BEGIN:VCALENDAR
VERSION:2.0
PRODID:icalendar-ruby
CALSCALE:GREGORIAN
X-WR-CALNAME:NeuroLunch: Miranda Dawson (Fan Lab) & Raleigh Linville (Heima
 n Lab)
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20260907T234153Z
UID:tag:localist.com\,2008:EventInstance_52023852208015
DTSTART:20260504T160000Z
DTEND:20260504T170000Z
DESCRIPTION:Title: Machine learning-guided rhodopsin engineering enables se
 nsitive all-optical voltage imaging and optogenetics\n\nSpeaker:Miranda Da
 wson (Fan Lab)\n\nAbstract:  Understanding how neural circuits change duri
 ng learning and disease requires tools that can measure fast synaptic volt
 age signals with high spatial and temporal resolution. Genetically encoded
  voltage indicators (GEVIs) enable optical recording of membrane potential
  dynamics from genetically defined neurons\, but current sensors lack the 
 sensitivity and robustness needed to reliably resolve subthreshold synapti
 c events on single trials in vivo during behavior. We develop and apply ne
 xt-generation rhodopsin-based GEVIs optimized for brightness\, voltage sen
 sitivity\, and kinetics. Using a machine learning-guided protein engineeri
 ng framework\, candidate indicators are computationally prioritized across
  multiple performance parameters and experimentally benchmarked using all-
 optical electrophysiology in neuronal cultures. Top-performing variants ar
 e integrated with two-photon optogenetic approaches to establish an all-op
 tical platform capable of resolving unitary synaptic excitation and inhibi
 tion in intact neural circuits during behavior. By enabling direct optical
  measurement of synaptic signaling during behavior\, this work overcomes a
  critical technical barrier in systems neuroscience and provides new tools
  for investigating circuit plasticity mechanisms underlying learning\, mem
 ory\, and neurological disorders.\n\nTitle: Multiomic Dissection of Striat
 al Subregion and Cell Type Vulnerabilities in Huntington’s Disease\n\nSp
 eaker: Raleigh Linville (Heiman Lab)\n\nAbstract: The striatum is critical
  for decision-making\, movement\, and reward processing\, functions achiev
 ed through subregional cellular and molecular specialization. Striatal cel
 l types and subregions are differentially implicated in neurodegenerative 
 and neuropsychiatric disorders\, yet the mechanisms underlying these vulne
 rabilities remain poorly understood. Using single-nucleus RNA sequencing a
 cross 109 human samples spanning dorsal and ventral striatum\, we present 
 a comprehensive atlas of striatal subregional neuronal specialization incl
 uding characterization of transcriptional gradients along the dorsolateral
 -ventromedial axis. Harnessing this atlas\, we investigate the molecular b
 asis of the progressive and selective loss of medium spiny neurons (MSNs) 
 with a characteristic dorsal-to-ventral gradient\, a hallmark of HD neurop
 athology. Through paired single-cell transcriptomic and somatic HTT CAG re
 peat expansion measurements in human postmortem tissue\, we demonstrate th
 at within the same HD brains\, the dorsal striatum displays greater MSN lo
 ss\, transcriptional dysregulation\, and HTT CAG repeat instability relati
 ve to the ventral striatum. Furthermore\, dorsolateral MSN identity predic
 ts CAG repeat length-dependent gene programs\, linking single-cell resolut
 ion measurements to the established dorso-ventral axis of HD neuropatholog
 y. Lastly\, applying both single-cell and spatial transcriptomics\, we cha
 racterize a rare population of MSNs that emerge in HD and are marked by ab
 errant gene expression consistent with loss of polycomb repressive complex
  function\, intranuclear mutant HTT inclusions\, and engagement of multifa
 ceted compensatory programs. Together\, our findings establish a framework
  for understanding how striatal cell type identity and subregional positio
 n shape vulnerability in HD\, with implications for early-stage therapeuti
 c targeting.
GEO:42.362302;-71.091766
LOCATION:Building 46\, 3310
SUMMARY:NeuroLunch: Miranda Dawson (Fan Lab) & Raleigh Linville (Heiman Lab
 )
URL;VALUE=URI:https://calendar.mit.edu/event/neurolunch-kohleman-swift-fan-
 lab-raleigh-linville-heiman-lab
CATEGORIES:Conferences/Seminars/Lectures
END:VEVENT
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