Petersen, CarlSermet, Berat Semihcan2018-11-212018-11-212018-11-21201810.5075/epfl-thesis-9064https://infoscience.epfl.ch/handle/20.500.14299/151555In the mouse whisker system, sensory information is relayed to the whisker somatosensory cortex by two major thalamic nuclei, the ventral posterior medial nucleus (VPM) and the posterior medial nucleus (POM). While the cortical axonal innervation pattern of these two nuclei has been studied anatomically in some detail, their synaptic input to distinct cell-types across different layers in barrel cortex is incompletely understood. I used the specificity of optogenetics to selectively stimulate axons from VPM or POM, and I measured the evoked excitatory postsynaptic potentials in vitro with whole-cell patch-clamp recordings in primary whisker somatosensory cortex (wS1). VPM or POM was infected in vivo with an adenoassociated virus (AAV) encoding the light-gated cation channel channelrhodopsin (ChR2). Synaptic input onto individual neurons of the barrel cortex was recorded in brain slices in vitro by activating the ChR2-expressing thalamic axons with blue light. I measured thalamic inputs onto excitatory and three distinct classes of GABAergic neurons, expressing Parvalbumin (PV), somatostatin (SST) or vasoactive intestinal peptide (VIP) neurons across all layers of the barrel cortex. In excitatory and PV neurons, I found that the biggest inputs appeared to largely colocalize with the anatomical innervation pattern Anatomically, VPM preferentially innervates layer4 (L4), deep L3 and the L5B/6A border, and, functionally, we found that the biggest input was observed in L4, followed by L3. Anatomically, POM innervates L5A and L1, and, functionally, I found the biggest input in L5A. SST neurons received very weak input from both thalamic nuclei. VIP neurons on the other hand received larger inputs than SST neurons, however, they were weaker than excitatory and PV neurons. POM is considered to have both first-order and higher-order properties and I, therefore, began to investigate connectivity within sub-parts of POM. Taking advantage of a recently developed anterograde transsynaptic AAV injected into somatosensory brainstem nuclei, I defined first-order and higher-order sub-nuclei of POM and investigated their functional connectivity with somatosensory cortex. Anatomically, the first-order POM preferentially innervates L4 of the secondary somatosensory cortex (wS2) and functionally, I found that neurons across many layers in wS2 received direct synaptic input from first-order POM. Higher-order POM innervates both wS2 and wS1, and I found that neurons in wS2 also receive direct synaptic input. The data suggest that first-order POM relays sensory information to wS2, apparently in a parallel signaling pathway to the classical VPM to wS1 sensory pathway. In contrast, higher order POM does not appear to receive direct sensory input from the brainstem Our results begin to provide a more complete understanding of the distribution of thalamic input to specific cell-types across the layers of the mouse somatosensory cortexenOptogeneticsChannelrhodopsin-2adeno associated viruswhisker somatosensory cortexthalamusventral posterior medial nucleusposterior medial nucleuspostsynaptic potentialmembrane potentialthesis::doctoral thesis