Events

Mar 01, 2017
12:00 PM
Bldg 149 Room 2204

Abstract:
Pathways from cortical and subcortical structures give the specialized sectors of the prefrontal cortex a panoramic view of the sensory environment and the internal milieu of motives and drives. The prefrontal cortex also receives privileged information from the output of the basal ganglia and cerebellum, and along with the amygdala, innervates widely the inhibitory thalamic reticular nucleus which gates the entire thalamo-cortical system. Specialized pathways from the anterior cingulate cortex, to inhibitory neurons in lateral prefrontal cortex, and from the posterior orbitofrontal cortex to the inhibitory intercalated masses of the amygdala are poised to control attention to salient stimuli and eliminate distracters. Connections are strongly related to the systematic structural variation of the cortex that can be traced to development. The patterns of connections of the specialized prefrontal sectors suggest the sequence of information processing for cognition, emotion and executive control, and point to nodes of vulnerability in psychiatric and neurologic diseases.

About the speaker
Helen Barbas studied neuroscience at McGill University (Ph.D) and at Harvard Neurological Unit, Beth Israel Hospital (postdoctoral), before moving to Boston University and School of Medicine, where she is now Professor. She established and directs the Neural Systems Laboratory at Boston University, funded by grants from the National Institutes of Health (NINDS and NIMH), the National Science Foundation, and Autism Speaks. Her research focuses on the prefrontal cortex and the organization and synaptology of prefrontal pathways associated with cognitive, mnemonic and emotional processes in primates. Research focuses on the interaction of pathways with both excitatory and inhibitory neurons in the cortex and subcortical structures. Quantitative data on connections are used to uncover principles that underlie their strength, presence, absence and laminar pattern through computational analyses and modeling. Some publications from the laboratory are found at: http://www.bu.edu/neural/
e-mail: barbas@bu.edu

Mar 22, 2017
12:00 PM

 

Abstract:

Metabotropic glutamatergic receptors have received a lot of attention in the past decade due to their ability to mediate mood and cognitive processes in animal models, and due to the emerging role of glutamate dysfunction in psychiatric disorders. We designed several experiments to determine the role of mGluR5 in mood and trauma disorders. Our data show that although mGluR5 ligands do not compete directly with the glutamate site on mGluR5, there is an inverse association between mGluR5 availability and glutamate. Further, contrary to the previously published study in younger adults, our large study in MDD suggests that mGluR5 is not involved in mood symptoms of depression, but that rapid downregulation of mGluR5 is associated with a reduction in anxiety symptoms. Additional data suggest upregulation of mGluR5 in individuals with PTSD, with individuals with more symptomatology having higher receptor levels. In parallel, we conducted postmortem work in PTSD, examining mGluR5 and glucocorticoid markers that suggest upregulation of mGluR5 due to a combination of upregulated SHANK-1 and downregulation of GC proteins in PTSD. Obtaining these markers in parallel with PET imaging work will greatly elucidate our understanding of mGluR5 involvement in PTSD. The second portion of the talk will focus on our novel examinations of synaptic density imaging in vivo by imaging synaptic vesicle glycoprotein (SV2A) -an excellent marker of synaptic density in the brain. Initial rodent and human work show reductions in synaptic density due to stress/depression, with the extent of the reduction being associated with affective and cognitive dysregulation in individuals with MDD. Studies are ongoing to examine the extent of this reduction in MDD and PTSD, and its association to symptomatology. 

 

About the Speaker

Irina received her PhD in clinical neuropsychology from UConn in 2005 and came to Yale for postdoctoral fellowship in molecular neuroimaging of addiction disorders. From then on, she was hooked on SPECT and PET work, and with the receipt of K01 award in 2011 she has focused on elucidating the molecular changes associated with mood and comorbid disorder. The earlier stage of her career was dedicated to the acetylcholinergic system and she developed a novel paradigm to interrogate the cholinergic system in vivo in a human. For this, she won recognition from SNMMI and ACNP societies. Presently, their group is using this paradigm to investigate changes in acetylcholinergic system associated with smoking and cessation. Receipt of NARSAD and DANA awards allowed her to start a series of projects with mGluR5. In collaboration with Christine DeLorenzo, she has examination the effects of glutamate surge on mGluR5 in vivo as well as provided elucidation for the interesting same-day test retest studies at the mGluR5 site. She also received R01 from NIMH to examine mGluR5 as a biomarker of bipolar depression (versus unipolar) and whether it underlies the positive emotion dysregulation observed in bipolar disorder. With the addition of the PTSD work in collaboration with the VA, she likely has the largest mGluR5 data set. Most recently, Irina took advantage of the UCB-J development – a radioligand believed to provide indirect quantification of synaptic density – and has extended her work to look at synaptic density changes associated with mood and trauma disorders, both in animal models of stress as well as in vivo in humans.