Brainstem

Summary

The brainstem (or brain stem) is the stalk-like part of the brain that interconnects the cerebrum and diencephalon with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is continuous with the thalamus of the diencephalon through the tentorial notch. The brainstem is very small, making up around only 2.6 percent of the brain's total weight. It has the critical roles of regulating cardiac, and respiratory function, helping to control heart rate and breathing rate. It also provides the main motor and sensory nerve supply to the face and neck via the cranial nerves. Ten pairs of cranial nerves come from the brainstem. Other roles include the regulation of the central nervous system and the body's sleep cycle. It is also of prime importance in the conveyance of motor and sensory pathways from the rest of the brain to the body, and

Official source

https://en.wikipedia.org/wiki/Brainstem

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Conformable neural interfaces : from engineering stretchability at the micro-scale to translational applications

Florent-Valéry Coen

Recently, flexible and soft bioelectronic interfaces have been proposed as a solution to improve existing neural interfaces that currently present mechanical mismatch with the soft tissue. These are devices fabricated with thin polymeric or elastomeric backbones to enable an optimal contact to the target tissue as well as reduced mechanical mismatch. For this the electrical interconnects that carry the electrical information from the tissue or deliver the stimulation charges need to be elastic to accommodate the stresses and remain conductive. Several strategies for creating stretchable tracks have been proposed in the past but are not compatible with high-density low-profile electrode arrays for chronic implantation in vivo.A method of patterning thin material stacks of flexible polymers and platinum layers embedded in silicone membranes was proposed in the Laboratory for Soft Bioelectronic Interfaces at EPFL. By creating specific microscopic cuts in the materials permits the out-of-plane deformation of the film and enables stretchability above 50% strain while remaining conductive. However, the previous fabrication method was not optimal, was not hermetically encapsulated and not reliable. In this thesis, novel soft electrode arrays were designed and fabricated using an improved manufacturing process named core-shell micropatterning. This enables fully encapsulated electrical tracks that can be micropatterned with superior electromechanical performances and notable increase in hermetic barrier lifetimes. Additionally, this method was applied to other material systems enabling new functions such as completely transparent devices to enable concurrent optical stimulation and microscopy through the implanted electrodes.These fabricated devices were applied to several device concepts in multiple animal models. First, microelectrode arrays for electrocorticography (ECoG) recordings were designed to be implanted over the auditory cortex of rat and non-human primate (NHP) models to capture evoked potentials from acoustic stimulation. This enabled the precise tonotopic mapping and the spatial representation of the auditory cortex. Next, auditory brainstem implants (ABI), targeting the cochlear nucleus (CN) after the auditory nerve were designed. This implant needs to conform to the curved surface of the CN and stimulate the auditory pathway. In non-human primates, the placement of this device is challenging and new tools were developed for the insertion of the device. Finally, the combination of soft ABI and ECoG was implanted in chronic settings in a NHP to evoke auditory percepts from brainstem stimulation that could be monitored using the cortical evoked potentials. This will enable the fine-tuning of stimulation protocols for hearing restoration and verify the stability of the implants over time.Overall, this work represents a framework to design and fabricate soft electrode arrays that can be applied for recording and stimulation in small to large animal models in a reliable way. The careful design of the system around the implant such as fine-tuning of microfabrication parameters, the characterization in vitro, device geometry, connection scheme, experimental setup and tracking of the device properties in vivo enables reliable long-term implantations in new experimental paradigms.

EPFL2022

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

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Subdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices. The thalamus provides sensory input to the cortex, but many aspects of thalamocortical signaling remain unknown. Here, the authors reveal parallel non-overlapping thalamic pathways with distinct representations of tactile and decision-related information during a goal-directed sensorimotor task.

NATURE PUBLISHING GROUP2020

Conformable neural interfaces : from engineering stretchability at the micro-scale to translational applications

Florent-Valéry Coen

EPFL2022

EPFL2018