Visiting Speakers

Christian Bravo Rivera, PhD - Director of the Laboratory of Fear and Pleasure
President of NeuroBoricuas, University of Puerto Rico School of Medicine
Departments of Psychiatry and Anatomy & Neurobiology

 Jan 19, 2023 @ 4:00 p.m.

Reward is often present in risky environments, requiring individuals to weigh the benefits of rewards against the associated risks. There are individuals that are unable to choose an appropriate response during risky reward opportunities and thus exhibit extreme avoidance or risky behaviors that can severely impair quality of life or endanger people. It is therefore necessary to characterize how neurons mediate reward approach and threat avoidance conflict. Here, we adapted the platform-mediated avoidance conflict task (Bravo-Rivera et al 2014; Bravo-Rivera et al 2021), such that water-deprived mice could nose-poke for a light-signaled water reward and avoid a tone-signaled foot-shock by stepping onto a safety platform away from the reward port. Optogenetic activation of GABAergic neurons in the ventral pallidum invigorated reward approach at the expense of receiving shocks. Photometry recordings of glutamatergic neurons in the ventral pallidum and in the lateral habenula during conflict revealed that these structures promote avoidance and become inhibited during conflicted reward approach. These results suggest that a pallidal-habenula circuit mediates motivational conflict. We also compared behavioral conflict in male and female mice. Interestingly, females stepped on the platform earlier than males after tone onset and took longer to leave the platform after tone offset. Males received more shocks than females and received more water reward than females by the end conflict training. Moreover, females exhibited more tone-induced freezing and exhibited more frequent darting than males. These results suggest that females exhibit more avoidance behavior and less reward approach than males in the face of approach/avoidance conflict.

 Medical Center | Case Methods Room (1-9576)

Host: Benjamin Suarez-Jimenez

Shinho Cho, PhD - Research Associate, University of Minnesota Medical School
Center for Magnetic Resonance Research and Departments of Radiology

 Feb 28, 2023 @ 4:00 p.m.

Dr. Cho’s research aims to delineate the dynamic interaction and casual relationship between macro-, meso-, and microscopic-scale functional brain activity that underlies cognition, behavior, and clinical symptoms. He will present the functional relationship between the activity of subcortical brain regions and large-scale brain networks. Simultaneous deep brain stimulation and functional MRI (fMRI) in human and animal brains reveal that neuromodulation on deep brain structure (e.g., nucleus accumbens) altered not only the whole-brain network connectivity but influenced patients' cognition (e.g., mood). The following topic will illuminate the mesoscopic cortical layer and columnar organization that subserves visual orientation encoding in cats' primary visual cortex. The 9.4 Tesla fMRI and multiphoton optical imaging reveal the cortical layer-dependent orientation tuning property of hemodynamics response, reflected by vessel dilation and constriction. Dr. Cho will discuss the multimodal imaging (e.g., PET-MR) that bridges the gap of the dynamics between neurotransmitters (e.g., dopamine) and macroscopic brain networks; how the deficiency of neurotransmitters would impact brain and behaviors systematically. Overall, these findings and the integrated approach of different imaging modalities, behavioral assessment, and neuromodulation can characterize causal and correlational relationships in the hierarchical brain, providing a unique opportunity to understand the biological basis of cognition/behavior and neurologic/psychiatric disorders.

Flyer

 Medical Center | Upper Auditorium (3-7619)

Host: University of Rochester School of Medicine and Dentistry, Department of Neuroscience, and the Del Monte Institute for Neuroscience

Claudia I. Lugo-Candelas, PhD - Assistant Professor in Clinical Medical Psychology, Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center

 Mar 09, 2023 @ 4:00 p.m.

Sleep undergoes changes in pregnancy, becoming shorter in duration and more fragmented as the pregnancy progresses. While poor sleep in pregnancy has been associated to worse birth outcomes, whether poor sleep in pregnancy has long lasting effects on the development of the child has received little attention to date. Dr. Lugo-Candelas will present her work on sleep in the perinatal period, examining sleep as a possible mechanism via which adversity and risk for psychopathology is transmitted intergenerationally. Dr. Lugo-Candelas will present her lab’s work on the intergenerational sequalae of poor sleep in pregnancy, employing infant neuroimaging and biomarker work, as well as studies examining the social determinants of poor prenatal sleep.

 Medical Center | Case Method Rm (1-9576)

Host: University of Rochester School of Medicine and Dentistry
Department of Neuroscience and the Del Monte Institute for Neuroscience

David Holtzman, PhD - Barbara Burton and Reuben M. Morriss III Distinguished Professor Scientific
Director, Hope Center for Neurological Disorders, Department of Neurology Washington University School of Medicine

 Mar 13, 2023 @ 4:00 p.m.

APOE is the most important genetic risk factor for late-onset Alzheimer’s disease. In addition to its role in regulating amyloid-beta aggregation in the brain, recent evidence also suggests that it plays an important role in regulating the brain’s innate immune response in the setting of different brain pathologies. We have found that in a mouse model of tauopathy, APOE is required for tau-mediated neurodegeneration and this effect requires both the innate immune response (microglia) as well as interactions with microglia and the adaptive immune response (T cells). The role of T cells suggests that novel approaches to treatment are worth exploring for both primary and secondary tauopathies.

Michael Roberts, PhD - Michigan Neuroscience Institute Affiliate Assistant Professor, Department of Otolaryngology-Head and Neck Surgery

 Mar 20, 2023 @ 4:00 p.m.

The inferior colliculus (IC) is the midbrain hub of the central auditory system and an important site for computations related to speech processing and sound localization. With more than five times as many neurons as the lower auditory brainstem, the computational potential of the IC is immense, but the cellular and synaptic mechanisms underlying computations in the IC have remained largely unknown. Using a multifaceted approach, we recently identified VIP and NPY neurons as the first two molecularly identifiable neuron types in the IC. VIP neurons are glutamatergic, NPY neurons are GABAergic, and both project to long-range targets including the auditory thalamus. The discovery of VIP and NPY neurons has enabled us to identify fundamental new mechanisms that shape computations in the IC. This seminar will focus on two of these mechanisms. First, we will address how the expression of NR2D-containing NMDA receptors broadens the time window for synaptic integration in VIP neurons by enhancing the activation of NMDA receptors at resting membrane potential. These results have important implications for how VIP neurons and other IC neurons convert the temporal codes used extensively in the auditory brainstem to the rate codes that predominate in higher brain centers. Second, we will discuss how NPY neurons are poised to regulate network excitability in the IC through a combination of GABAergic and NPYergic signaling. Our data show that most glutamatergic neurons in the IC express NPY Y1 receptors and that activation of these receptors reduces recurrent excitation in local IC circuits. Together, these results provide important new insights into the varied ways that IC circuits can shape auditory processing.

Flyer

 Medical Center | Ryan Case Method Rm (1-9576)

Host: The Neuroscience Graduate Program

Sridhar S. Kannurpatti, PhD - Assistant Professor, Department of Radiology RUTGERS-New Jersey Medical School

 Mar 23, 2023 @ 4:00 p.m.

Mitochondria are important subcellular organelles which play a role in normal cellular signaling and energy metabolism. While most evidence comes from in vitro or ex-vivo studies, it makes human translation a challenge. Using pharmacological perturbation of mitochondrial Ca2+ uptake capacity (MC/UC) and functional imaging in vivo, the dynamic role of mitochondria in regulating both brain neural activity and neurovascular coupling has been identified. Currently, the feedback and feedforward hypotheses provide the biophysical basis for neurovascular coupling based on various in vivo messengers (eg., CO2, NO, K+, lactate, nNOS and PLA2). However, in vivo mitochondrial modulation and its effects on neural activity and functional imaging markers such as cerebral blood flow (CBF) and fMRI blood oxygen contrast (BOLD) responses, provide evidence for a unified hypothesis of MC/UC activity as a central mechanism of neurovascular coupling. As mitochondrial dysfunction is implicated in many neuropathologies, it is an obvious therapeutic target. Whether the central mechanism of MC/UC, which regulates neurovascular activity, can be harnessed as a therapeutic target will be presented. How translational preclinical imaging can help bridge gaps to easier clinical trial decision making will be discussed.

 Medical Center | Upper Auditorium (3-7619)

Host: University of Rochester School of Medicine and Dentistry, Department of Neuroscience and the Del Monte Institute for Neuroscience

Nian Wang, PhD - Assistant Professor, Radiology and Imaging Sciences
Indiana University

 Apr 06, 2023 @ 4:00 p.m.

Dr. Wang’s research focuses on developing novel quantitative MRI techniques and analysis methods on CNS and MSK systems. We have developed and implemented a 3D under-sampling strategy and sparse reconstruction for diffusion MRI at microscopic resolution. We have successfully pushed the spatial resolution of diffusion MRI close to cellular resolution, and this provides a solid technology foundation to investigate the whole-brain fiber orientation distributions, connectome, as well as tissue microstructure. We have refined the current algorithms for phase processing by solving the inverse problem of source-field relations to derive quantitative susceptibility mapping (QSM). This novel technique has been applied to different diseases, including multiple sclerosis, microbleeds, and Osteoarthritis. Dr. Wang’s will talk about how to get high-resolution MR images and the applications in Multiple sclerosis and Alzheimer’s disease.

 Medical Center | Upper Auditorium (3-7619)

Host: Department of Neuroscience and the Del Monte Institute for Neuroscience

Dean Salisbury, PhD - Director Clinical Neurophysiology Research Lab, Professor of Psychiatry, University of Pittsburgh

 May 18, 2023 @ 4:00 p.m.

Researchers have sought for more than 100 years for a lesion (or lesions) that might lead to schizophrenia, the major debilitating psychotic disorder. Early imaging modalities revealed enlarged ventricles, which imply reduced brain volumes, but no characteristic cortical pathology was identified. High-resolution structural magnetic resonance imaging (MRI) in the 1990s finally provided a tool to identify cortical volume loss in vivo. Volumetric studies revealed not only initial gray matter loss in temporal and frontal cortices, but progressive loss after the emergence of psychosis. Although frontal and temporal cortices showed more robust volume loss, eventually most of the cortex showed dendritic loss. Post-mortem work suggests this may be due to a loss of dendrites and synapses. Thought has focused on structural and functional dysconnectivity as primary culprits in schizophrenia, with the emerging concept of the disorder being one of circuitopathy. Decomposing source-activity from high-temporal resolution methods such as EEG and MEG projected to the cortical surface of individual MRI reconstructions into spectral components allows for functional and effective connectivity measures between areas. Our work focuses on the interplay between executive (frontal cortex) and visual (occipital) and auditory (temporal) cortices to examine circuitopathy in first-episode. Spectral connectivity indicates alpha-band and theta-band dysconnectivity between cortical areas are central deficits in psychosis, even early in disease course at the emergence of psychosis. Initial deficits in sensory processing provide degraded feedforward perceptual objects for cognition. This is compounded by faulty feedback executive modulation of sensory processes. Understanding circuit-level deficits may provide new avenues for targeted interventions, such as non-invasive brain stimulation.

 Medical Center | Ryan Case Method Rm (1-9576)

Host: Departments of Neuroscience and Psychiatry

Yoland Smith, PhD - Associate Research Professor, Neuropharmacology and Neurology Disease, Emory National Primate Research Center
Professor, Neurology, Emory

 Jun 01, 2023 @ 4:00 p.m.

Although our understanding of the pathophysiology of parkinsonism has grown significantly since the introduction of the “Direct and Indirect model” of basal ganglia circuits in the late 1980s, much remains to be known about the anatomical and functional neuroplastic changes of the basal ganglia-thalamocortical circuits that contribute to Parkinson’s disease pathophysiology. Most importantly, our understanding of synaptic and cellular changes induced by the progressive loss of nigrostriatal dopamine at the cortical and thalamic levels is still in its infancy. In this presentation, I will review recent findings from our laboratory that attempt at filling this knowledge gap using high-resolution electron microscopy and modern viral vector tracing approaches in a nonhuman primate model of Parkinsonism. Together with in vivo electrophysiology, PET imaging, and behavioral approaches, we believe that a better understanding of functional network dysfunctions can help develop and refine Parkinson’s disease therapeutic strategies.

 Medical Center | Ryan Case Method (1-9576)

Host: John Foxe

Steve Laviolette, PhD - Professor, Schulich School of Medicine & Dentistry, Western University, Canada

 Oct 23, 2023 @ 4:00 p.m.

With rising rates of maternal cannabis use, there is an urgent need to understand potential impacts of cannabinoid exposure on the developing fetal brain. In this presentation, we will present recent translational findings in our lab demonstrating that prenatal exposure to THC, the primary psychoactive compound in cannabis, can induce profound pathological impacts and neuropsychiatric risk elevation into adulthood, in exposed offspring. Interestingly, we have also found significant sex-selective effects on the male vs. female brains. We have recently reported (Sarikahya et al., Molecular Psychiatry, 2023) that the neural lipidome is especially impacted by prenatal cannabinoid exposure. In this presentation, we will present novel evidence that a dietary intervention with a high Omega-3 fatty acid formulation might be able to reverse or prevent many of the pathological effects of prenatal cannabinoid exposure. Finally, we will present new findings using a human cerebral organoid model of early brain development and present our findings on how exposure to cannabinoids can interact with schizophrenia risk factors at the neuronal, proteomic and transcriptomic landscapes during early brain development.

 Medical Center | K-207

Host: The Neuroscience Graduate Program