Projections from the Temporal Cortex to the Basal Nucleus of the Amygdala in the Macaque

Ashley Bui, Sarah Friedman, Emily A. Kelly, and Julie L. Fudge

The amygdala is a complex brain structure involved in the emotional coding of complex sensory stimuli. In primates, including humans, visual information in the form of faces is one of the most important drivers of amygdala activity. We asked whether information from the temporal cortex – where visual information is hierarchically processed – shows a particular pattern of inputs to one of the main amygdala nuclei, the basal nucleus (BA). Following injections of neuronal tracers into the BA in four monkeys, we examined the temporal cortex for retrogradely labeled cells using immunocytochemistry and a neuron tracing software (Neurolucida). The most ventromedial injection in the BA had the most restricted distribution of labeled cells, found mainly in the entorhinal cortex. A slightly more dorsal injection resulted in additional dense labeling in the perirhinal cortex and moderate numbers of labeled cells in the inferotemporal cortex (TE). Increasingly dorsal injections resulted in heavy concentrations of labeled cells in the entorhinal and perirhinal cortices and TE, with additional labeled cells in the superior temporal gyrus (STG) and sulcus (STS). There is a topography of temporal cortical inputs to the BA with the most ventral regions receiving restricted inputs from entorhinal cortex. Inputs from perirhinal cortex, and eventually, TE, and STS/STG progressively contribute additional information to more dorsal BA sites. The entorhinal cortex plays a role in episodic memory, which is the memory of highly personal detailed information. The perirhinal cortex is intimately linked to the entorhinal cortex, and is implicated in visual place recognition. TE and adjacent STG and STS are more directly related to perception of ongoing visual information such as objects and faces. While memory-based information from entorhinal and perirhinal cortex, respectively, influence the entire BA, the dorsal regions are specialized in receiving inputs of faces and objects in the immediate environment.

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Reciprocal Effects Of Glymphatic Function And The Experimental Autoimmune Encephalomyelitis (EAE) Model Of Multiple Sclerosis

Hanna Vinitsky, Iben Lundgaard, Shane O’neil, Wei Wang, Ben Reeves, Ezra Yang, Steven Goldman, Maiken Nedergaard Iben Lundgaard 

Multiple Sclerosis (MS) is an autoimmune disease targeting myelin in the central nervous system. Lesions in MS patients and in the experimental autoimmune (EAE) model of MS are characterized by immune cell infiltration, often forming peri-vascular cuffing around blood vessels. Here we used the EAE mouse model of MS and investigated glymphatic function dynamics using a fluorescent cerebrospinal fluid (CSF) tracer. The glymphatic system is a brain-wide clearance system using peri-vascular pathways for transport. We found that glymphatic influx to the brain was reduced and influx to the spinal cord was severely diminished. The distribution of CSF tracer was inversely correlated with the number of lesions, suggesting that EAE tissue pathology affects the glymphatic system in acute and chronic disease. Intriguingly, inhibition of the glymphatic function using acetazolamide and cisterna magna puncture (CMP) in the pre-symptomatic phase significantly ameliorated EAE clinical symptoms. This shows that glymphatic function is affected in EAE, but that disease progression might be aided by the glymphatic system in the early phase. This preliminary data suggests that targeting the glymphatic system in the early phase of MS might be a novel mechanism to curb disease.

Optogenetic Control of ROS Production in C. elegans

Alicia Wei, Keith Nehrke and Andrew Wojtovich 

Reactive Oxygen Species (ROS) can be detrimental or may lead to beneficial adaptive responses. The factors that distinguish between these outcomes are not readily determined using existing techniques. Here, we have developed a novel C. elegans model to study the effects of ROS in a physiologic context using a combination of CRISPR/Cas9 gene editing and optogenetics. Mitochondria are a main source of ROS and are central to cell death and adaptation to stress. We used cutting edge genetic techniques to fuse components of the mitochondrial respiratory chain to proteins that can produce ROS in response to light. MiniSOG produces singlet oxygen, which has the singular capacity to illicit damage, while SuperNova creates superoxide, which we predict may be beneficial in limited amounts. We fused miniSOG to complex II of the mitochondrial respiratory chain in C. elegans. The strain exhibited light-sensitive loss of complex II activity and the worms exhibited adverse reactions to light under conditions of mild stress such as, paraquat, an ROS generator or FCCP, a protonophore. In contrast, the strain expressing the SuperNova fusion had no adverse reaction to light and the conditions of mild stress when coupled with light. Future experiments will be necessary to determine whether light is in fact beneficial in this strain, as we hypothesize. With these constructs, we will be able to study the complex II of the mitochondrial respiratory chain ROS microdomains.

Development of a Sciatic Nerve Schawannoma Model for Surgical Stimulation

Shivali Mukerji, Jonathan Stone and G. Edward Vates

Neurosurgery is a field that requires extreme precision and skill and just like many other medical fields, is currently trying to find solutions to undertrained residents. Surgical education relies on training in the operating room and combined with long working hours, exhaustion this can threaten patient safety, increase operative times, and produce an entire generation of under-trained residents. The aim of this research project is to develop a learning tool that is inexpensive and yet effective in it’s use. Using 3D printed molds and polymer hydrogels, we aim to create an anatomically accurate representation of a sciatic nerve schwannoma extraction surgery. A schwannoma is a benign nerve tumor made of Schwann cells that tends to push the nerve in the affected area aside and if not removed in a timely manner, can cause debilitating pain. Using Poly Vinyl Alcohol (PVA) hydrogels and imaging from patients, layers of the thigh and the various components such as the nerve sheath along with the tumor are created. To replicate the functioning of a nerve, conductive yarn material is integrated into the nerve sheath to replicate nerve activity on stimulation and damage. PVA is selectively cross linked to mimic different tissue structures and capillaries containing blood are added to the dermis to mimic bleeding. This complete model includes all the components of a schwannoma removal surgery from delicate dissection of anatomical planes, identification of proximal and distal nerve ends, subcapsular dissection of the tumor, and multi-layer closure. The objective of this model is two fold- 1) to be an effective learning tool for residents entering the field thereby giving way to future models of more common surgeries and improving confidence amongst residents. T 2) The model provides residents the opportunity to become familiar with an otherwise rare disease.