Pathway-, layer- and cell-type-specific thalamic input to mouse barrel cortex

Mouse primary somatosensory barrel cortex (wS1) processes whisker sensory information, receiving input from two distinct thalamic nuclei. The first-order ventral posterior medial (VPM) somatosensory thalamic nucleus most densely innervates layer 4 (L4) barrels, whereas the higher-order posterior thalamic nucleus (medial part, POm) most densely innervates L1 and L5A. We optogenetically stimulated VPM or POm axons, and recorded evoked excitatory postsynaptic potentials (EPSPs) in different cell-types across cortical layers in wS1. We found that excitatory neurons and parvalbumin-expressing inhibitory neurons received the largest EPSPs, dominated by VPM input to L4 and POm input to L5A. In contrast, somatostatin-expressing inhibitory neurons received very little input from either pathway in any layer. Vasoactive intestinal peptide-expressing inhibitory neurons received an intermediate level of excitatory input with less apparent layer-specificity. Our data help understand how wS1 neocortical microcircuits might process and integrate sensory and higher-order inputs.

Axonal and Dendritic Morphology of Excitatory Neurons in Layer 2/3 Mouse Barrel Cortex Imaged Through Whole-Brain Two-Photon Tomography and Registered to a Digital Brain Atlas

Sylvain Crochet, Georgios Foustoukos, Yanqi Liu, Carl Petersen

Communication between cortical areas contributes importantly to sensory perception and cognition. On the millisecond time scale, information is signaled from one brain area to another by action potentials propagating across long-range axonal arborizations. Here, we develop and test methodology for imaging and annotating the brain-wide axonal arborizations of individual excitatory layer 2/3 neurons in mouse barrel cortex through single-cell electroporation and two-photon serial section tomography followed by registration to a digital brain atlas. Each neuron had an extensive local axon within the barrel cortex. In addition, individual neurons innervated subsets of secondary somatosensory cortex; primary somatosensory cortex for upper limb, trunk, and lower limb; primary and secondary motor cortex; visual and auditory cortical regions; dorsolateral striatum; and various fiber bundles. In the future, it will be important to assess if the diversity of axonal projections across individual layer 2/3 mouse barrel cortex neurons is accompanied by functional differences in their activity patterns.

FRONTIERS MEDIA SA2022

Short-term dynamics of synaptic transmission within the excitatory neuronal network of rat layer 4 barrel cortex

Carl Petersen

The short-term plasticity of synaptic transmission between excitatory neurons within a barrel of layer 4 rat somatosensory neocortex was investigated. Action potentials in presynaptic neurons at frequencies ranging from 1 to 100 Hz evoked depressing postsynaptic excitatory postsynaptic potentials (EPSPs). Recovery from synaptic depression followed an exponential time course with best-fit parameters that differed greatly between individual synaptic connections. The average maximal short-term depression was close to 0.5 with a recovery time constant of around 500 ms. Analysis of each individual sweep showed that there was a correlation between the amplitude of the response to the first and second action potentials such that large first EPSPs were followed by smaller than average second EPSPs and vice versa. Short-term depression between excitatory layer 4 neurons can thus be termed use dependent. A simple model describing use-dependent short-term plasticity was able to closely simulate the experimentally observed dynamic behavior of these synapses for regular spike trains. More complex irregular trains of 10 action potentials occurring within 500 ms were initially well described, but during the train errors increased. Thus for short periods of time the dynamic behavior of these synapses can be predicted accurately. In conjunction with data describing the connectivity, this forms a first step toward computational modeling of the excitatory neuronal network of layer 4 barrel cortex. Simulation of whisking-evoked activity suggests that short-term depression may provide a mechanism for enhancing the detection of objects within the whisker space.

2002

Layer, cell-type and pathway-specific thalamocortical input to mouse somatosensory cortex

Berat Semihcan Sermet

In 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 cortex

EPFL2018

Layer, cell-type and pathway-specific thalamocortical input to mouse somatosensory cortex

Berat Semihcan Sermet

EPFL2018