about their functional relevance are hard to derive from histological data alone. Likewise functional data obtained with electrophysiological recordings usually lacks the relevant underlying anatomical information. It is therefore desirable to combine anatomical and physiological data in order to unravel the functions of brain circuits.

In my work I investigate the connectivity of the lateral geniculate nucleus (LGN) with the primary visual cortex (V1) of the macaque monkey on a functional level with cell targeted optogenetics and electrical micro-stimulation. The LGN consist of three distinct neuronal subpopulations that relay information to V1, the magno-, parvo and konio cells. While much is known about the magno- and parvo-LGN cells the function of the konio cells is still not fully understood. Unlike the magno- and parvo-LGN cells which express the calcium binding protein parvalbumin konio LGN cells express another calcium binding protein called CamKII?. This exclusive expression of CamKII? within LGN konio neurons allows their selective manipulation through CamKII? targeted optogenetics. In optogenetics neurons become responsive to direct light stimulation through the genetically enforced expression of light sensitive proteins called opsins. Therefore through the selective optogenetic stimulation of LGN konio cells their role in visual processing and their impact on V1 function can be studied in vivo.

The anatomical organization of the LGN into three segregated relay cell populations with little internal recurrence further offers the opportunity to directly compare the method of optogenetics to the less cell type specific method of electrical micro-stimulation. Results obtained in this project highlight the value of both stimulation techniques to investigate large scale brain circuits in primates.

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