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.

Using fMRI to Explore the Neural Basis of Anticipation After Implicit Distributional Learning

Danlei Chen, Carol Jew, Benjamin Zinszer, and Rajeev Raizada

Distributional learning research has established that humans can track the frequencies of sequentially presented stimuli in order to infer the probabilities of upcoming events (e.g., Hasher & Zacks, 1984). We hypothesize that as people learn this frequency information, probabilistically weighted representations of the next stimulus are activated in the brain prior to each trial. We present behavioral evidence that these weighted representations are measurable in the response time of the subsequent trial, and we propose a further experiment to directly test the neural hypothesis. In the behavioral experiment, twelve adult participants viewed photographs of faces, tools, and buildings while performing a simple classification task. Each of these categories reliably evokes stronger responses in specific sets of brain areas compared to other categories (Chao & Martin, 2000; Epstein & Kanwisher, 1998; Kanwisher, McDermott, & Chun, 1997), allowing us to measure the intensity of brain activity separately and in parallel for each category in the MRI scanner. The frequency of each category (60%, 30%, 10%) was counterbalanced across six different frequency distributions. Using a two-way (Frequency-by-Category) linear mixed-effects model, we compared response times for the stimuli in each distribution to see whether the anticipation of a more frequent category reduced the response time. Response times significantly decreased with greater frequencies (t(6123) = -7.289, p < .0005), indicating that participants anticipated the stimuli proportional to the probability of the category and thereby reduced response times for the more frequent categories. With this evidence of probabilistic anticipatory representations, we are now testing this effect using functional MRI. We hypothesize that anticipation of a category will evoke activity in category-specific regions proportional to the probability of that category. If the neuroimaging results are in line with this hypothesis, they will suggest that learned distributional information produces probabilistically weighted representations of possible outcomes.

Center-Embedded Sequence Learning In Children And Non-Human Primates

Abigail Haslinger, Stephen Ferrigno, Steven T. Piantadosi, and Jessica F. Cantlon

Recursion is a computational method that embeds elements inside one another, allowing for long-range relations in a sequence. It is important for a wide variety of human skills, including language, counting, and motor control. To date there has been no conclusive evidence that non-human animals can use center-embedded recursion, the type of recursion necessary for language acquisition. This has led some researchers to hypothesize that it is a uniquely human skill and possibly the limiting factor of human language ability. Here we investigate whether monkeys (rhesus macaques) and children (age 3-5 yrs.) can learn to apply center-embedded recursion in a sequencing task. Subjects were given a task in which they had to touch sets of pictures of brackets in recursive orders, e.g. [ < > ]. We then tested whether subjects could transfer this center-embedded strategy to novel stimuli. We found that children naturally use center-embedded recursion to order novel lists. This suggests that mastery of this task, and thus mastery of a component of human grammar, comes easily to children and develops very early in childhood. Although monkeys did not use center-embedded recursion at first, with additional training, they were capable of learning to use a center-embedded strategy and transfer this skill to novel stimuli. This suggests that center-embedded recursion is not a uniquely human ability and is therefore not likely the limiting factor of language.

No Natural Gender Differences in Children’s Earliest Quantitative Abilities

Kelsey Csumitta and Jessica Cantlon

Despite advances in gender equality within our society, men continue to be overrepresented in math-related careers. If there are “natural” differences in math ability between young boys and girls, these differences may impact later academic and career choices. Although some research has found that boys outperform girls on tests of math achievement in school, cultural influences may be contributing to these differences. Here we examined children’s quantitative processing abilities during early childhood prior to and during the first few years of formal school to provide data on whether and how early gender differences emerge in childhood. Over 400 children between 2 and 7 years were tested across two testing sites. First, we compared the performance of boys and girls on core numerosity perception during infancy and childhood and found that boys and girls performed similarly. Next, we compared boys and girls on verbal counting and knowledge of number word meanings during preschool. Boys and girls demonstrated similar levels of knowledge of number word meanings, but boys showed a slight advantage on culturally-learned memorization. Finally, we compared boys and girls on school-based tests of math achievement during the first few years of formal schooling. Boys and girls performed equally on mathematical concepts that draw on untrained, acquired knowledge, but boys performed slightly better on questions that rely on concepts that are formally taught in school. None of the differences between boys and girls approached one standard deviation. Overall the data show no intrinsic early childhood gender differences in quantitative reasoning, but some negligible gender differences in quantitative concepts that are culturally trained. This suggests that cultural influences may account for the gender discrepancy seen in math-related careers.