Sensorimotor regulation of facial expression - An untouched frontier.

Facial expression is a critical form of nonverbal social communication which promotes emotional exchange and affiliation among humans. Facial expressions are generated via precise contraction of the facial muscles, guided by sensory feedback. While the neural pathways underlying facial motor control are well characterized in humans and primates, it remains unknown how tactile and proprioceptive information reaches these pathways to guide facial muscle contraction. Thus, despite the importance of facial expressions for social functioning, little is known about how they are generated as a unique sensorimotor behavior. In this review, we highlight current knowledge about sensory feedback from the face and how it is distinct from other body regions. We describe connectivity between the facial sensory and motor brain systems, and call attention to the other brain systems which influence facial expression behavior, including vision, gustation, emotion, and interoception. Finally, we petition for more research on the sensory basis of facial expressions, asserting that incomplete understanding of sensorimotor mechanisms is a barrier to addressing atypical facial expressivity in clinical populations.

Three-dimensional histology reveals dissociable human hippocampal long-axis gradients of Alzheimer's pathology.

INTRODUCTION: Three-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without a magnetic resonance imaging (MRI) reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimer's disease. METHODS: Blockface photographs of brain hemisphere slices are used for 3D reconstruction, from which an MRI-like image is generated using machine learning. Histology sections are aligned to the reconstructed hemisphere and subsequently to an atlas in standard space. RESULTS: Path2MR successfully registered histological sections to their anatomic position along the hippocampal longitudinal axis. Combined with histopathology quantification, we found an expected peak of tau pathology at the anterior end of the hippocampus, whereas amyloid-beta (Aß) displayed a quadratic anterior-posterior distribution. CONCLUSION: Path2MR, which enables 3D histology using any brain bank data set, revealed significant differences along the hippocampus between tau and Aß. HIGHLIGHTS: Path2MR enables three-dimensional (3D) brain reconstruction from blockface dissection photographs. This pipeline does not require dense specimen sampling or a subject-specific magnetic resonance (MR) image. Anatomically consistent mapping of hippocampal sections was obtained with Path2MR. Our analyses revealed an anterior-posterior gradient of hippocampal tau pathology. In contrast, the peak of amyloid-beta (Aß) deposition was closer to the hippocampal body.

Three-dimensional histology reveals dissociable human hippocampal long axis gradients of Alzheimer's pathology.

INTRODUCTION: Three-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without an MRI reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimer's Disease. METHODS: Blockface photographs of brain hemisphere slices are used for 3D reconstruction, from which an MRI-like image is generated using machine learning. Histology sections are aligned to the reconstructed hemisphere and subsequently to an atlas in standard space. RESULTS: Path2MR successfully registered histological sections to their anatomical position along the hippocampal longitudinal axis. Combined with histopathology quantification, we found an expected peak of tau pathology at the anterior end of the hippocampus, while amyloid-ß displayed a quadratic anterior-posterior distribution. CONCLUSION: Path2MR, which enables 3D histology using any brain bank dataset, revealed significant differences along the hippocampus between tau and amyloid-ß.

Chemogenetic activation of an infralimbic cortex to basolateral amygdala projection promotes resistance to acute social defeat stress.

Tremendous individual differences exist in stress responsivity and social defeat stress is a key approach for identifying cellular mechanisms of stress susceptibility and resilience. Syrian hamsters show reliable territorial aggression, but after social defeat they exhibit a conditioned defeat (CD) response characterized by increased submission and an absence of aggression in future social interactions. Hamsters that achieve social dominance prior to social defeat exhibit greater defeat-induced neural activity in infralimbic (IL) cortex neurons that project to the basolateral amygdala (BLA) and reduced CD response compared to subordinate hamsters. Here, we hypothesize that chemogenetic activation of an IL-to-BLA neural projection during acute social defeat will reduce the CD response in subordinate hamsters and thereby produce dominant-like behavior. We confirmed that clozapine-N-oxide (CNO) itself did not alter the CD response and validated a dual-virus, Cre-dependent, chemogenetic approach by showing that CNO treatment increased c-Fos expression in the IL and decreased it in the BLA. We found that CNO treatment during social defeat reduced the acquisition of CD in subordinate, but not dominant, hamsters. This project extends our understanding of the neural circuits underlying resistance to acute social stress, which is an important step toward delineating circuit-based approaches for the treatment of stress-related psychopathologies.

Social Dominance Modulates Stress-induced Neural Activity in Medial Prefrontal Cortex Projections to the Basolateral Amygdala.

Stress is a contributing factor in the etiology of several mood and anxiety disorders, and social defeat models are used to investigate the biological basis of stress-related psychopathologies. Male Syrian hamsters are highly aggressive and territorial, but after social defeat they exhibit a conditioned defeat (CD) response which is characterized by increased submissive behavior and a failure to defend their home territory against a smaller, non-aggressive intruder. Hamsters with dominant social status show increased c-Fos expression in the infralimbic (IL) cortex following social defeat and display a reduced CD response at testing compared to subordinates and controls. In this study, we tested the prediction that dominants would show increased defeat-induced neural activity in IL, but not prelimbic (PL) or ventral hippocampus (vHPC), neurons that send efferent projections to the basolateral amygdala (BLA) compared to subordinates. We performed dual immunohistochemistry for c-Fos and cholera toxin B (CTB) and found that dominants display a significantly greater proportion of double-labeled c-Fos + CTB cells in both the IL and PL. Furthermore, dominants display more c-Fos-positive cells in both the IL and PL, but not vHPC, compared to subordinates. These findings suggest that dominant hamsters selectively activate IL and PL, but not vHPC, projections to the amygdala during social defeat, which may be responsible for their reduced CD response. This project extends our understanding of the neural circuits underlying resistance to social stress, which is an important step toward delineating a circuit-based approach for the prevention and treatment of stress-related psychopathologies.